Angiotensin on Vascular Smooth Muscle

Bohr, David F.

doi:10.1007/978-3-642-65600-2_23

Cited by 41 publications

(24 citation statements)

References 39 publications

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“…Blood flows in the right ventricle, left ventricle, and kidneys were 210+22, 310+30, and 531±33 ml/100 g per min, respectively, before saline administration, and were 218±25,305±27, and 505±70 (14). This potentiation of adrenergic stimuli 2 20 by angiotensin probably is attributable to enhanced 0°5 45 0 synthesis and release, as well as to inhibition of neu-M/N/UTES ronal re-uptake, of norepinephrine at sympathetic nerve terminals (14,28,29). The present study shows IGURE 3 Changes in cardiac output, heart rate, mean aortic that the incals in plasm noe pinepn concentra- (27).…”

Section: Resultsmentioning

confidence: 56%

Renin-Angiotensin System Inhibition in Conscious Dogs during Acute Hypoxemia

Liang¹,

Gavras²

1978

J. Clin. Invest.

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A B S T R A C T The role of the renin-angiotensin system in mediating the circulatory and metabolic responses to hypoxia was studied in three groups of conscious dogs that were infused continuously with normal saline, teprotide (10 ug/kg per min), and saralasin (1 ,tg/kg per min), respectively. Hypoxia was produced by switching from breathing room air to 5 or 8% oxygen-nitrogen mixture. Plasma renin activity increased from 2.3+0.4 to 4.9±0.8 ng/ml per h during 8% oxygen breathing, and from 2.8±0.4 to 8.4+1.8 ng/ ml per h during 5% oxygen breathing. As expected, cardiac output, heart rate, mean aortic blood pressure, and left ventricular dPldt and dP/dtIP increased during both 5 and 8% oxygen breathing in the saline-treated dogs; greater increases occurred during the more severe hypoxia. Teprotide and saralasin infusion diminished the hemodynamic responses to 5% oxygen breathing, but did not affect the responses to 8% oxygen breathing significantly. In addition, the increased blood flows to the myocardium, kidneys, adrenals, brain, intercostal muscle, and diaphragm that usually occur during 5% oxygen breathing were reduced by both agents. These agents also reduced the increases in plasma norepinephrine concentration during 5% oxygen breathing, but had no effects on tissue aerobic or anaerobic metabolism.In dogs pretreated with propranolol and phentolamine, administration of teprotide (0.5 5% oxygen breathing reduced mean aortic blood pressure and total peripheral vascular resistance, and increased cardiac output and heart rate, but did not affect left ventricular dPldt, dPldtlP, and end-diastolic pressure. Simultaneously, renal and myocardial blood flows increased and myocardial oxygen extraction decreased, while myocardial oxygen consumption did not change significantly.These results suggest that the renin-angiotensin system plays an important role in the hemodynamic responses to severe hypoxia. It appears that angiotensin not only exerts a direct vasoconstrictor action, especially upon the coronary and renal circulations, but also potentiates the cardiovascular effects of sympathetic stimulation that occur during severe hypoxia. INTRODUCTIONIncreasing evidence has accumulated that hypoxia stimulates the renin-angiotensin system. Low oxygen tension increases the granularity of human juxtaglomerular cells cultured in vitro (1). Alveolar hypoxia in vivo also increases the number of granules ofjuxtaglomerular cells (2, 3), plasma renin activity (4, 5), plasma angiotensin II levels (6), and the angiotensin converting enzyme activity both in the lungs and in the serum (7). The mechanisms of renin release during hypoxia are not clearly elucidated. The increase in the granularity of juxtaglomerular cells (1)(2)(3) would suggest a direct action of hypoxia on renin release, but acute local renal perfusion with hypoxic blood did not increase the renin activity in renal venous blood (8). On the other hand, renin may be released by sympathetic discharge (9) produced by hypoxia. Furthermore, renal

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Section: Resultsmentioning

confidence: 56%

Renin-Angiotensin System Inhibition in Conscious Dogs during Acute Hypoxemia

Liang¹,

Gavras²

1978

J. Clin. Invest.

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“…We therefore performed experiments in four lungs (experiment 18) from rats pretreated with 6-hydroxydopamine and in two lungs from rats pretreated with reserpine (experiment 19), in which angiotensin II rather than KCl was given during normoxia and hypoxia.…”

