Showing papers on "Angiotensin II published in 1975"
TL;DR: Although ACE was first considered to be a carboxypeptidase-type enzyme, its actions go beyond cleaving dipep-tides from the free C-terminal end of peptide substrates, some of the basic properties of this enzyme remain unexplained.
Abstract: Many of the properties of angiotensin I converting enzyme or kininase II (ACE) have been discussed in extenso in the literature. The mode of action of ACE inhibitors has been studied in experimental animals and used clinically in millions of patients. The relatively few side effects have also been amply scrutinized. Nevertheless, some of the basic properties of this enzyme remain unexplained. For instance, although ACE was first considered to be a carboxypeptidase-type enzyme (peptidyl dipeptidase or dipeptidyl carboxypeptidase) (1,2) its actions go beyond cleaving dipep-tides from the free C-terminal end of peptide substrates. ACE inactivates substance P in spite of its blocked C-terminus, primarily by releasing the C-terminal tripeptide Gly-Leu-Met-NH2 (3). The blocked C-terminal tripep-tide, Arg-Pro-Gly-NH2, is also released from the luteinizing hormone releasing hormone (LHRH) (A). ACE, surprisingly, also cleaves the protected the N-terminal tripeptide
548 citations
TL;DR: Results show that urinary prostaglandins may originate from the kidney, indicating that renally synthesized prostag landins diffuse or are excreted into the tubule, and have potential as a tool to delineate renal prostaglanders physiology and pathology.
Abstract: Human urine was analyzed by mass spectrometry for the presence of prostaglandins. Prostaglandin E2 and F2alpha were detected in urine from females by selected ion monitoring of the prostaglandin E2-methylester-methoxime bis-acetate and the prostaglandin F2alpha-methyl ester-Tris-trimethylsilylether derivative. Additional evidence for the presence of prostaglandin F2alpha was obtained by isolating from female urine an amount of this prostaglandin sufficient to yield a complete mass spectrum. The methods utilized permitted quantitative analysis. The origin of urinary prostaglandin was determined by stimulating renal prostaglandin synthesis by arachidonic acid or angiotensin infusion. Arachidonic acid, the precursor of prostaglandin E2, when infused into one renal artery of a dog led to a significant increase in the excretion rate of this prostaglandin. Similarly, infusion of angiotensin II amide led to a significantly increased ipsilateral excretion rate of prostaglandin E2 and F2a in spite of a simultaneous decrease in the creatinine clearance. In man, i.v. infusion of angiotensin also led to an increased urinary eliminiation of prostaglandin E. These results show that urinary prostaglandins may originate from the kidney, indicating that renally synthesized prostaglandins diffuse or are excreted into the tubule. Thus, urinary prostaglandins are a reflection of renal prostaglandin synthesis and have potential as a tool to delineate renal prostaglandin physiology and pathology.
494 citations
TL;DR: Despite the marked increases in -±E, absolute rates of proximal tubule fluid reabsorption, on the average, were unchanged by these hormones due to the opposing effects of marked decreases in efferent arteriolar plasma flow rate and, to a lesser extent, increases in peritubular capillary hydraulic pressure.
Abstract: In 26 Wistar rats with surface glomeruli, the determinants of glomerular ultrafiltration and peritubular capillary uptake of proximal reabsorbate were studied before and during intravenous infusions of norepinephrine or angiotensin II Regardless of whether renal perfusion pressure (AP) was permitted to increase, both hormones produced elevations in single nephron filtration fraction due to declines in glomerular plasma flow with little change in nephron glomerular filtration rate The resulting large increases in the efferent arteriolar oncotic pressure, piE, were accompanied by equivalent increases in the mean glomerular transcapillary hydraulic pressure difference, deltaP Equality of piE and deltaP, denoting filtration pressure equilibrium, obtained before and during infusion of either hormone Por both hormones, when elevations in AP were allowed, marked and roughly proportional increases in the resistance to blood flow through single afferent and efferent arterioles occurred, whereas when increases in AP were prevented by partial aortic constriction increases in resistance were confined primarily to the efferent arteriole Tespite the marked increases in piE, absolute rates of proximal tubule fluid reabsorption, on the average, were unchanged by these hormones due to the opposing effects of marked decreases in efferent arteriolar plasma flow rate and, to a lesser extent, increases in peritubular capillary hydraulic pressure
336 citations
TL;DR: Findings indicated that angiotensin ii probably caused hypertension in the "responders," and one "nonresponder" had renal vein levels of plasma renin activity suggestive of angiotENSinogenic hypertension.
