Angiotensin-(1-7) significantly attenuated K+-induced norepinephrine release from the hypothalamus in spontaneously hypertensive rats via a bradykinin/NO-mediated mechanism.
Does Angiotensin-(1-7) inhibit norepinephrine release in the hypothalami of hypertensive rats?
Ang-(1-7) decreases norepinephrine release from the hypothalamus via Ang-(1-7) or AT2 receptors and a BK/NO/cGMP/PKG pathway, providing a mechanistic basis for its central antihypertensive effects.
Release of norepinephrine (NE) by the hypothalamic nuclei may contribute to regulation of sympathetic nervous system (SNS) activity. Angiotensin-(1-7) Ang-(1-7) has an antihypertensive effect and may decrease SNS activity. We tested the hypothesis that Ang-(1-7) inhibits the release of NE in hypothalami, via the Ang-(1-7) and angiotensin II type 2 (AT2) receptors, acting through a bradykinin (BK)/NO-dependent mechanism. Hypothalami from normotensive controls and spontaneously hypertensive rats (SHR) were isolated and endogenous NE stores labeled by incubating the tissues with 3HNE. 3HNE release from the hypothalami was stimulated by KCl in the presence or absence of Ang-(1-7) alone or combined with various antagonists and inhibitors. Ang-(1-7) significantly attenuated K+-induced NE release by hypothalami from normotensive rats but was more potent in SHR. The Ang-(1-7) receptor antagonist D-Ala7Ang-(1-7), the AT2 receptor antagonist PD 123319, and the BK B2) receptor antagonist icatibant all blocked the inhibitory effect of Ang-(1-7) on K+-stimulated NE release in SHR. The inhibitory effect of Ang-(1-7) disappeared in the presence of the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester and was restored by the precursor of NO, l-arginine. The diminished NE release caused by Ang-(1-7) was blocked by a soluble guanylyl cyclase inhibitor as well as by a cGMP-dependent protein kinase (PKG). We concluded that Ang-(1-7) decreases NE release from the hypothalamus via the Ang-(1-7) or AT2 receptors, acting through a BK/NO-mediated mechanism that stimulates cGMP/PKG signaling. In this way, Ang-(1-7) may decrease SNS activity and exert an antihypertensive effect.
Gironacci et al. (Tue,) conducted a other in Hypertension. Angiotensin-(1-7) vs. Absence of Ang-(1-7) was evaluated on K+-stimulated [3H]norepinephrine release from hypothalami. Angiotensin-(1-7) significantly attenuated K+-induced norepinephrine release from the hypothalamus in spontaneously hypertensive rats via a bradykinin/NO-mediated mechanism.