Showing papers on "Angiotensin II published in 1969"
TL;DR: Renin activity increased with Na restriction, was significantly higher on upright activity during both normal and restricted Na intake, and was most markedly elevated following the diuretic.
Abstract: A radioimmunoassay for angiotensin I and its application to the determination of renin activity is described. The assay employs antibodies raised to copolymers of angiotensin I and succinylated poly-l-lysine. Angiotensin labeled with 125I and purified by high voltage paper electrophoresis is employed as a tracer. Incubation is carried out in plasma in the presence of 3 metal binding reagents which serve to inhibit effectively proteolytic attack on angiotensin I. Immunoassay of generated angiotensin I is carried out directly on plasma diluted 1:20. Fifteen normal volunteers were studied on a metabolic ward at 2 levels of Na intake, during recumbency and upright posture, and following the administration of furosemide. Renin activity increased with Na restriction, was significantly higher on upright activity during both normal and restricted Na intake, and was most markedly elevated following the diuretic. Renin values obtained by immunoassay of angiotensin I correspond closely to those observed by ...
2,348 citations
TL;DR: Intravenous infusion of angiotensin causes rats which are in water balance to drink water and this results in Rats in Water balance in 1.1.
Abstract: 1. Intravenous infusion of angiotensin causes rats which are in water balance to drink water.2. The mean amount of angiotensin needed to initiate drinking was 29.1 +/- 4.6 mug/kg (S.E. of mean) in twenty normal rats, and 15.7 +/- 2.1 mug/kg in thirty-four nephrectomized rats.3. The nephrectomized rat is therefore more sensitive to this action of angiotensin than the rat with intact kidneys.4. The rates of infusion (0.05-3.0 mug/kg(-1) min(-1)) which cause drinking are comparable to those used to produce other effects in rats.5. Angiotensin restores the drinking response of the nephrectomized rat subjected to caval ligation to a value similar to that obtained in the uninfused normal rat subjected to caval ligation.6. The effects of angiotensin and hypertonic saline on drinking are additive when both substances are administered to nephrectomized rats.7. These experiments provide further support for the view that the renin-angiotensin system is concerned in extracellular thirst.
292 citations
TL;DR: The removal of prostaglandins by the lung restricts their activities to the organs from which they are released and between their organ of origin and the site in the pulmonary circulation where they are inactivated.
Abstract: STIMULATION of the splenic nerves releases prostaglandins from the spleen to give concentrations of as much as 0.2 µg/ml. in splenic venous blood1. The release of prostaglandins might influence organs remote from the site of release, for prostaglandins can exert potent actions on smooth muscle2. The lung has recently been shown to determine the fate of many vasoactive substances; some are activated—conversion of angiotensin I to angiotensin II (ref. 3)—and some inactivated. The degree of inactivation seems to be specific for a given substance, ranging from almost complete (bradykinin4, 5-hydroxytryptamine5, prostaglandins E1 E2 and F2α (ref. 1)), to minor (noradrenaline6), to allowance of their free passage (adrenaline6 and angiotensin II (ref. 7)). The removal of prostaglandins by the lung restricts their activities to the organs from which they are released and between their organ of origin and the site in the pulmonary circulation where they are inactivated1. A prostaglandin which passed through the lungs after its release from an organ could be considered a circulating hormone, as long as it is not rapidly degraded in the blood. Ferreira and Vane1 reported that prostaglandins E1 E2 and F2α were stable in blood, though rapidly inactivated by the lung. Removal of prostaglandins A1 and A2 by the lung was not determined because the assay organs are insensitive to them. Vascular smooth muscle, however, unlike other smooth muscle, is reactive to low concentrations of prostaglandins A1 and A2 (refs. 8–10) and the renal vasculature is probably most sensitive to prostaglandins A1 and A2 (refs. 10 and 11). Because the renal vasculature is also sensitive to prostaglandins E1 and E2 (ref. 12), it has been used as an index of the fate of prostaglandins infused into the venous and arterial circulations.
226 citations
TL;DR: It is suggested that the cumulative effects of repeated ingestion of ethanol in intoxicating doses can produce diminished LV function before clinical evidence of cardiac abnormality, or heart disease not necessarily related to malnutrition.