Abstract: The possibility has been explored of using a specific angiotensin II antagonist, saralasin (P-113, 1-sar-8-ala-angiotensin II) to recognize patients whose hypertension depends upon excessive angiotensin II activity. Among 60 hypertensive patients, saralasin infusion reduced blood pressure in 16 "responders," but not in 44 "nonresponders." The "responders" had the following findings: elevated plasma renin activity in renal vein (or veins) or peripheral veins or both (16 of 16); reduced renal blood flow, shown by arteriography, isotopic studies or pyelography (15 of 16), or progressive azotemia (one of 16); and reduction in blood These findings indicated that angiotensin II probably caused hypertension in the "responders." One "nonresponder" had renal vein levels of plasma renin activity suggestive of angiotensinogenic hypertension. Since hypertension was invariably angiotensinogenic when it was reduced by saralasin and, with one possible exception, was never angiotensinogenic in "nonresponders," t...
276 citations
TL;DR: In this paper, the authors test the hypothesis that angiotensin II releases antidiuretic hormone (ADH) after injection into ventricular cerebrospinal fluid, conscious adult male Sprague- Dawley rats with a lateral cerebroventricular cannula received an intraventricular injection of 0, 10, 50, or 100 ng angiotENSin II Trunk blood was collected 90 seconds later for radioimmunoassay of ADH.
Abstract: To test the hypothesis that angiotensin II releases antidiuretic hormone (ADH) after injection into ventricular cerebrospinal fluid, conscious adult male Sprague- Dawley rats with a lateral cerebroventricular cannula received an intraventricular injection of 0, 10, 50, or 100 ng angiotensin II Trunk blood was collected 90 seconds later for radioimmunoassay of ADH Plasma ADH, pg/ml (mean ± SE), for the four dose levels were 28 ± 07, 96 ± 25, 226 ± 56 and 250 ± 50, respectively The increases produced by angiotensin were statistically significant (p < 005) Plasma ADH of the 10 ng group was intermediate between control and the two highest angiotensin doses (p < 005), suggesting a dose-response relationship These data provide direct evidence that angiotensin releases ADH by central mechanisms
268 citations
TL;DR: Immunoreactive material resembling prostaglandin E accumulates in the medium of cultured human umbilical vein endothelial cells and may be important in platelet-dependent thrombotic phenomena, and in local control of vascular permeability and tone in vivo.
Abstract: Immunoreactive material resembling prostaglandin E accumulates in the medium of cultured human umbilical vein endothelial cells. Prodcution is inhibited by indomethacin and stimulated by angiotensin II. Prostaglandin secretion by endothelium may be important in platelet-dependent thrombotic phenomena, and in local control of vascular permeability and tone in vivo.
262 citations
TL;DR: The hypothesis of a periventricular receptor site for angiotensin is supported and it is suggested that systemically generated ang Elliotensin and angiotENSin endogenous to the brain may use the ventricular route as a means of access to the sensitive perivocentular site.
243 citations
TL;DR: It is concluded that malignant vasculitis in this model is preceded by hypertension associated with sodium and water retention and is accompanied by negative sodium balance, decreases in body weight, falling blood pressure, and hemoconcentration without demonstrable participation of the renin-angiotensin system or the renal catecholamines.
