Effects of angiotensin II and angiotensin-(1-7) on the release of [3H]norepinephrine from rat atria.

Abstract

We examined the effects of angiotensin II (Ang II) and Ang-(1-7) on the release of [3H]norepinephrine elicited by nerve stimulation (2 Hz, 0.5 millisecond, for 2 minutes) in rat atria isolated with their cardioaccelerans nerves. The stimulation-induced release of [3H]norepinephrine was increased 50% by 3 x 10(-8) mol/L of either peptide. No further increase in [3H]norepinephrine release was observed with peptide concentrations up to 3 x 10(-7) mol/L. This effect was completely blocked by the nonselective angiotensin receptor antagonist saralasin (1 x 10(-7) mol/L). The type 1 angiotensin receptor antagonist DuP 753 (1 x 10(-6) mol/L) entirely prevented the increases in [3H]norepinephrine caused by Ang II and Ang-(1-7). On the other hand, the type 2 angiotensin receptor antagonist PD 123319 (1 x 10(-6) mol/L) prevented the increase in [3H]norepinephrine release elicited by Ang-(1-7) but not by Ang II. These results suggest that Ang-(1-7), like Ang II, could have a neuromodulatory function in rat atria via activation of specific angiotensin receptor subtypes, which could be the subtype 1 angiotensin receptor for Ang II and subtypes 1 and 2 for Ang-(1-7).