Abstract: Since many patients with cardiomyopathy have a history of chronic ethanolism often associated with malnutrition, we have evaluated left ventricular (LV) function in alcoholics with fatty liver, who had no clinical evidence of cardiac or nutritional disease.
During an afterload test of LV function the pressor response to angiotensin evoked a threefold rise of enddiastolic pressure in the alcoholic group which was substantially greater than the 4 mm Hg rise in control subjects. The stroke volume and stroke work response in the noncardiac alcoholic was significantly less than in controls. Diminished LV function was corroborated in the noncardiac alcoholic at rest, using a contractility index.
To evaluate the dose-response relationship of ethanol in the production of cardiac malfunction, two groups of noncardiac alcoholic subjects were studied acutely at low and moderate dose levels. After 6 oz, ventricular function, myocardial blood flow, and metabolism were not significantly affected. After 12 oz, there was a progressive rise of end-diastolic pressure and decrease of stroke output at a mean blood alcohol level of 150 mg/100 ml, reverting toward control by 4 hr. The coronary effluent transiently evidenced leakage of cell constituents, despite an increase of coronary blood flow, suggesting a direct but reversible cardiac injury. Myocardial extraction of triglyceride was enhanced, whereas FFA uptake was reduced. A possible role of myocardial triglyceride accumulation in heart muscle was considered in pathogenesis.
Chronic ingestion of 16 oz of Scotch daily by an alcoholic subject while on a normal diet produced, after 12 wk, a progressive increase of heart rate and size, circulation time, and venous pressure, and a ventricular diastolic gallop. Normal values were restored within 7 wk after interrupting alcohol.
These several studies suggest that the cumulative effects of repeated ingestion of ethanol in intoxicating doses can produce diminished LV function before clinical evidence of cardiac abnormality, or heart disease not necessarily related to malnutrition.
218 citations
TL;DR: A separate radioimmunoassay for angiotensin I has been developed, based on a highly specific antibody which was raised in rabbits by the intra-lymph-node and intra-splenic injection of isoleu 5 angiotENSin I adsorbed on to finely divided carbon black.
197 citations
TL;DR: Aldose reductase is present in human and rabbit aortas and provides a mechanism whereby hyper-glycemia can alter the metabolism of the arterial wall.
Abstract: Aldose reductase is present in human and rabbit aortas and provides a mechanism whereby hyper-glycemia can alter the metabolism of the arterial wall Aortic sorbitol concentration is regulated by ambient glucose concentration and is increased by epinephrine, isoproterenol, dibutyryl-3',5'-adenosine monophosphate, ouabain, and angiotensin II
119 citations
Journal Article•
TL;DR: The results suggest that angiotensin receptors on sympathetic nerve endings have different structural requirements than do muscle receptors and that levels of the peptide close to normal circulating plasma levels have the ability to modulate NE inactivation by uptake processes.
Abstract: Isolated rabbit hearts were perfused for 2 hr with Krebs' solution at 37°C, pH 7.3 to 7.35 and flow rates of 8 to 12 ml/min. H3-norepinephrine (H3NE), 10 ng/ml, was added to the perfusate, and the hearts were perfused for 15 min. The amount of H3NE accumulated in the heart was determined in the right auricle and left ventricle by scintillation counting. Total myocardial NE was determined fluorometrically. Angiotensin II (02 ng/ml) and angiotensin amide (2.0, 0.2 and 0.05 ng/ml) inhibited the uptake of H3NE. Addition of blood to the perfusate decreased the amount of inhibition obtained with peptide administration. When significant inhibition of uptake occurred, there was a potentiation of the positive chronotropic response to NE. Angiotensin also inhibited the uptake of H3-metaraminol. Several analogs of angiotensin were studied in an attempt to determine thestructural requirements needed for uptake inhibition in the heart. In general, changes in positions 1 to 7 showed good correlation between inhibition of H3NE uptake and pressor activity. However, a similar correlation was not found with peptides substituted in position 8. These analogs had pressor activities ranging from 0.1 to 10% but produced marked inhibition of H3NE accumulation. These results suggest that angiotensin receptors on sympathetic nerve endings have different structural requirements than do muscle receptors and that levels of the peptide close to normal circulating plasma levels have the ability to modulate NE inactivation by uptake processes.
