Cardiovascular effects of angiotensin-(1-7) in conscious spontaneously hypertensive rats.
In the present study, we reassessed whether angiotensin (Ang)-(1-7) can exert short- and long-term cardiovascular effects because there has been a resurgence of interest in this N-terminal heptapeptide fragment of Ang II. In particular, we studied 3 aspects relating to the reported cardiovascular effects of Ang-(1-7): does this peptide (1) potentiate the hypotensive effect of bradykinin in normotensive Wistar-Kyoto rats and spontaneously hypertensive rats (SHR), (2) cause a depressor effect after long-term treatment in SHR, and (3) contribute to the antihypertensive effects of angiotensin-converting enzyme inhibitors? In the first series of experiments, Ang-(1-7) failed 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 experiments, a 7-day intravenous infusion of Ang-(1-7) (24 microg x kg(-1) x h(-1)) decreased 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 that the Ang-(1-7) antagonist A-779 (24 microg x kg(-1) x h(-1) for 7 days) attenuated the depressor effect of Ang-(1-7) when given concurrently in a separate group of SHR (n=8). In the third series of novel experiments, the angiotensin-converting enzyme inhibitor perindopril was given in drinking water for 7 days (0.3 mg. kg(-1) x day(-1)), either alone (n=6) or combined with an intravenous infusion of A-779 (24 microg x kg(-1) x h(-1) for 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 against Ang-(1-7) playing a major role in blood pressure regulation.
Widdop
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Department of Pharmacology, Monash University, Clayton, Victoria, Australia. robert.widdop@med.monash.edu.au
Sampey
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Jarrott
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B
D000803:Angiotensin I; D000804:Angiotensin II / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004347:Drug Interactions; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007262:Infusions, Intravenous; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)