Showing papers on "Angiotensin II published in 1971"
TL;DR: A sensitive, fixed-time, spectrophotometric assay for angiotensin-converting enzyme measures the rate of production of hippuric acid from hippuryl-L -histidyl- L -leucine (HHL).
2,493 citations
TL;DR: High specific activities of converting enzyme were found in lung and in segments of the digestive tract, but the highest activities were in testis and epididymis, associated with tubular fluids, but not in sperm cells.
413 citations
TL;DR: An enzyme with the characteristics of classical renin was isolated from brain extracts of nephrectomized dogs and a remarkable correlation was found between angiotensin and norepinphrine concentrations in different portions of the encephalon of the dog.
Abstract: An enzyme with the characteristics of classical renin was isolated from brain extracts of nephrectomized dogs. This enzyme is thermolabile, nondialyzable, and forms a vasoconstrictive material when incubated with renin plasma substrate at pH 7. A short lasting pressor activity was also found in brain extracts of dogs and rats. This activity was due to a substance identified by chemical and pharmacological tests as angiotensin. Countercurrent distribution of brain extracts of rats showed that 38% of the pressor activity corresponded to angiotensin II and the remainder to angiotensin I. A remarkable correlation was found between angiotensin and norepinphrine concentrations in different portions of the encephalon of the dog.
345 citations
TL;DR: Data indicate that angiotensin II is in fact critically involved in the pathogenesis of the form of renal hypertension in which one renal artery is clamped and the contralateral kidney is left in place, but that it probably plays no significant role in the maintenance of experimental renal hypertension, in which the opposite kidney has been removed.
Abstract: Antibody to angiotensin 11, or a specific peptide competitive inhibitor of angiolensin II, was used to investigate the role of the renin-angiotensin system in two types of renal hypertension in rats The data indicate that angiotensin II is in fact critically involved in the pathogenesis of the form of renal hypertension in which one renal artery is clamped and the contralateral kidney is left in place, but that it probably plays no significant role in the maintenance of experimental renal hypertension in which the opposite kidney has been removed
334 citations
TL;DR: The data indicate that, under certain experimental conditions, the blood pressure of rats during the acute phase of unilateral renal hypertension is maintained hy the endogenous angiotensin II, which was previously demonstrated to he present in the plasma in supernormal concentrations.
Abstract: Experiments with rabbit aortic strips and pithed rats indicated that 1-Sar-8-Ala-angiotensin II (Sar-Arg-Val-Tyr-Val-His-Pro-Ala) is a specific competitive antagonist of the vascular action of angiotensin II. Norepinephrine-induced hypertension was not affected by infusions of 1-Sar-8--Ala-angiotensin II which evoked a dose-related reduction of angiotensin II-induced hypertension in conscious rats. Infusions of 1-Sar-8-Ala-angiotensin II that caused a dose-related reduction of the blood pressure of conscious rats in the acute phase of unilateral renal hypertension were ineffective during the chronic phase of such hypertension. Infusions of 1-Sar-8-Ala-angiotensin II lasting 1 hour did not reduce the blood pressure of normotensive, spontaneously hypertensive, or metacorticoid hypertensive conscious rats. These data indicate that, under certain experimental conditions, the blood pressure of rats during the acute phase of unilateral renal hypertension is maintained hy the endogenous angiotensin II previously demonstrated to he present in the plasma in supernormal concentrations. The blood pressure of normotensive, spontaneously hypertensive, metacorticoid hypertensive, and chronic unilateral renal hypertensive rats previously shown to have normal plasma levels of renin and angiotensin II appeared to be independent of the pres.sor action of endogenous angiotensin II. This is additional direct evidence implicating the pressor action of angiotensin II in the etiology of renal hypertension.
315 citations
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TL;DR: A renin-angiotensin system, independent of that of the kidney, is present in brains of nephrectomized dogs, and levels of renin activity remain as high as in control dogs.
