Captopril interferes with neurogenic vasoconstriction in the pithed rat by angiotensin-dependent mechanisms.
Angiotensin is known to facilitate the activity of the sympathetic nervous system, and the purpose of the present study was to investigate the possibility that angiotensin converting enzymes (ACE) inhibitors may interfere with neurogenic vasoconstriction by interfering with this interaction between angiotensin and the nervous system. In a pithed rat preparation the vasoconstrictor responses to both nerve stimulation (1-30 Hz) and exogenous noradrenaline (10-500 ng) were reduced by the ACE inhibitors captopril (0.1 and 1 mg/kg) and SQ20881 (10 mg/kg), and by the angiotensin II antagonist [Sar1 Ala8]angiotensin II (4 micrograms/kg/min). Angiotensin II infusion reversed the inhibition caused by captopril, and bradykinin infusion (1 microgram/kg/min) had no effect on responses to either nerve stimulation or noradrenaline. In rats that had been bilaterally nephrectomized 18-24 h previously, [Sar1, Ala8]angiotensin II was without any effect on responses to either nerve stimulation or noradrenaline, while captopril was without effect on responses to nerve stimulation but still had a small effect in reducing responses to noradrenaline. These results show that ACE inhibitors interfere with neurogenic vasoconstriction by an angiotensin-dependent mechanism. ACE inhibitors could thus lower blood pressure by two separate angiotensin-dependent mechanisms--first by interfering with neurogenic vasoconstriction as outlined above, and second, by blocking the direct vasoconstrictor action of angiotensin II.
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000502:physiology; D002216:Captopril / Q000494:pharmacology*; D003655:Decerebrate State; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D009392:Nephrectomy; D009638:Norepinephrine / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D000804:Angiotensin II; D011392:Proline; D002216:Captopril; D001920:Bradykinin; D009638:Norepinephrine