Abstract: The evolution of malignant hypertension was studied under metabolic balance conditions in 11 uninephrectomized rats given deoxycorticosterone acetate and 1% NaCl as drinking water. Changes in sodium and potassium balance were related to changes in blood pressure, plasma renin activity, hematocrit, and kidney histology. After 3-4 weeks of steadily positive sodium balance accompanied by continuously increasing blood pressure up to 185 plus or minus 19 (SE) mm Hg, periods of sodium loss accompanied by evidence of hemoconcentration were observed marking the onset of the malignant phase as defined by the development of fibrinoid necrosis in the kidney. Plasma renin activity remained markedly suppressed both at the fourth week (0.33 plus or minus 0.02 ng/ml hour-1) when the sodium balance was positive and the kidney biopsy negative and at the end of the experiment (0.35 plus or minus 0.36 ng/ml hour-1) when the sodium balance was negative and the kidney histology revealed malignant vasculitis. Infusion of the angiotensin II inhibitor 1-Sar-8-Ala-angiotensin II consistently failed to affect blood pressure, and the kidney tissue norepinephrine level was reduced (0.054 plus or minus 0.01 mug/g) compared with the control level (0.132 plus or minus 0.02 mug/g). We conclude that malignant vasculitis in this model is preceded by hypertension associated with sodium and water retention and is accompanied by negative sodium balance, decreases in body weight, falling blood pressure, and hemoconcentration without demonstrable participation of the renin-angiotensin system or the renal catecholamines.
211 citations
TL;DR: The data support an important role for physiologic changes in extracellular potassium concentration in the control of ald testosterone secretion and indicate that interpretation of studies assessing acute changes in plasma aldosterone must carefully consider minor simultaneous changes in Plasma potassium levels.
Abstract: The present study was performed to assess the sensitivity of the renin-angiotensinaldosterone axis to small changes in plasma potassium concentration within the physiologic range. Small increments in potassium levels were accomplished by graded constant infusions of potassium chloride over 2 h (0.17 meq/min; 0.33 meq/min; 0.5 meq/min) in 8 normal subjects on a 10 meq sodium-100 meq potassium intake. Plasma levels of aldosterone, renin activity, angiotensin II, cortisol, potassium and sodium were measured at frequent intervals. There were no significant changes observed in plasma sodium, renin activity or angiotensin II levels while cortisol levels declined in the expected diurnal pattern. During the 0.17 meq/min (10 meq/h) infusion potassium levels did not increase significantly until 120 min while plasma aldosterone levels rose significantly at 30-60 min. The mean increment above control during the lowest infusion rate was 0.2 meq/liter (5%) for plasma potassium and 13 ng/100 ml (46%) for plasma aldoster...
163 citations
TL;DR: Impaired cardiovascular reactivity in patients with chronic liver disease could predispose them to circulatory failure after haemorrhage or surgery and should be considered when prescribing drugs which affect autonomic activity.
162 citations
TL;DR: The synthesis and degradation of several potent vasoactive substances influencing coronary resistance were characterized in the isolated perfused rabbit heart and a prostaglandin E2-like substance appeared to be the endogenous mediator of the coronary vasodilation produced by bradykinin and angiotensin II (All).
Abstract: In the present study, the synthesis and degradation of several potent vasoactive substances influencing coronary resistance were characterized in the isolated perfused rabbit heart. Prostaglandin synthetase activity, angiotensin converting enzyme activity, and bradykininase activity (without angiotensinase) were observed. A prostaglandin E2-like substance appeared to be the ednogenous mediator of the coronary vasodilation produced by bradykinin and angiotensin II (AII). (1) The concentration of this prostaglandinlike substance in the coronary venous effluent was directly proportional to the concentration of the coronary vasocilator stimulus (bradykinin or AII). (2) The prostaglandinlike substance released and the coronary dilation produced by the agonists correlated temporally and quantitatively. (3). Abolition of cardiac biosynthesis of the prostaglandinlike substance by indomethacin also abolished the decrease in coronary resistance produced by the agonists. AII, the most potent naturally occurring vasoconstrictor substance, produced a paradoxical coronary vasodilation because it stimulated cardiac prostaglandin biosynthesis, but the direct coronary vasoconstrictor action of AII could be readily unmasked by indomethacin, which blocks prostaglandin synthesis. The nonapeptide SQ-20881 blocked cardiac biosynthesis of AII (from angiotensin I) and enhanced the coronary vascular effects of bradykinin by interfering with bradykininase activity. Similarly, the AII-receptor antagonist, 1-Sar-8-Ile-AII, blocked the coronary vascular effect of AII.
