Cardiovascular effects of angiotensin-(1-7) in conscious spontaneously hypertensive rats

In the present study, we reassessed whether angiotensin (Ang)-(1-7) can exe rt short- and long-term cardiovascular effects because there has been a res urgence of interest in this N-terminal heptapeptide fragment of Ang II. In particular, we studied 3 aspects relating to the reported cardiovascular ef fects of Ang-(1-7): does this peptide (1) potentiate the hypotensive effect of bradykinin in normotensive Wistar-Kyoto rats and spontaneously hyperten sive rats (SHR), (2) cause a depressor effect after long-term treatment in SHR, and (3) contribute to the antihypertensive effects of angiotensin-conv erting enzyme inhibitors? In the first series of experiments, Ang-(1-7) fai led to enhance the dose-related hypotensive responses evoked by bradykinin in SHR (n=11) and Wistar-Kyoto (n=5) rats. In the second series of experime nts, a 7-day intravenous infusion of Ang-(1-7) (23 mu g . kg(-1) . h(-1)) d ecreased blood pressure in SHR (n=12) on days 4 and 5, although this effect waned despite continual Ang-(1-7) infusion. However, a new finding was tha t the Ang-(1-7) antagonist A-779 (24 mu g . kg(-1) . h(-1) for 7 days) atte nuated the depressor effect of Ang-(1-7) when given concurrently in a separ ate group of SHR (n=8). In the third series of navel experiments, the angio tensin-converting enzyme inhibitor perindopril was given in drinking water for 7 days (0.3 mg . kg(-1) . day(-1)), either alone (n=6) or combined with an intravenous infusion of A-779 (24 mu g . kg(-1) . h(-1) fur 7 days, n=8 ). Although this dose of A-779 attenuated the depressor effect of Ang-(1-7) , it did not alter the antihypertensive effect caused by perindopril. Thus. the present results contrast with a number of previous studies and argue a gainst Ang-(1-7) playing a major role in blood pressure regulation.