87 citations
83 citations
Journal Article•
79 citations
TL;DR: In the rat pretreated with sodium pentobarbital and chlorpromazine, none of the amino acids, amino acid mixtures, various di- and tripeptides, or biogenic amines exhibited a significant effect on pituitary-addrenal activity, however, prostaglandin E1 and E2, in contrast to F1α and F2α, stimulated pituitsary ACTH release in rats blocked with Sodium pentobarBital andchlorpromazine.
Abstract: The ACTH-releasing activity of some substances of low molecular weight was tested in several assay systems in the rat, in which attempts were made to block the nonspecific release of ACTH. The rate of corticosteroid production in vitro and corticosterone content of plasma were used as parameters of pituitary ACTH release. In the rat pretreated with sodium pentobarbital and chlorpromazine, none of the amino acids, amino acid mixtures, various di- and tripeptides, or biogenic amines exhibited a significant effect on pituitary-addrenal activity. However, prostaglandin E1 and E2, in contrast to F1α and F2α, stimulated pituitary ACTH release in rats blocked with sodium pentobarbital and chlorpromazine. Angiotensin II, arginine vasopressin, carbachol and a crude CRF from calf brain also activated the pituitary-adrenal system of similarly blocked rats. The corticotrophic effect of these “active agents” was further studied in rats pretreated with sodium pentobarbital, atropine and chlorpromazine; sodium pentobarb...
72 citations
TL;DR: The effect of stimulating and suppressive influences on plasma aldosterone in normal man and in patients with primary aldosteronism were studied using a sensitive double-isotope derivative assay for ald testosterone.
Abstract: The effect of stimulating and suppressive influences on plasma aldosterone in normal man and in patients with primary aldosteronism were studied using a sensitive double-isotope derivative assay for aldosterone.
In normal sitting subjects, values were 9.2±0.9 (SE) mμg/100 ml and in subjects supine for 1 hr plasma aldosterone was 5.2±0.4 (SE) mμg/100 ml. Adrenocorticotropic hormone (ACTH), 0.5 U/hr, produced a rise of 46.8±22 (SE) mμg which was similar to the 1-hr effect of an infusion of a synthetic ACTH (β1-24, Cortrosyn). Angiotensin II in pressor amounts also increased plasma aldosterone 21.5±2.9 (SE) without change in plasma cortisol, whereas a subpressor dose ([unk]) had minimal effect.
Fludrocortisone, 1.2 mg/day for 3 days, suppressed plasma aldosterone levels to 1.8±0.7 (SE) mμg/100 ml in five normal sitting subjects (P < 0.01); however, dexamethasone, 2 mg/day for 1-2 days, did not lower aldosterone concentration in plasma.
In six patients with primary aldosteronism, plasma aldosterone on a normal sodium diet was 39.1±4.4 (SE) which differed significantly from normal sitting or supine subjects (P < 0.001). In contrast to the normal subjects, neither a pressor infusion of angiotensin II for 1 hr, nor fludrocortisone, 1.2 mg/day for 3 days, impressively altered plasma aldosterone levels.
This approach appears to be useful for the study of the acute physiology and control mechanisms of aldosterone production in normal and hypertensive man.
TL;DR: The radioimmunoassay for angiotensin II which was previously described has been revised, improved and simplified and may be applied to measurement of renin activity, giving average values of 0.73±0.32 U/ml plasma in normal subjects.
Abstract: The radioimmunoassay for angiotensin II which we previously described has been revised, improved and simplified. Plasma angiotensin II concentration in normal subjects on unrestricted sodium intake averages 21±10 μμg/ml. The method may be applied to measurement of renin activity, giving average values of 0.73±0.32 U/ml plasma in normal subjects. Variation in sodium intake, activity and the administration of diuretics in normal subjects produce expected changes in both circulating angiotensin and renin activity. Anephric subjects show absent circulating angiotensin and very low but measurable renin activities.