TL;DR: The ability of large doses of exogenous angiotensin II to cause widespread multifocal microscopic myocardial necrosis in the rabbit has been confirmed and cardiac attacks in these five patients all occurred during or shortly after procedures, such as sodium-depleting dialysis, renal artery surgery, or diazoxide administration, known to cause increase in plasma concentrations of renin and angiotensor II.
TL;DR: The view that the decrease in angiotensin II pressor activity during salt deprivation is the result of a prior occupancy of receptor sites by endogenous hormone is supported, and a change in the number or the affinity of receptors consequent to changes in sodium balance need not be postulated to explain the phenomenon.
Abstract: The pressor responsiveness to angiotensin II and norepinephrine was examined in rats before and during blockade of coverting enzyme activity with the nonapeptide SQ 20881. Responses to angiotensin II were impaired by sodium deprivation but enhanced by sodium loading or bilateral nephrectomy. During the period of converting enzyme blockade, a twofold increase in the angiotensin II pressor response was observed in the salt-restricted rats, whereas only a small change occurred in the salt-loaded rats. Infusion of the inhibitor produced a profound fall in the blood pressure of the salt-depleted rats with a relatively minor fall in the sodium-loaded rats. Norepinephrine pressor responses were slightly potentiated in the salt-restricted rats after administration of SQ 20881, but no change occurred in the salt-loaded or the nephrectomized rats. These observations support the view that the decreased angiotensin II pressor activity during salt deprivation is the result of a prior occupancy of receptor sites by endogenous hormone. Therefore, a change in the number or the affinity of receptors consequent to changes in sodium balance need not be postulated to explain the phenomenon.
TL;DR: It is concluded that sodium nitroprusside acts on excitation-contraction coupling predominantly in tonic smooth muscle by interfering with both the influx and the intracellular activation of calcium.
Abstract: 1.
Sodium nitroprusside is a potent relaxant of smooth muscles with a predominantly tonic response, e.g. rat aorta contracted by noradrenaline angiotensin II, Phe2-Lys8-vasopressin, BaCl2, or KCl, and guinea-pig tracheal smooth muscle contracted by carbachol.
2.
Smooth muscle preparations from the splanchnic region and with varying degrees of phasic contractility are less sensitive and develop tachyphylaxis (portal vein, duodenum of the rat) or are unresponsive to sodium nitroprusside (vas deferens, uterus of the rat).
3.
Cardiac auricles of the guinea pig are not affected by sodium nitroprusside in either frequency or amplitude of spontaneous contractions.
4.
Sodium nitroprusside causes a parallel shift of the dose-response curve of rat aorta to noradrenaline to the right and reduces the maximum response.
5.
The drug has no blocking or stimulant effect on α-or β-adrenoceptors, respectively.
6.
Sodium nitroprusside inhibits the contractile response of calcium-depleted depolarized rat aorta to extra-cellular calcium. Like verapamil, it inhibits the increment in 45calcium uptake of rabbit aorta elicited by K+. Sodium nitroprusside significantly reduces 45calcium binding by microsomes prepared from rabbit aorta.
7.
Rabbit aorta was incubated with lanthanum chloride to prevent calcium influx; sodium nitroprusside reduced the maintained rapid contraction phase in response to noradrenaline which is believed to be based on the intracellular activation of calcium.
8.
In rat aorta, cellular cAMP and ATP levels were not found to be affected by the drug.
9.
Rabbit aorta, “skinned” by glycerination, is unresponsive to sodium nitroprusside.
10.
It is concluded that sodium nitroprusside acts on excitation-contraction coupling predominantly in tonic smooth muscle by interfering with both the influx and the intracellular activation of calcium.
TL;DR: The data indicate that two- Kidney Goldblatt hypertension is initially renin dependent but subsequently becomes sodium volume dependent in a way similar, although more protracted, to that already described for one-kidney Gold Blatt hypertension.
