Blockade of endogenous angiotensin-(1-7) in the hypothalamic paraventricular nucleus reduces renal sympathetic tone

In this study, we tested the hypothesis that angiotensin-(1-7) [Ang-(1-7)] acting in the neurons of paraventricular hypothalamic nucleus (PVN) contributes to the maintenance of sympathetic activity and blood pressure. For this purpose, the effects of microinjection of the A-779, the receptor Mas antagonist, into the PVN on mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were evaluated. In rats anesthetized with urethane (1.2 to 1.4 g/kg IP), bilateral microinjections of A-779 (0.1 nmol) into the PVN resulted in a selective and significant decrease in RSNA (-26 +/- 6% versus -2 +/- 3% vehicle; saline 0.9%). The magnitude of the decrease in RSNA produced by A-779 was comparable to that observed after microinjection of muscimol (1 nmol; -26 +/- 4%), a powerful neuronal inhibitor. A higher dose of A-779 (1 nmol) caused a reduction in RSNA (-21 +/- 4%) that was comparable in magnitude to the reduction observed with the lower dose. When compared with vehicle solution, no significant changes in MAP or HR were observed with both doses of A-779 tested. A decrease in RSNA was also observed after microinjections into the PVN of the angiotensin II type 2 (AT(2)) receptor antagonist PD123319 (1 nmol; -18 +/- 4%). Microinjections of the AT(1) antagonist losartan but not CV 11974 reduced MAP without changing RSNA. These results suggest that Ang-(1-7) Mas receptors and AT(2) receptors in the PVN neurons play a role in mediating the tonic maintenance of RSNA.