Abstract: GANTEN, DETLEV, ANA MARQUIZ-JULIO, PIERRE GRANGER, KARL HAYDUK, KLAUS PETER KARSWNKY,ROGER BOUCWER, AND JACQUES GENEST. Renz'n ilz dog brain. Am. J. Physiol. 221(6): 17331737. 1971 .-Brain tissue of dogs contains high renin activity. After peritoneal dialysis in nephrectomized dogs for up to 12 days, levels of renin activity remain as high as in control dogs. Kenin substrate and angiotensin are present in brain after nephrectomy. Plasma renin and substrate do not pass the blood-cerebrospinal Auid barrier. Thus a renin-angiotensin system, independent of that of the kidney, is present in brains of nephrectomized dogs.
299 citations
Journal Article•
TL;DR: A dipeptide hydrolase was purified 200-fold from hog plasma and concentrated from homogenates of lung and kidney, but the highest specific activity was found in a particulate fraction of the kidney.
Abstract: A dipeptide hydrolase was purified 200-fold from hog plasma and concentrated from homogenates of lung and kidney. Guinea-pig plasma is a very rich native source of the enzyme, but the highest specific activity was found in a particulate fraction of the kidney. The enzyme has a dual function: it converts angiotensin I into angiotensin II, and it inactivates bradykinin by cleaving off the C-terminal dipeptides His-Leu or Phe-Arg, respectively. Thus, kininase II is also an angiotensin I converting enzyme. In addition, this enzyme released C-terminal dipeptides from five other shorter peptide substrates. Three of them were used as substrates in ultraviolet spectrophotometric experiments. The activity of dipeptide hydrolase was inhibited by ethylenediamine tetraacetic acid, and several divalent metal ions restored its activity. It was also inhibited by the dipeptide split products of the reactions, by a pentapeptide, by insulin and by the B chain of insulin.
279 citations
TL;DR: A radioimmunoassay method for the measurement of angiotensin II in human plasma is described and the hormone is extracted quickly by Dowex (H+) particles.
Abstract: . A radioimmunoassay method for the measurement of angiotensin II in human plasma is described. The hormone is extracted quickly by Dowex (H+) particles. Angiotensinase and converting enzyme are inhibited by a mixture of EDTA and o-phenanthroline. Blood samples can be processed at room temperature. Recoveries from blood were 83%± 11 (SD), n=44. Replicates within one assay varied about their mean with a standard deviation of ± 10%, n=16. The smallest concentration detectable, using 10 ml plasma samples, was 2 pg/ml plasma. Peripheral venous plasma concentrations in 33 normal adults ranged from 5 to 35 pg/ml. Plasma angiotensin II concentrations in some physiological and clinical conditions are reported.
273 citations
TL;DR: The accuracy of the isolated adrenal cell method for assay of ACTH is excellent and the cells are highly selective; they do not respond to relatively large quantities of insulin, glucagon, oxytocin, vasopressin or angiotensin II.
Abstract: Rat adrenal tissue is dispersed with a combination of tryptic digestion and mechanical agitation. Production of corticosterone by the isolated cells in response to a given quantity of ACTH is increased when the calcium concentration of the incubation medium is increased to 3 times that of KRB. Production of corticosterone is enhanced when BSA is added to the medium; production is greater at 0.5% than at 2.0 or 3.0% BSA. Minimum effective dose is 0.1 μU (1.0 pg) of ACTH. The accuracy of the isolated adrenal cell method for assay of ACTH is excellent; λ = 0.01–0.06 compared with λ =0.15–0.25 for other currently employed bioassay methods. In addition, the cells are highly selective; they do not respond to relatively large quantities (107 pg) of insulin, glucagon, oxytocin, vasopressin or angiotensin II. At 107 pg, α-MSH exhibits a weak action corresponding to that exhibited by 10 pg of ACTH. (Endocrinology 88: 1063, 1971)
250 citations
TL;DR: The selective cellular localization of angiotensin II suggests that this vasoactive agent or some of its metabolic fragments may have specific effects on nuclear function.
Abstract: Five to ten nanograms of labeled angiotensin II rapidly injected in the left ventricle of adult rats was found to induce significant ultrastructural endothelial changes, resulting in net increases in number and size of pinocytotic vesicles as well as widening of intercellular spaces. This effect was followed by preferential localization of the compound in the nuclear zone of vascular and cardiac muscle cells. The selective cellular localization of angiotensin II suggests that this vasoactive agent or some of its metabolic fragments may have specific effects on nuclear function.