Abstract: An angiotensin II inhibitor was administered to rats with two-kidney Goldblatt hypertension. The inhibitor produced a marked drop in blood pressure after 5 weeks but no significant change after 15 weeks of hypertension. However, even after 15 weeks of hypertension, following sodium depletion by either diuretics or a low sodium diet, the animals again became renin dependent as readministration of the inhibitor induced a significant fall in blood pressure. The data indicate that two-kidney Goldblatt hypertension is initially renin dependent but subsequently becomes sodium volume dependent in a way similar, although more protracted, to that already described for one-kidney Goldblatt hypertension.
TL;DR: Lesions of the subfornical organ (SFO) severely attenuated drinking induced by injections of angiotensin II into the lateral ventricles, but a few days later a recovery of the drinking response is observed.
Abstract: Lesions of the subfornical organ (SFO) severely attenuated drinking induced by injections of angiotensin II into the lateral ventricles, but a few days (4 to 14) later a recovery of the drinking response is observed. A possible explanation for this is that other dipsogenic sites are involved which are beyond the interventricular foramen and that SFO lesions produce an obstruction by edema or debris at the foramen which blocks access of cerebrospinal fluid-borne angiotensin to those sites. This hypothesis is supported by tracer studies and by direct injection into the third ventricle of SFO-lesioned animals. Other studies reported implicate the anteroventral third ventricle as a likely site for angiotensin receptors.
TL;DR: Peptide hormones, luteinizing hormone, follicle-stimulating hormone and angiotensin II, iodinated with lactoperoxidase or lactoperxidase sorbent for radioimmunoassays reacted better than peptide hormones iodination with chemical oxidants and remained unaltered during storage.
TL;DR: This formulation of the angiotensin reaction sequence and the effects of its individual congeners permits simple explanations for previously confusing data, such as the inability of immunization and anti-angiotens in II to prevent aldosterone responses, and “the paradoxical preservation of adrenal responsiveness in Bartter's syndrome.
Abstract: Evidence is reviewed that three and possibly four peptides formed from renin substrate have biological activity that merits their recognition as agonists. The decepeptide angiotensin I affects sites in the central nervous system and adrenal medulla. The octapeptide angiotensin II affects vascular and cardiac sites that mediate acute pressor responses, and also causes direct feedback inhibition of renin release. The heptapeptide (des-asp-1)-angiotensin II ("angiotensin III") stimulates aldosterone release.. It may exert its effects intracellularly at the adrenal glomerulosa and other sites. The fourth candidate is the (des-asp-1)-angiotensin I nonapeptide, but nothing is known of its activity or circulating levels. This formulation of the angiotensin reaction sequence and the effects of its individual congeners suggests several experiments. It also permits simple explanations for previously confusing data, such as the inability of immunization and anti-angiotensin II to prevent aldosterone responses, and the paradoxical preservation of adrenal responsiveness in Bartter's syndrome.
TL;DR: It is concluded that among the many functions of dopaminergic systems in the brain is a role in the control of water intake, and that these systems participate in an important way in drinking in response to angiotensin.
Abstract: 1. Intracranial or subcutaneous doses of atropine or atropine methyl nitrate that were fully effective at preventing drinking in response to intracranial carbachol did not block angiotensin-induced drinking. 2. The nicotinic antagonist dihydro-beta-erythroidine given intracranially affected neither angiotensin- nor carbachol-induced drinking. 3. The dopaminergic antagonists haloperidol and spiroperidol injected intracranially blocked angiotensin-induced drinking but did not affect carbachol-induced drinking. 4. Angiotensin- and carbachol-induced drinking were unaffected by alpha- or beta-adrenergic antagonists except at toxic doses. 5. Destruction of catecholaminergic neurones with 6-hydroxydopamine markedly reduced angiotensin-induced drinking, but had relatively little effect on carbachol-induced drinking. 6. Intracranial haloperidol reduced the amount of water drunk in response to overnight deprivation of water, but did not affect feeding in response to overnight starvation or to intracranial noradrenaline. 7. Drinking following overnight water deprivation was unaffected by intracranial alpha- or beta-adrenergic antagonists. 8. Preventing dopaminergic transmission with intracranial haloperidol decreased the water to food ratio of the rat's intake after overnight starvation, whereas increasing the dopamine levels with the combination of FLA-63 and L-DOPA increased the ratio. 9. Intraventricular dopamine in large amounts caused the water-replete rat to drink. 10. It is concluded that among the many functions of dopaminergic systems in the brain is a role in the control of water intake, and that these systems participate in an important way in drinking in response to angiotensin.