TL;DR: A primary role for angiotensin in both forms of renal hypertension is suggested, with results suggesting that different mechanisms may be involved in the three types of hypertension studied.
Abstract: The role of angiotensin in three forms of experimental hypertension was assessed in rats. First, the acute blood pressure response to injected angiotensin amide and angiotensin acid was determined. Rats made hypertensive with deoxycorticosterone and saline showed exaggerated responses; rats made hypertensive by clipping one renal artery showed depressed responses; and rats made hypertensive by clipping one renal artery and contralateral nephrectomy showed normal responsivity to angiotensin amide but depressed responsivity to angiotensin acid. These findings suggested that different mechanisms may be involved in the three types of hypertension studied.
To assess the role of angiotensin in these hypertensive rats the blood pressure response, the presence of antibodies determined by radioimmune techniques, and the degree of refractoriness to injected angiotensin after immunization with angiotensin were studied. None of six rats made hypertensive by deoxycorticosterone and saline, and none of five mock immunized rats with renal hypertension of both types had a fall in blood pressure. By contrast, of the 20 rats with both types of renal hypertension in which antibody determinations were made, 11 had developed a significant antibody titer, of which seven showed a significant reduction in blood pressure at the time of antibody determination, and three of the remaining four had a significant blood pressure reduction earlier in their course. None of the nine renal hypertensive rats without demonstrable antibodies had a reduced blood pressure at the time of antibody determination, and only one had an earlier reduction in blood pressure. The renal hypertensive rats were all refractory to injected angiotensin after immunization.
These results suggest a primary role for angiotensin in both forms of renal hypertension.
TL;DR: The effect of val-aangiotensin-II-amide on tubular sodium and water reabsorption in the rat kidney was studied by micropuncture techniques.
Abstract: The effect of val-aangiotensin-II-amide on tubular sodium and water reabsorption in the rat kidney was studied by micropuncture techniques. An angiotensin infusion of 0.2–0.5 µg/min/kg caused a signif
TL;DR: Tissue peptidases are the enzymes chiefly responsible for the removal of angiotensin II in rat liver and kidney.
Abstract: Tissue peptidases are the enzymes chiefly responsible for the removal of angiotensin II in rat liver and kidney.
TL;DR: In vivo microscopy was utilized to evaluate the vasomotor action of prostaglandin E1 (PGE1) and prostaglandsin F2α (PGF2α) in the mesocecal and cremasteric muscle circulation of the rat.
Abstract: In vivo microscopy was utilized to evaluate the vasomotor action of prostaglandin E1 (PGE1) and prostaglandin F2α (PGF2α) in the mesocecal and cremasteric muscle circulation of the rat. Vessel dimensions were monitored by using a novel system consisting of microscope, image-splitting eyepiece, television camera, videoscreen, and a write-out apparatus giving exact minute to minute measurements of the microvessel lumen diameter. Intravenous administration of PGE1 decreased systemic blood pressure with a concomitant increase in diameter of the metarterioles of the cremaster muscle and a decrease in diameter of the metarterioles of the mesocecum; it effectively inhibited the constrictor effect of topically applied norepinephrine and epinephrine on the mesocecum metarterioles. Constrictor effects of topically applied angiotensin II were not altered. Intravenous PGF2α increased systemic blood pressure with a concomitant decrease in metarteriolar diameter in both the mesocecum and cremaster muscles. The vascular...
TL;DR: A specific radioimmunoassay for angiotensin II has shown that its normal concentration in arterial blood is 2·4±1·2 (S.D.) mμg./l00 ml.
Abstract: A specific radioimmunoassay for angiotensin II has shown that its normal concentration in arterial blood is 2·4±1·2 (S.D.) mμg./l00 ml.; the venous level is consistently below this value, being usually 50–75% of it. Definite rises in blood angiotensin II levels were found in some patients with hypertension, both essential and secondary to renal disease. Extremely low levels were observed in two anephric women, and in one patient with Conn's syndrome. This radioimmunoassay offers a valuable alternative to renin bioassay in evaluation of the role of the renal pressor system in clinical disorders associated with hypertension and aldosteronism.
