Influence of endogenous angiotensin on the renovascular response to norepinephrine.

Abstract

The purpose of this study was to elucidate the role of endogenous angiotensin II in mediating the renovascular effects of renal adrenergic stimulation. Six conscious dogs instrumented for monitoring of renal blood flow were subjected to step increases every 10 minutes in the rate of norepinephrine infusion into the renal artery. Under control conditions, infusion of norepinephrine (10-40 ng/min per milliliter per minute of control renal blood flow) increased plasma renin activity and decreased renal blood flow progressively by -10-75%. When increments in angiotensin II during norepinephrine infusion were abolished by fixing plasma levels of angiotensin II at either normal or high concentrations by chronic infusion of captopril plus angiotensin II, renal blood flow responses to adrenergic stimulation were greatly attenuated at rates of norepinephrine infusion that decreased renal blood flow up to -40% under control conditions. Thus, acutely generated angiotensin II appeared to contribute to the renovascular effects of norepinephrine. However, when endogenous levels of angiotensin II were suppressed to low levels by chronic infusion of captopril alone, norepinephrine induced severe renal ischemia at much lower rates of infusion than occurred when the renin-angiotensin system was intact. Since this enhanced sensitivity to norepinephrine did not occur during chronic captopril infusion when angiotensin II was given simultaneously at rates that restored mean arterial pressure to normotensive levels or higher, low arterial pressure during chronic captopril administration may predispose the kidneys to excessive renal vasoconstriction during renal adrenergic stimulation. Because both norepinephrine (NE) released from adrenergic nerve terminals and angiotensin II (Ang II) generated in response to renal nerve stimulation have potent direct effects on renal hemodynamics and sodium excretion, blockers of the renin-angiotensin system have been given in a number of studies to determine the contribution of increased Ang II generation to the renal hemodynamic and antinatriuretic effects of renal adrenergic stimulation. The most consistent finding from these studies has been that Ang II, presumably by preferentially constricting the efferent arterioles, plays a significant role in the maintenance of glomerular filtration rate during reductions in renal blood flow (RBF) produced by neural stimulation. 3 " 6 The role of generated Ang II in mediating the RBF and sodium excretory responses produced byTenal adrenergic stimulation, however, has been more controversial.

Influence of angiotensin on the early progression of heart failure

“…However, the decrease in cardiac output by almost 50% during pacing would be expected to produce a less than twofold increase in plasma ANG II concentration. Although not investigated in the present study, elevations in plasma levels of ANG II of this magnitude have very little or no effect on systemic or renal hemodynamics, sodium excretion, drinking, or neurohormonal activation in normal dogs (3,16,35,36,44). Furthermore, if sustained increments in plasma levels of ANG II on days 1-8 of pacing had contributed to the above responses, we would not have expected all of the measured responses during this initial period of pacing to be quantitatively comparable to those in paced dogs with a functional renin-angiotensin system, normal PRA under basal conditions, and possibly even episodic exacerbations in renin secretion and plasma levels of ANG II during periods of activity (28).…”

Epigenetics and Hypertension

“…The RAS, one of the main controllers of systemic blood pressure, can contribute to systemic hypertension in humans by exaggerating vasopressor responses to drugs [30], nutrients [31], or exercise [32]. One study, using 3 days of water deprivation in pregnant rats, reported increments in fetal plasma sodium concentration and osmolality in association with increments in fetal liver angiotensinogen mRNA and plasma angiotensin I and angiotensin II levels [33•].…”

Vasopressin Therapy for Vasoplegic Syndrome Following Cardiopulmonary Bypass

“…Weaning the alpha‐adrenergic agents before vasopressin infusion was purposely attempted since the response to norepinephrine is substantially reduced in patients with chronic congestive failure, due to down‐regulation of receptors 22 . This weaning is also desirable to minimize the detrimental effects of prolonged norepinephrine infusion: a direct negative inotropic cardiac action due to up‐regulation of TNF‐α, 23 hepatic ischemia and hepatocellular dysfunction, 23 and renal ischemia due to enhanced adrenergic stimulation in the presence of chronically blocked renin‐angiotensin system 24 . None of the patients in this study developed complications related to vasopressin infusion.…”