243 citations
TL;DR: In the present experiments the dipsogenic action of a number of other substances including substances related to angiotensin was tested, finding that these substances did not cause the rat to drink water.
Abstract: 1. Recently it has been shown that injection of angiotensin II into the anterior diencephalon causes the rat to drink water. In the present experiments the dipsogenic action of a number of other substances including substances related to angiotensin was tested.
2. Injection of 0·001 Goldblatt u. renin into the angiotensin-sensitive region causes the water-replete rat to drink. Drinking is slower in onset and continues for longer than after injection of angiotensin II.
3. Synthetic tetradecapeptide renin substrate and angiotensin I were as effective as angiotensin II at causing water-replete rats to drink.
4. β-aspartic acid1-valine5-angiotensin II was also fully effective; but the D-arginine substituted octapeptide was much less effective.
5. The (2–8) heptapeptide retained about 50% of the dipsogenic activity of the octapeptide, whereas the absence of phenylalanine at the other end of the peptide chain in the (1–7) heptapeptide results in an inactive compound.
6. The (3–8) hexapeptide and the (4–8) pentapeptide, both of which have phenylalanine at the end of the chain, and the (1–4) and (5–8) tetrapeptide fragments of angiotensin II showed only a slight action on intake of water.
7. Kallikrein, bradykinin, adenosine-3′5-cyclic phosphate, vasopressin and oxytocin caused no drinking when injected into the angiotensin-sensitive region.
8. It is concluded that the requirements for the dipsogenic activity of angiotensin are the same as those for its other biological actions with the qualification that the precursor peptides are also active, presumably because they give rise to angiotensin II locally.
TL;DR: It is suggested that angiotensin is able to facilitate the release of the sympathetic transmitter and that this is the basis for its action in potentiating the responses to sympathetic stimulation.
Abstract: 1. The effects of angiotensin on the contractility of the transmurally stimulated rabbit portal vein and coeliac artery have been studied in conjunction with its effects on the release and uptake of (±)-3H-noradrenaline.
2. Angiotensin contracted both vein and artery; these responses were enhanced by veratrine and reduced by tetradotoxin. At low (non-contractile) concentrations of angiotensin, contractions elicited by electrical stimulation (0·5-4 Hz) had a quicker onset and reached a higher maximal tension than control responses. Higher concentrations of angiotensin increased the degree of potentiation. Contractions to noradrenaline were not enhanced by angiotensin.
3. Pretreatment of the coeliac artery, portal vein and perfused rat heart with angiotensin did not reduce the subsequent uptake of labelled noradrenaline in the presence of angiotensin. Simultaneous treatment with angiotensin and 3H-noradrenaline caused a small, apparent inhibition of uptake into the portal vein.
4. When the portal vein was incubated with 3H-noradrenaline there was a marked accumulation of label within the tissue; over 90% of the radioactivity retained in the tissue was identified as intact noradrenaline. When the vein, or artery, was superfused with amine-free Krebs there was a steady basal release of label; the greater proportion of this label was identified as deaminated metabolites. Electrcal stimulation evoked a frequency dependent release of 3H above basal levels. The greater proportion of this increased efflux was due to the release of intact 3H-noradrenaline, with smaller increases in the amount of O-methylated and deaminated metabolites.
5. Angiotensin increased the efflux of labelled noradrenaline + normetanephrine, or of total 3H, during transmural stimulation (0·5-4 Hz) in both the vein and artery, but did not increase the efflux of deaminated products during electrical stimulation. The output of labelled noradrenaline + normetanephrine was usually doubled in the presence of angiotensin (200-500 ng/ml) during electrical stimulation of the portal vein.
6. Cocaine (4 μg/ml) potentiated responses to noradrenaline and transmural stimulation, and doubled the output of 3H or labelled noradrenaline + nor-metanephrine during electrical stimulation. Cocaine did not alter the potentiating effects of angiotensin.
7. Angiotensin elicited transitory increases in the basal efflux of 3H from both the portal vein and coeliac artery. However, this did not account for the marked increase in efflux seen during electrical stimulation. Vasopressin did not potentiate responses to transmural stimulation or significantly influence the efflux of 3H from the vein or artery.