TL;DR: Application of the systemic pressure response technic has proved to be easy and safe during cardiac catheterization in man, and it can now be used to study the fate of vasoactive drugs or hormones in the pulmonary circulation.
Abstract: The systemic pressure response technic was applied in 4 patients undergoing diagnostic catheterization. Injections were made alternately into the pulmonary artery and the ascending aorta and the systemic arterial pressor responses to each of these two routes of administration were compared. In 2 subjects, the pressor potency of angiotensin II given by way of the pulmonary artery was identical to that resulting from aortic injections, thus indicating the absence of pulmonary extraction of the octapeptide. In 2 other patients, angiotensin I was twice as potent by the pulmonary than by the aortic route; this could have resulted only from the marked conversion of the inactive decapeptide under the influence of pulmonary converting-enzyme activity. These data provide the clinical confirmation of previous animal observations pointing to the important role played by the lungs in the renin-angiotensin system. Application of the systemic pressure response technic has proved to be easy and safe during cardiac catheterization in man, and it can now be used to study the fate of vasoactive drugs or hormones in the pulmonary circulation.
TL;DR: It is suggested that the elevated renin activity of pregnancy is one of several aetiological factors in the development of toxaemia of pregnancy, and that those women with more striking elevation in early pregnancy are more prone to develop toxaemic later in pregnancy.
TL;DR: It may be that the small variations in endogenous plasma renin activity that have been observed in primary aldosteronism may be capable of evoking large changes in ald testosterone secretion in patients with aldosterone-producing adenomas.
Abstract: Angiotensin infusion evokes marked increases in aldosterone secretion in primary aldosteronism and little change in secondary aldosteronism. The low plasma renin activity of primary aldosteronism and the elevated plasma renin activity of secondary aldosteronism are thought to account for this differential response. The effect of angiotensin on aldosterone and 18-hydroxycorticosterone secretion was studied during adrenal vein catheterization in seven patients with primary aldosteronism (whose plasma renin activity had been elevated following spironolactone therapy), one hypertensive patient with normal plasma renin activity and normal aldosterone secretion, two patients with secondary aldosteronism who had elevated plasma renin activity, and one anephric patient whose plasma renin activity was 0. Adrenal venous aldosterone and 18-hydroxycorticosterone were measured before and after a ten min sub-pressor angiotensin infusion.
The cells of the aldosterone-producing adenoma (APA) respond to small increases in plasma angiotensin with large increases in secretion of aldosterone and 18-hydroxycorticosterone. The dose of angiotensin capable of evoking this response from the aldosterone-producing adenoma produces little or no change in the secretion of the steroids from nontumorous glands. The augmentation of aldosterone secretion, induced by angiotensin, in primary aldosteronism is due solely to increased secretion by the adenoma and not by the contralateral zona glomerulosa. The increased sensitivity of the aldosterone-producing adenoma is characteristic of the tumor. This response is independent of fluctuations in endogenous plasma renin activity. This sensitivity is not blunted by high plasma renin activity, nor is it a function of tumor mass for the effect is observed in aldosterone-producing adenomas regardless of size. ACTH injection after angiotensin infusion resulted in a marked increase in aldosterone concentration in the effluent from the nontumorous adrenal, but was not capable of producing further increases in aldosterone concentration in the effluent from the APA. In view of this exquisite sensitivity to infused angiotensin, it may be that the small variations in endogenous plasma renin activity that have been observed in primary aldosteronism may be capable of evoking large changes in aldosterone secretion in patients with aldosterone-producing adenomas.
TL;DR: It was considered that vertebral injection of angiotensin II in humans caused a rise in blood pressure partly by increasing the sympathetic nerve activity.
Abstract: Responses to vertebral and aortic injection of synthetized angiotensin II of the systemic arterial pressure and heart rate were examined in humans and the following results were obtained:Angiotensin II injections in the dosages from 0.016 to 0.06μg./Kg. caused the following effects.1) Vertebral injection produced a higher rise in the systemic arterial pressure than that produced by aortic injection of the same dose.2) Heart rate was increased by vertebral injection of a small dose, but was decreased by aortic injection.From these data, it was considered that vertebral injection of angiotensin II in humans caused a rise in blood pressure partly by increasing the sympathetic nerve activity.
