EFFECTS OF ANGIOTENSIN-II AND ANGIOTENSIN-(1-7) ON THE RELEASE OF [H-3] NOREPINEPHRINE FROM RAT ATRIA

We examined the effects of angiotensin II (Ang II) and Ang-(1-7) on the release of [H-3]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 [H-3]norepinephrine was increased 50% by 3x10(-8) mol/L of either peptide. No further increase in [H-3]norepinephrine release was observed with peptide concentrations up to 3x10(-7) mol/L. This effect was completely blocked by the nonselective angiotensin receptor antagonist saralasin (1x10(-7) mol/L). The type 1 angiotensin receptor antagonist DuP 753 (1x10(-6) mol/L) entirely prevented the increases in [H-3]norepinephrine caused by Ang II and Ang-(1-7). On the other hand, the type 2 angiotensin receptor antagonist PD 123319 (1x10(-6) mol/L) prevented the increase in [H-3]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).