8. Noradrenaline and 5-hydroxytryptamine, but not acetylcholine, markedly increased the efflux of 3H from the portal vein. This increase in efflux of label is believed to result from an exchange of exogenous noradrenaline and 5-hydroxytryptamine with labelled tissue stores of noradrenaline.
9. It is suggested that angiotensin is able to facilitate the release of the sympathetic transmitter and that this is the basis for its action in potentiating the responses to sympathetic stimulation. It is also suggested that the nor-adrenaline releasing action of angiotensin (by excitation of sympathetic nerve endings) has led to confusion in previous investigations of the effects of angiotensin on noradrenaline uptake.
TL;DR: The effect of local adrenal arterial infusion of the heptapeptide (2-8) and hexapeptides (3-3) fragments of angiotensin 11 on a aldosterone secretion was examined.
Abstract: The effect of local adrenal arterial infusion of the heptapeptide (2-8) and hexapeptide (3-8) fragments of angiotensin 11 on a aldosterone secretion was examined. The heptapeptide (2-8) resembled the octapeptide in activity and stimulated aldosterone whereas the hexapeptide (3-8) had no effect.
TL;DR: The data presented are consistent with the conclusion that 1-Asn-8-Ala-angiotensin II is a specific competitive antagonist of the vascular action of angiotens in II both in vitro and in vivo.
Abstract: The effect of 1-Asn-8-Ala-angiotensin II (Asn-Arg-Val-Tyr-Val-His-Pro-Ala) on the vascular action of angiotensin II was studied with rabbit aortic strips, pithed rats, and conscious rats. Dose-response (contraction) curves for angiotensin II on rabbit aortic strips shifted progressively to the right with increasing bath concentrations of 1-Asn-8-Ala-angiotensin II. The pA2 value (an indication of the relative affinity of a competitive antagonist for an agonist's receptor site) was 6.84 ± 0.03. Dose-response curves for norepinephtine, serotonin, and histamine were relatively unaffected. No pA3 values could be obtained with these agonists in the concentration range tested. Partial dose-response (pressor) curves for angiotensin II in pithed rats shifted to the right during infusions of 1-Asn-8-Ala-angiotensin II at 20 and 60 µg/kg min-1 Partial dose-response curves for vasopressin, phenylephririe, and tyramine were unaffected. Infusions of 1-Asn-8-Ala-angiotensin II counteracted the pressor effect of angiote...
TL;DR: The results may have important clinical significance, since they suggest that measures likely to increase renin and angiotensin (such as diuretic administration) should be avoided in acute (and certain examples of chronic) renal failure.
TL;DR: It is reported that angiotensin II increases the discharge rate of these and other neurones in the supraoptic nucleus by applying angiotENSin II directly to individual supra optic neurosecretory cells.
Abstract: ANGIOTENSIN II, a circulating peptide which regulates electrolyte balance by controlling the adrenal release of aldosterone, may also act on the central nervous system. The reported central effects include elevations of blood pressure1–6, drinking behaviour7–11, adrenocorticotrophic hormone release12,13 and antidiuretic hormone (ADH) release5,14,15. The evidence for ADH release from the supraoptico-neurohypophysial system is based on studies involving the parenteral and intraventricular administration of angiotensin II. These routes of administration make an exact localization of the releasing action impossible and therefore we have attempted to locate the site by applying angiotensin II directly to individual supraoptic neurosecretory cells. We now report that angiotensin II increases the discharge rate of these and other neurones in the supraoptic nucleus.
TL;DR: Levels in lymph suggested that angiotensin II is partially removed from arterial plasma by hydrolysis during transit through the kidney, and it was concluded that angiotsin II levels in lymph reflected the concentration of angiotensor I in renal tissue.
