Captopril attenuates adrenergic vasoconstriction in rat mesenteric arteries by angiotensin-dependent and -independent mechanisms.
1. Angiotensin-converting enzyme inhibitors can attenuate reflex sympathetic vasoconstriction in vivo. We have investigated the effects of captopril (SQ 14 225) on adrenergic vasoconstrictor mechanisms in isolated, Krebs-Ringer solution perfused, rat mesenteric arteries. 2. Low concentrations of captopril (2 X 10(-6) mol/l) did not alter the vasoconstrictor response evoked by sympathetic nerve stimulation. 3. Exogenous angiotensin I and II did not have a direct vasoconstrictor effect, but caused dose-related increases in the amplitude of responses induced by nerve stimulation. 4. The potentiating effect of angiotensin I was antagonized by captopril (6.7 X 10(8)-2 X 10(-6) mol/l) and by saralasin (10(-8) mol/l). The potentiating effect of angiotensin II was antagonized by saralasin only. 5. In the absence of exogenous peptides high concentrations of captopril (1 X 10(-4)-3 X 10(-4) mol/l) antagonized vasoconstrictor responses evoked by sympathetic nerve stimulation and exogenous noradrenaline, but not those evoked by potassium chloride. 6. These results indicate that captopril can have two types of inhibitory effect at the adrenergic neuro-effector junction. High concentrations antagonize responses to noradrenaline and nerve stimulation. This effect is independent of peptide hormones and is unlikely to occur in vivo. Lower concentrations block the local vascular conversion of angiotensin I into II. As angiotensin II is an important peripheral amplifier of adrenergic vasoconstriction, this effect will also reduce sympathetic vasoconstrictor tone. This latter interaction could explain the inhibitory effect of converting enzyme inhibitors on sympathetic reflexes.
D000320:Adrenergic Fibers / Q000502:physiology*; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000294:innervation; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D012504:Saralasin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D000804:Angiotensin II; D011189:Potassium Chloride; D000803:Angiotensin I; D011392:Proline; D002216:Captopril; D012504:Saralasin; D001920:Bradykinin; D009638:Norepinephrine