Journal Article•
TL;DR: Renin activity can be determined by measuring the quantity of angiotensin generated during incubation of plasma under standard conditions, and A I rather than A II is the product of the renin activity in the Boucher procedure, which can be measured adequately with a radioimmunoassay for A I.
TL;DR: A radioimmunoassay capable of detecting 30 pg of angiotensin II has been developed, and extended for use in the estimation of ang Elliotensin in circulating plasma.
Abstract: Specific antibody against free angiotensin II has been raised in high titre by immunizing rabbits with angiotensin II amide ('Hypertensin', Ciba) adsorbed on to micro-particles of carbon. The material was injected either parenterally or directly into lymph nodes and spleen. A radioimmunoassay capable of detecting 30 pg of angiotensin II has been developed, and extended for use in the estimation of angiotensin in circulating plasma. The validity of this application of the assay has been established in experiments where plasma levels of this hormone were studied in relation to the intravenous infusion of Val$^{5}$-angiotensin II amide in humans. Present results of the investigation of the circulating plasma angiotensin II levels in various physiological and pathological states are presented.
TL;DR: The paper describes details of a radioimmunoassay for angiotensin-II modified to replace the bioassay of angiotENSin as used for the estimation of renin in blood, and high titre antibodies with association constants were obtained in rabbits.
Abstract: The paper describes details of a radioimmunoassay for angiotensin-II modified to replace the bioassay of angiotensin as used for the estimation of renin in blood. High titre antibodies with association constants of 7 X 109 to 3 X 1010 l/mole were obtained in rabbits, using carbodiimide condensation of angiotensin-II to γ-globulin. The radioimmunoassay for angiotensin-II is adapted to be performed at the relatively high concentration of plasma found in the plasma pool used for renin assay. Thus, this assay may be carried out directly on the solutions used for renin assay. By adjustment of the method to a high precision, the angiotensin-II formed by the enzyme reactions can be measured to an accuracy of ± 4 % (S. D.).
TL;DR: The present results show that in the dog a high-sodium diet can eliminate the steroidogenic action of angiotensin II, which is thus dissociated from the pressor action which remains.
Abstract: The pressor octapeptide, angiotensin II, can stimulate the production of aldosterone by the adrenal cortex. The present results show that in the dog a high-sodium diet can eliminate the steroidogenic action of angiotensin II, which is thus dissociated from the pressor action which remains.
Angiotensin II was infused intravenously for 48 hours into conscious, undisturbed hypophysectomized dogs that were receiving each day either 60 or 200 mEq of dietary sodium. Blood pressure and secretion of aldosterone, corticosterone, and cortisol were measured (1) throughout the infusion in some dogs, and (2) at the end of the infusion in all dogs. In those dogs receiving 60 mEq of sodium, angiotensin II elevated the blood pressure and produced sustained increases of secretion of aldosterone, corticosterone, and cortisol. In those dogs receiving 200 mEq of sodium, angiotensin II, while retaining its pressor activity, had no effect on the production of aldosterone, corticosterone, or cortisol after 24 hours. Thus, if angiotensin II can produce hypertension clinically, there need not be secondary aldosteronism as well.
TL;DR: Evidence is provided for the involvement of the carotid sinus-body structures and the central nervous system as additional loci for the cardiovascular effects of PGE1.
TL;DR: The method, using 300 μl plasma, gives simultaneously renin concentration, renin activity, and renin-substrate concentration without chromatographic steps.
Abstract: Renin is measured by the rate of renin-substrate consumption with time. Renin-substrate is measured by conversion to angiotensin-II by excess of renin and converting enzyme. Characteristics: precisely determined angiotensinogen conc. during reaction, controlled converting enzyme activity, and eliminated influence of angiotensinases. The method, using 300 μl plasma, gives simultaneously renin concentration, renin activity, and renin-substrate concentration without chromatographic steps. Detection limit is 22 times lower than normal mean. Precision ± 6 %.