Section: Methodsmentioning

confidence: 99%

Hypoxia Impairs Vasodilation in the Lung

Voelkel¹,

McMurtry²,

Reeves³

1981

J. Clin. Invest.

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A B S T R A C T Alveolar hypoxia causes pulmonary vasoconstriction; we investigated whether hypoxia could also impair pulmonary vasodilation. We found in the isolated perfused rat lung a delay in vasodilation following agonist-induced vasoconstriction. The delay was not due to erythrocyte or plasma factors, or to alterations in base-line lung perfusion pressure. Pretreating lungs with arachidonic acid abolished hypoxic vasoconstriction, but did not influence the hypoxiainduced impairment of vasodilation after angiotensin II, bradykinin, or serotonin pressor responses. Progressive slowing of vasodilation followed angiotensin IIinduced constriction as the lung oxygen tension fell progressively below 60 Torr. KCI, which is not metabolized by the lung, caused vasoconstriction; the subsequent vasodilation time was delayed during hypoxia. However, catecholamine depletion in the lungs abolished this hypoxic vasodilation delay after KCIinduced vasoconstriction. In lungs from high altitude rats, the hypoxia-induced vasodilation impairment after an angiotensin II pressor response was markedly less than it was in lungs from low altitude rats. We conclude from these studies that (a) hypoxia impairs vasodilation of rat lung vessels following constriction induced by angiotensin II, serotonin, bradykinin, or KCI, (b) hypoxia slows vasodilation following KCIinduced vasoconstriction probably by altering lung handling of norepinephrine, (c) the effect of hypoxia on vasodilation is not dependent on its constricting effect on lung vessels, (d) high altitude acclimation moderates the effect of acute hypoxia on vasodilation, and (e) the hypoxic impairment of vasodilation is possibly the result of an altered rate of dissociation of agonists from their membrane receptors on the vascular smooth muscle.

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“…To determine whether either of these humoral vasoconstrictors played an integral role in the hypoxic pressor response 13 -14 and therefore was not suitable as an independent reference agonist, we also performed experiments with saralasin acetate, l-Sar-8-Ala-angiotensin II acetate, a competitive inhibitor of angiotensin II, 1S and sodium meclofenamate, A/-(2,6-dichloro-w-tolyl)anthranate sodium, an inhibitor of prostaglandin synthesis. 18 …”

mentioning

confidence: 99%

Inhibition of hypoxic pulmonary vasoconstriction by calcium antagonists in isolated rat lungs.

McMurtry¹,

Davidson²,

Reeves³

et al. 1976

Circulation Research

350

147

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SUMMARY The role of a transmembrane calcium influx in hypoxic pulmonary vasoconstriction was studied in isolated, bloodperfused, rat lungs. We reasoned that, if the influx of extracellular calcium mediated the hypoxic mechanism, pressor responses to alveolar hypoxia (2.5% O 3 ) would be susceptible to inhibition by the calcium antagonists verapamil (2 x 10 5 to 2 x 10 ' HIM) and SKF 525 A (2.6 to 260 IDM). Susceptibility of hypoxic pressor responses to inhibition by these calcium antagonists was contrasted to that of pressor responses elicited by the humoral vasoconstrictors angiotensin II (1 or 0.5 fig) and prostaglandin F to (10 jig). Since neither saralasin (0.5 JJM), a competitive antagonist of angiotensin II, nor meclofenamate (6.8 HM), an inhibitor of prostaglandin synthesis, depressed hypoxic pressor responses, it was concluded that these humoral transmitters were not directly involved in the hypoxic mechanism, and therefore served as independent reference agonists. The order of susceptibility of pulmonary pressor responses to inhibition by verapamil was hypoxia > angiotensin II > prostaglandin F^. SKF 525A also reduced pressor responses to hypoxia more readily than those to angiotensin II. The greater inhibition of hypoxic pulmonary vasoconstriction by both calcium antagonists suggested that the hypoxic mechanism was critically dependent on the transmembrane influx of extracellular calcium. Mediation of the hypoxic response by this type of excitation-contraction coupling is consistent with the idea that hypoxia has a direct depolarizing effect on the vascular smooth muscle. It also provides a unifying explanation for inhibition of the hypoxic mechanism by various agents that have depressant or stabilizing actions on membranes in addition to other pharmacological effects.

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Angiotensin on Vascular Smooth Muscle

Cited by 41 publications

References 39 publications

Renin-Angiotensin System Inhibition in Conscious Dogs during Acute Hypoxemia

Renin-Angiotensin System Inhibition in Conscious Dogs during Acute Hypoxemia

Hypoxia Impairs Vasodilation in the Lung

Inhibition of hypoxic pulmonary vasoconstriction by calcium antagonists in isolated rat lungs.

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