TL;DR: Mean plasma renin concentration was highest in the first trimester and fell significantly to the third trimester, although it remained above the normal nonpregnant range throughout pregnancy, and the plasma concentration of aldosterone was positively related to plasma sodium concentration.
Abstract: Plasma concentrations of renin, reninsubstrate, angiotensin II and aldosterone were measured in normal pregnant women at various stages of gestation and postpartum The mean circulating levels of renin-substrate, angiotensin II and aldosterone increased significantly from the first to the third trimester Mean plasma renin concentration was highest in the first trimester and fell significantly to the third trimester, although it remained above the normal nonpregnant range throughout pregnancy Unlike many other physiological and pathological situations in man, no significant relationship was found between concurrent plasma concentrations of renin and angiotensin II, renin and aldosterone or angiotensin II and aldosterone Plasma renin-substrate concentration did not correlate with plasma angiotensin II concentration, but it did have a positive correlation with plasma aldosterone concentration The plasma concentration of aldosterone was positively related to plasma sodium concentration, which was below th
TL;DR: It is suggested that glucocorticoid-induced hypertension may be initiated by alterations in vascular responsiveness to pressor agents and that elevated PRS levels may contribute to increase angiotensin formation.
TL;DR: In the conscious animal, prostaglandins appear to play only a minor role in the control of the renal circulation at rest, but are of greater importance in mediating the renal responses to reactive hyperemia and to vasoconstriction.
Abstract: Effects of indomethacin and meclofenamate, inhibitors of prostaglandin synthesis, were evaluated in the regulation of renal blood flow in conscious and anesthetized dogs and in tranquilized baboons, instrumented with arterial pressure catheters and renal blood flow probes. Indomethacin, 10 mg/kg, did not alter renal blood flow or resistance significantly in the conscious dog. In the anesthetized dog, however, indomethacin caused a reduction in renal blood flow (25 +/- 3% of control) and an elevation of renal vascular resistance (45 +/- 8% of control). Meclofenamate, 4 mg/kg, reduced renal flow (12 +/- 2%) and increased renal vascular resistance 15 +/- 4% in conscious dogs. In conscious dogs and tranquilized primates, indomethacin and meclofenamate reduced the reactive hyperemia in the renal bed after 15 s occlusion from a control of 36 +/- 5 ml to 6 +/- 2 ml, and after 45 s occlusion from a control of 98 +/- 9 ml to 17 +/- 5 ml. Methoxamine (10-50 mug/kg per min) and angiotensin II (0.03-0.12 mug/kg per min), infused in graded doses, induced significantly greater renal vasoconstriction in conscious dogs in the presence of indomethacin. Thus, in the conscious animal, prostaglandins appear to play only a minor role in the control of the renal circulation at rest, but are of greater importance in mediating the renal responses to reactive hyperemia and to vasoconstriction.
TL;DR: The intrarenal localization of 3 H-angiotensin II after intraaortic administration in anesthetized rats has been studied by autoradiography and the possibility of an action of angiotens in II at the level of the mesangial cells is discussed.
TL;DR: There is a close correlation of bradykinin levels with renin activity and angiotensin II, in both acute sodium loading and assumption of upright posture, suggesting that these two systems may be physiologically interrelated.