Abstract: Angiotensin II was determined by radioimmunoassay in systemic arterial, pulmonary arterial, and renal venous plasma and in renal hilar lymph in dogs. Levels of the peptide were determined prior to and during progressive graded hemorrhage or reduction in renal perfusion pressure. Levels of angiotensin II in plasma consistently rose during transit through the lung indicating pulmonary conversion of angiotensin I to angiotensin II. On the other hand, angiotensin II in the renal vein plasma was less than that in arterial plasma indicating renal extraction of the peptide from plasma. When renal hilar lymph was sampled under similar conditions, angiotensin II in lymph was consistently higher than that in arterial or renal venous plasma. Furthermore, in some experiments angiotensin II in lymph increased at a time when the concentration in plasma was undetectable. No evidence was found to indicate that angiotensin II in plasma entered renal lymph. It was concluded that angiotensin II levels in lymph reflected the concentration of angiotensin II in renal tissue. The data further suggested that angiotensin II is partially removed from arterial plasma by hydrolysis during transit through the kidney.
TL;DR: Data indicate that angiotensin elicits a direct positive inotropic effect which is independent of intact adrenergic nerves or endogenous catecholamine stores.
Abstract: DEMPSEY, PETER J., ZENA T. MCCALLUM, KENNETH M. KENT, AND THEODORE COOPER. Direct myocardial efects of angiotensin 11. Am. J. Physiol. 220(Z) : 477-481. 1971.-There still remains speculation concerning the existence of a direct effect of angiotensin II on ventricular myocardium. Evaluation has been complicated by the sensitivity of the peripheral circulation in intact preparations, reflex mechanisms, and disagreement concerning the role of ganglia and endogenous catecholamine stores. TWO series of experiments were designed that used hearts from normal cats and from cats that had undergone extrinsic cardiac denervation to deplete catecholamines. In the first series, 19 isolated perfused hearts were studied in a Langendorff apparatus. In the second series, tension and transmembrane action potentials were recorded from 20 right ventricular papillary muscles. In normal and denervated ventricular myocardium angiotensin (lo--lo g/ml-lo-” g/ml) elicited a positive inotropic effect characterized by an increased maximum rate of tension rise and rate of relaxation, but not in a shortened time to peak tension. A change in the form of phase 2 of the action potential was noted. These data indicate that angiotensin elicits a direct positive inotropic effect which is independent of intact adrenergic nerves or endogenous catecholamine stores.
TL;DR: The significance of the renin-angiotensin system as a hormonal basis for thirst is extended, operating by peripheral release of renin (the renal dipsogen) and direct action of ang Elliotensin on the brain.
TL;DR: It is indicated that extracellular Mg++ not only differentially affects drug-induced contractions of vascular smooth muscle, but tissue contents of Ca++ and Mg++; as well as hypermagnesemia induced relaxation.
Abstract: ALTURA, BURTON M., AND BELLA T. ALTURA. hjhewe of magmsium on drug-induced contractions and ion content in rabbit aorta. Am. J. Physiol. 220(4) : 938-944. 197 1 .-In vitro studies using rabbit aortic strips were undertaken to determine the effects of the presence and absence of 1.2 mu magnesium (MS++) on I) contractiIe responses induced by seven different vasoactive agents and hormones, and 2) total tissue calcium (Ca++), Mg++, sodium @a+), potassium (K+), and water contents. The effects of hypermagnesemia were also explored. Mg++-free medium shifted the log dose-response curves (DRC) for acetylcholine, K+, and angiotensin to the left and resulted in potentiation of maximum responses. Similar experimental conditions shifted the DRC for epinephrine to the right concomitant with a marked loss in maximum response. DRC for histamine and serotonin were not affected by Mg++-free medium. Mg ++-free medium decreased tissue Mg++ content by 40 yO and increased Ca++ by 15 TO. Na+, K+, and water content were not affected, Hypermagnesemia induced relaxation. These data indicate that extracellular Mg++ not only differentially affects drug-induced contractions of vascular smooth muscle, but tissue contents of Ca++ and Mg++ as well.
TL;DR: It is proposed that high levels of circulating angiotensin II may contribute to the development of renal hypertension in man, and that the ability of the diseased kidney to compensate for the pressor effects of high angiotENSin levels by adjusting sodium and fluid balance may be an additional determining factor in theDevelopment of hypertension associated with renal disease.
TL;DR: A synthetic bradykinin-potentiating pentapeptide has been found to block in-vivo conversion of ang Elliotensin I to the active hypertensive peptide angiotensin II in rats and promoted hypotension only in those hypertensive animals in which the renin-angiotens in system is likely to be overactive.
