Preservation of renal function by angiotensin during chronic adrenergic stimulation.

Abstract

The purpose of the present study was to determine the role of angiotensin II (Ang II) in mediating renal responses to chronic intrarenal norepinephrine infusion. Norepinephrine was continuously infused for 5 days into the renal artery of unilaterally nephrectomized dogs at progressively higher daily infusion rates: 0.05, 0.10, 0.20, 030, and 0.40 /tg/kg/min. In three additional groups of dogs, norepinephrine infusion was repeated during chronic intravenous captopril administration to fix plasma Ang II concentration at 1) low levels (no Ang II infused), 2) high levels in the renal circulation (Ang II infused intrarenally at a rate of 1 ng/kg/min), and 3) high levels in the systemic circulation (Ang II infused intravenously at a rate of 5 ng/kg/min). In the control group of animals with intact renin-angiotensin systems, there were progressive increments in mean arterial pressure (from 96±4 to 141±6 mm Hg) and plasma renin activity (from 0.4±0.1 to 10.9 ±4.5 ng angiotensin I/ml/hr) and concomitant reductions in glomerular filtration rate and renal plasma flow to approximately 40% of control during the 5-day norepinephrine infusion period. In marked contrast, when captopril was infused chronically without Ang II, mean arterial pressure was 20-25 mm Hg less than that under control conditions, and the renal hemodynamic effects of norepinephrine were greatly exaggerated; by day 3 of norepinephrine infusion, both glomerular filtration rate (16±2% of control) and renal plasma flow (12±4% of control) were considerably lower than values in control animals (86±4% and 80±8% of control, respectively). Similarly, when a high level of Ang II was localized in the renal circulation during captopril administration, mean arterial pressure was depressed, and again there were pronounced renal responses to norepinephrine. Conversely, when Ang II was infused intravenously during captopril administration, mean arterial pressure was not reduced, and the glomerular filtration rate and renal plasma flow responses to norepinephrine were similar to those that occurred under control conditions. These findings indicate that the renin-angiotensin system prevents exaggerated renal vascular responses to chronic norepinephrine stimulation by preserving renal perfusion pressure. (Hypertension 1991;17:278-287)

Influence of endogenous angiotensin on the renovascular response to norepinephrine.

“…This indicates that at high levels of adrenergic stimulation, the renal vasoconstrictor effects of Ang II were diminished relative to those of NE. Based on the pronounced increases in PRA achieved at the highest infusion rates of NE used in the present study and our previous measurements of PRA during intrarenal NE infusion, 6 -13 ' 32 it is unlikely that the diminished role of Ang II in mediating the renal vasoconstriction at more intense degrees of renal adrenergic stimulation was due to an inability to achieve additional increments in Ang II. Rather, the diminished effects of Ang II on RBF, relative to those of NE, may be due to the differential sensitivity of preglomerular and postglomerular vessels to these vasoconstrictors.…”

“…In an earlier study, we found that chronic intravenous infusion of Ang II at the same hypertensive rate as used in the present study (5 ng/kg per minute) prevented captoprilinduced deterioration of renal function during infusion of NE into the renal artery over a period of several days. 6 The current findings indicate that even normal levels of Ang II prevent enhanced renovascular responses to acute adrenergic stimulation when captopril is administered chronically. In the absence of Ang II replacement, how might chronic captopril administration predispose the kidneys to excessive renal vasoconstriction during acute intrarenal NE infusion?…”

“…In previous studies, we observed that captopril enhanced the renovascular response to intrarenal infusions of NE that produced 20-40% reductions in renal plasma flow when the renin-angiotensin system was intact. 6 - 13 However, since renal plasma flow was determined only after hours to days of continuous renal adrenergic stimulation, the significance of these findings is unclear because it is uncertain that neurally induced reductions in RBF of this magnitude would be sustained for such long periods of time under either physiological or pathophysiological conditions. The present results, on the other hand, showed that severe renal ischemia may occur very abruptly during moderate increments in renal adrenergic stimulation when the renin-angiotensin system is chronically blocked with captopril.…”

“…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. 3 -13 In…”