Abstract: The possibility that bradykinin, a potent vasodilator, might be a physiological antagonist of the renin-angiotensin system was investigated. 11 norman subjects, ranging in age from 21 to 33 yr were studied. Seven of the subjects were given a 10 meq sodium, 100 meq potassium, 2500 ml isocaloric diet. After metabolic balance was achieved, they were infused with either 1 liter of 5 per cent glucose over 2 h or 2 liters of 0.9 per cent saline over 4 h. During the infusions, plasma renin activity (PRA), angiotensin II (A II), prekallikrein, bradykinin, and aldosterone levels were frequently determined. Plasma prekallikrein and kallikrein inhibitor did not change during the infusion of either glucose or saline. In subjects receiving saline, plasma bradykinin fell from 3.9 plus or minus 1.5 (SEM) ng/ml at 0 min to 0.93 plus or minus 0.2 at 30 min and 0.95 plus or minus 0.3 at 120 min. These changes paralleled the decrease in PRA over the same period (7.9 plus or minus 1.3 ng/ml/h to 5.6 plus or minus 0.8 at 30 min and 3.5 plus or minus 0.7 at 120 min). Similarly, A II fell from 113 plus or minus 12 pg/ml to 62 plus or minus 10 and 48 plus or minus 5, respectively, at 30 and 120 min. In contrast, the control group infused with glucose showed no change in bradykinin, A II, or PRA. Another four subjects were given a constant 200 meq sodium/100 meq potassium isocaloric diet. After metabolic balance was achieved, they were kept supine and fasting overnight. At 9 a.m. they assumed an upright position and began walking a fixed distance (200 ft) at a normal rate (3-4 ft/s). Plasma prekallikrein and kallikrein inhibitor did not change during the posture study. The plasma bradykinin rose from a base line of 0.54 plus or minus 0.01 (SEM) ng/ml to 0.96 plus or minus 0.13 at 20 min. 0.77 plus or minus 0.18 at 60 min, and 0.96 plus or minus 0.07 at 120 min. These changes parallel the increase in PRA over the same period (1.65 plus or minus 3.3 ng/ml/h to 3.6 plus or minus 0.85 at 20 min, 5.3 plus or minus 0.9 at 60 min, and 5.35 plus or minus 0.55 at 120 min). Likewise, the A II rose from 32.5 plus or minus 1.82 pg/ml to 50.8 plus or minus 3.6 at 20 min, 54.3 plus or minus 3.2 at 60 min, and 61.3 plus or minus 5.9 at 120 min. Thus, in sodium-depleted individuals, saline infusion produces a rapid fall of plasma bradykinin at a rate similar to that observed for a II and PRA. Conversely, in sodium-loaded individuals, assumption of upright posture leads to a parallel rise in A II, TPRA, and bradykinin. These studies indicate that there is a close correlation of bradykinin levels with renin activity and angiotensin II, in both acute sodium loading and assumption of upright posture, suggesting that these two systems may be physiologically interrelated.
TL;DR: Data provide strong evidence that the renin-angiotensin system is responsible for the initiation of renov vascular hypertension in the one-kidney Goldblatt dog, but that other factors become increasingly important in chronic renovascular hypertension.
Abstract: Renal artery constriction in the unilaterally nephrectomized, trained dog, with maintained renal arterial hypotension, produces a prompt increase in systemic renin activity and blood pressure. The hypertension normally induced by renal artery stenosis is prevented by prior treatment with the nonapeptide Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro (SQ 20, 881), which blocks conversion of angiotensin I to angiotensin II. Constant intravenous infusion of the inhibitor over several days of renal artery constriction prevents the development of chronic renovascular hypertension. Furthermore, a single injection of the nonapeptide restores blood pressure to normal in the early phase of renovascular hypertension, but becomes progressively less effective as salt and water retention occurs in the chronic stage when plasma renin activity returns to control levels. These data provide strong evidence that the renin-angiotensin system is responsible for the initiation of renovascular hypertension in the one-kidney Goldblatt dog, but that other factors become increasingly important in chronic renovascular hypertension.
TL;DR: The data suggest that the renin-angiotensin-aldosterone system may play a role in blood pressure regulation during cardiopulmonary bypass and may result in the excessive urinary excretion of potassium and decrease in plasma potassium levels.