TL;DR: The acute effect of angiotensin II on plasma cortisol, aldosterone and immunoassayable ACTH (I-ACTH) was studied in normal subjects and in 3 patients with hypopituitarism.
Abstract: The acute effect of angiotensin II on plasma cortisol, aldosterone and immunoassayable ACTH (I-ACTH) was studied in normal subjects and in 3 patients with hypopituitarism. Angiotensin II, in a pressor dose given by constant infusion for 1 hr, increased plasma aldosterone to 28.5 ±5 (sd) ng/100 ml, while ACTH had a significantly greater effect, increasing aldosterone to 64 ±10 mean ±(sd) ng/100 ml. ACTH (0.1 μg/kg/hr, βl–24) increased cortisol 3- to 4- fold; however, angiotensin II in a subpressor dose did not increase cortisol. A pressor dose of angiotensin significantly increased I-ACTH from 27.8 ±8.8 (sd) to 60.4 ±20 (sd) pg/ml (p<0.01). A rise was noted in every angiotensin infusion despite an apparent fall in cortisol whether administered in the morning or afternoon. In contrast, a subpressor infusion (1/3 pressor dose), or a pressor infusion of angiotensin after an overnight dexamethasone dose (1 mg q 12 hr), did not increase the plasma I-ACTH. In 3 patients with pituitary insufficiency, who...
TL;DR: Autoradiography of the brain indicated that angiotensin penetrates into the cerebrospinal fluid from the blood, and the volume of distribution was significantly larger than the plasma volume but smaller than thevolume of distribution of inulin.
TL;DR: Ferreira et al. as discussed by the authors synthesized a bradykinin potentiating peptide from Bothrops jararaca venom, which had the same spectrum of pharmacological properties as previously reported for Bradykinin Potentiating Factor.
TL;DR: The results suggest that the nonanesthetized rat is a good subject for physiologic and pharmacologic studies of the renin-angiotensin system.
Abstract: PETTINGER, WILLIAM A., MARY MARCHELLE, AND LORAINE A~GUSTO. Renin suppression by DOC and NaCl in the rat. Am. J. Physiol. 221(4) : 1071-1074. 197 1 .-Endocrine and dietary changes known to alter plasma renin activity (PRA) were studied in the nonanesthetized rat. Deoxycorticosterone (DOC) suppressed PRA by 90-95%. Ingestion of a low-sodium diet elevated PRA from a mean control value of 120 to 530 rig/l 00 ml per hr. This elevation was diminished or reversed by increments of sodium in the drinking water. Thus, changes in PRA in the rat are qualitatively similar to those in other species. Sodium pentobarbital and ether anesthesia increased PRA to levels similar to anesthesia control values reported by other investigators using these agents in their standard experimental procedure. Thus, normal levels (approximately 100 ng/lOO ml per hr) of PRA in the unanesthetized rat appear to be much lower than reported in the anesthetized rat. Ether and sodium pentobarbital anesthesia also abolished the depression of PRA induced by administration of DOC and sodium. This artifactual elevation of plasma renin, and thus angiotensin, activity by anesthetic agents can explain: I) the previously reported failure of DOC to suppress renin activity in the rat (9), and 2) the limited aldosterone secretory response to angiotensin in the anesthetized rat. These results suggest that the nonanesthetized rat is a good subject for physiologic and pharmacologic studies of the renin-angiotensin system.
TL;DR: It is demonstrated that the estrogen-induced rises in plasma renin substrate and renin activity during contraceptive therapy result in high circulating levels of angiotensin II, and confirmatory evidence for the concept that the concomitant suppression of renin secretion i...
Abstract: During treatment with estrogenprogestogen oral contraceptive preparations, blood levels of angiotensin II measured by radioimmunoassay were elevated to three times the normal value. This marked rise in blood angiotensin II occurred within five days of commencing treatment, persisted during oral contraceptive therapy for three months, and fell to normal levels after cessation of treatment. Plasma renin activity and renin substrate showed similar elevations during treatment, and were significantly correlated with the levels of blood angiotensin II. Plasma renin concentration fell significantly during treatment, to about 50% of the control value, and was inversely correlated with the blood angiotensin II level. These observations demonstrate that the estrogen-induced rises in plasma renin substrate and renin activity during contraceptive therapy result in high circulating levels of angiotensin II, and provide confirmatory evidence for the concept that the concomitant suppression of renin secretion i...
