Nerve-Mediated Antidiuresis and Antinatriuresis After Air-Jet Stress Is Modulated by Angiotensin II

Abstract

A putative interaction between angiotensin II (Ang II) and the sympathetic nervous system within the kidney has been reported. We tested the hypothesis in conscious rats that endogenous Ang II modulates the renal effects of a stress-induced increase in sympathetic nerve activity. We recorded mean arterial blood pressure, heart rate, renal sympathetic nerve activity, renal hemodynamics, urine volume, and urinary sodium content in conscious rats. We used the Ang II type 1 receptor blocker ZD 7155 to inhibit the effects of endogenous Ang II. Ten minutes of air-jet stress increased renal sympathetic nerve activity by 98 +/- 4% (n = 6) without changing systemic hemodynamics. Air-jet stress reduced urine volume (from 31 +/- 3 to 8 +/- 4 microL/min per gram kidney weight, P < .05, n = 12) and sodium excretion (from 4.3 +/- 0.9 to 1.2 +/- 0.3 mumol/min per gram kidney weight, P < .05, n = 12). After renal denervation, air-jet stress had no effect on either parameter. Six micrograms of the Ang II type 1 receptor inhibitor ZD 7155 blunted the decrease in urine volume and sodium excretion in response to air-jet stress, although the increase in renal sympathetic nerve activity during air-jet stress and the pressor response to exogenous Ang II were not affected. Glomerular filtration rate and renal plasma flow were also not affected. Higher doses of 30 and 60 micrograms ZD 7155 inhibited the pressor response to exogenous Ang II and abolished the changes in urine volume and sodium excretion in response to air-jet stress. None of the ZD 7155 doses affected urinary sodium excretion permanently. Hence, the Ang II type 1 receptor antagonist ZD 7155 impaired or abolished the renal nerve-mediated antinatriuresis and anitidiuresis in response to air-jet stress. We conclude that endogenous Ang II modulates the renal effects of centrally mediated changes of sympathetic nerve activity in conscious rats.

Effects of sympathetic nerves and angiotensin II on renal sodium and water handling in rats with common bile duct ligature

“…If low amounts of angiotensin (inhibited by small amounts of an AT 1 inhibitor) are mandatory for the tubular effect of sympathetic impulses, it is conceivable that angiotensin under these circumstances acts for example on pre-and postsynaptic receptors without any further effect on salt and water reabsorption. Our previous data on rats subjected to air-jet stress support the idea of an interaction between RSNA and tubular angiotensin II in renal sodium and water handling (39). Furthermore, a recent paper demonstrated that renal nerve stimulation increased the effect of intraluminal angiotensin II on proximal tubule transport in rats, an effect that was attenuated by an ACE-inhibitor (32).…”

“…Although we cannot exclude additive effects of AT 1 and sympathetic outflow on volume retention, a specific interaction between AT 1 and sympathetic nerves appears more likely. Such an interaction could occur at peritubular sympathetic varicosities by AT 1 -mediated presynaptic stimulation of neurotransmitter release (36,39) or at the juxtaglomerular appara- Fig. 7.…”

“…The dosage of the AT 1 receptor antagonist ZD-7155 was previously proven to be only intrarenally effective (39). After two 15-min control periods, all rats were infused for 30 min with saline (10% body wt).…”

“…Integrated RSNA was expressed as millivolts per second per 1-s interval. The data are mainly expressed as percent change from control values according to the conventional evaluation of multifiber recordings (39). Besides presenting the RSNA data as line/scatter plots, we also calculated the "area under the curve" in some experiments by increasing the number of evaluated data points to 50 per RSNA recordings in each experimental group.…”

“…We could demonstrate in rats that the effects of increased renal sympathetic nerve activity (RSNA) on renal sodium and water excretion could be inhibited by very low doses of an angiotensin II AT 1 receptor inhibitor not interfering with systemic angiotensin II effects or renal hemodynamics (39). These results suggested a tonic, indispensable influence of angiotensin II on the intrarenal effects of increased sympathetic drive.…”