Abstract: Ten consecutive adult patients undergoing elective cardiac surgery with extracorporeal circulation were anesthetized using morphine (1-3 mg/kg) and nitrous oxide. Pre-bypass plasma renin activity showed a 3.5-fold elevation (P smaller than 0.001) over baseline values. This correlated with maximal blood pressure elevation. Plasma renin activity remained elevated during bypass. High baseline aldosterone levels increased 3.4-fold (P smaller than 0.001) after 15 minutes on bypass and 4.0-fold by the end of bypass. Plasma potassium decreased from 3.9 mEq/1 before bypass to 3.2 mEq/1 (P smaller 0.0001) during bypass, and the fractional urinary excretion of potassium was 32 per cent before bypass with a mean of 34.4 per cent during bypass. Urinary output remained high during bypass despite a progressive decrease in glomerular filtration rate. Catecholamine levels showed no significant change. The data suggest that the renin-angiotensin-aldosterone system may play a role in blood pressure regulation during cardiopulmonary bypass and may result in the excessive urinary excretion of potassium and decrease in plasma potassium levels.
TL;DR: It is suggested that the utero‐placental complex may be the source of the elevated AII levels and that suppressed levels of renin concentration and activity may result from elevated angiotensin levels.
TL;DR: Evidence is provided that aldosterone production by zona glomerulosa cells is influenced by changes in angiotensin II levels within the normal plasma range, and changes in the potassium concentration of cell incubation media accompany changes in steroidogenesis.
Abstract: The production of aldosterone by isolated canine zona glomenilosa cells was measured after the incubation of cell suspensions with angiotensin II and ACTH, and during changes in extracellular potassium concentration. Adrenal cell suspensions were prepared by collagenase digestion and physical dispersion of the capsular layer of the dog adrenal cortex, and aldosterone production was determined by direct radioimmunoassay of cell incubation media. The isolated dog adrenal cells were highly responsive to angiotensin II, with aldosterone production significantly stimulated by concentrations of the octapeptide as low as 10-11M. Thus, the steroidogenic response of zona glomenilosa cells was consistently observed at peptide concentrations within the physiological range of angiotensin II in dog plasma, i.e., 2.0–5.0 × 5.0 × 10-11M. The maximum aldosterone response of 3–8 times the basal level of steroid production was induced by 3 × 10-10M angiotensin II, and a decrease in aldosterone production occurred at peptid...
TL;DR: Results indicate that prostaglandins synthetized in skeletal muscle microcirculation in situ mediate, in part, vasodilator responses to bradykinin and modulate vasoconstrictor responses to angiotensin and norepinephrine, and support the hypothesis that prostglandins are local regulators of microvascular responsiveness.
Abstract: Recent reports have indicated that vascular responsiveness can be altered by exogenously administered or endogenously released prostaglandins. Furthermore, in certain tissues inhibitors of prostaglandin synthesis have been shown to limit the increase in blood flow in response to bradykinin and to enhance the reduction in blood flow in response to angiotensin and norepinephrine. These findings suggest an important local circulatory role for prostaglandins. We attempted to implicate further prostaglandins in local blood flow regulation by examining the effects of indomethacin (IND) and 5,8,11,14-eicosatetraynoic acid (ETA), inhibitors of prostaglandin synthesis, on microvascular arteriolar responses to bradykinin, prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), histamine, norepinephrine, and angiotensin. Male Wistar rats were anesthetized with sodium pentobarbital, and their cremaster muscle was exteriorized and prepared for in vivo microscopic observation of microvessels. Changes in arteriolar luminal diameters in response to topical administration of vasoactive agents were quantified with an image-shearing measuring eyepiece in conjunction with a television microscope and recorder. Local administration of IND or ETA significantly reduced the arteriolar dilation elicited by bradykinin, whereas the responses to PGE1 and PGE2 remained unaltered. Responses to histamine, although somewhat reduced, were not significantly different from control. Vasoconstrictor responses of arterioles elicited by norepinephrine and angiotensin were potentiated by IND or ETA administration. These results indicate that prostaglandins synthetized in skeletal muscle microcirculation in situ (1) mediate, in part, vasodilator responses to bradykinin and (2) modulate vasoconstrictor responses to angiotensin and norepinephrine. Thus, these findings support the hypothesis that prostaglandins are local regulators of microvascular responsiveness.