TL;DR: The cross-tachyphylaxis and DMAE studies suggest that several of the analogues and angiotensin II are interacting with a common adrenal medullary receptor.
Abstract: A structure-activity relationship study was attempted to determine the structural specificity of the no. 8 amino acid residue of [1-asp,5-ileu]-angiotensin II for adrenal medullary stimulation. Isolated cat adrenal glands were perfused retrograde at a flow rate of 1 ml/min with phosphate-buffered Locke's solution at 23 to 25 C. Continuous catecholamine analysis was performed using an automated trihydroxyindole procedure. All drugs were administered either by single injection (0.05 to 0.1 ml) or by perfusion. Angiotensin analogues studied were: [8-(OMe)tyr]-angiotensin II; [8-tyr]-angiotensin II; [8-ala]-angiotensin II; [5-ileu,8-(3-amino-4-phenylbutyric acid)]-angiotensin II (referred to as [8-APB]-angiotensin II); [5-ileu,8-(DL-3-amino-3'-phenylisobutyric acid)]-angiotensin II (referred to as [8-APIB]-angiotensin II); [1-asp(NH2),5-val]-angiotensin II; [1-asp,5-ileu]-angiotensin I; tetradecapeptide.
Three peptides (angiotensin II, [8-tyr]-angiotensin II, and [8-ala]-angiotensin II) were studied in vivo for stimulation of adrenal catecholamine secretion. For maximum pressor activity, angiotensin must be an octapeptide with an aromatic amino acid and free COOH group in the no. 8 position. None of these three are structural requirements in adrenal chromaffin tissue. There was cross-tachyphylaxis between angiotensin II and all the analogues studied except two ([8-APB]- and [8-APIB]-angiotensin II).
In vitro studies with 10-leu-C14-angiotensin I and angiotensin II antibody indicated that angiotensin I has a marked, direct stimulatory effect on the adrenal medulla. Adrenal medullary catecholamine secretion induced by angiotensin I and II was greatly potentiated by DMAE perfusions. Responses to nicotine were blocked by DMAE and bradykinin-induced catecholamine release was unchanged. The cross-tachyphylaxis and DMAE studies suggest that several of the analogues and angiotensin II are interacting with a common adrenal medullary receptor.
TL;DR: The results indicate involvement of adrenergic receptors in central vagus activity in pentobarbital anaesthetized dogs pretreated with the β-blocking agent Ko 592, and this effect was significantly antagonized by phentolamine.
TL;DR: The effects of moderate degrees of hypercapnia in hypoxia and in hyperoxia on the baroreceptor‐cardiodepressor reflex have been studied in nine normal men.
Abstract: 1. The effects of moderate degrees of hypercapnia in hypoxia and in hyperoxia on the baroreceptor-cardiodepressor reflex have been studied in nine normal men.2. The beat-by-beat relation between pulse interval (I) and systolic pressure (P) during transient elevations of arterial pressure induced by intravenous injections of angiotensin II and phenylephrine was used to assess the sensitivity (DeltaI/DeltaP) and setting (I at a single reference arterial pressure) of the reflex.3. There was no consistent change in reflex sensitivity in any of the conditions studied.4. In hyperoxia (P(A, O2) approximately 200 torr) hypercapnia was associated with significant re-setting of the reflex in the direction of tachycardia. The extent of the re-setting was correlated with the degree of hypercapnia and with the accompanying increase in breathing.5. When hyperoxia with hypercapnia was replaced by hypoxia (P(A, O2) approximately 55 torr) with hypercapnia (which causes substantial arterial chemoreceptor activity), pulse interval at constant arterial pressure was further decreased.6. The tachycardia of hypoxia could not be accounted for by change of arterial pressure, P(A, CO2) or pulmonary ventilation, since it was most clearly demonstrable at constant values of pressure and either P(A, CO2) or ventilation.