A novel effect of angiotensin on renal sympathetic nerve activity in mice.

Abstract

The goals of this study were to characterize the effects of angiotensin II (Ang II) on renal sympathetic nerve activity (RSNA) and to define mechanisms of its actions in mice. The experiments were performed in sodium pentobarbital anesthetized C57BL/6J mice to investigate the effects of intravenous administration of Ang II on RSNA recorded from renal sympathetic post-ganglionic nerve fibers. Intravenous (i.v.) administration of Ang II (4 ng/g) increased arterial pressure and evoked a biphasic change in RSNA: inhibition of high-amplitude phasic bursts of RSNA secondary to the initial rise of arterial pressure followed by activation of low-amplitude continuously discharging RSNA that exceeded baseline activity (255 +/- 72% baseline, n = 8). The peak change of mean arterial pressure (MAP) was +60 +/- 4 mmHg (n = 8). In the same group of animals, norepinephrine (40 ng/g) caused an equivalent increase in MAP (+57 +/- 5 mmHg) and essentially abolished RSNA. The Ang II-induced activation of RSNA was dose-dependent (0.5-4 ng/g, n = 7) and was abolished by the Ang II type 1 (AT1) receptor blocker, losartan (10 microg/g, i.v.) (301 +/- 61 versus 117 +/- 22% baseline, before versus after losartan, n = 5). The ganglionic blocker, hexamethonium (30 microg/g, i.v.), eliminated baseline high-amplitude bursts of RSNA but did not blunt the Ang II-induced RSNA (n = 6). In baroreceptor denervated and vagotomized mice, Ang II failed to inhibit high-amplitude bursts of RSNA but continued to trigger low-amplitude continuous RSNA. We conclude that Ang II activates renal sympathetic nerves that discharge in a continuous pattern, distinctly different than the normal baseline high-amplitude bursts of RSNA. The mechanism may involve direct activation of post-ganglionic sympathetic neurons mediated through AT1 receptors.