Attenuation by captopril of pressor responses to sympathetic stimuli: effects of procedures reducing activity of the renin-angiotensin system.
Low doses (0.1-1.0 mg/kg) of the converting enzyme inhibitor captopril given intravenously to pithed rats were followed by long lasting falls in systolic and diastolic arterial blood pressures. Concomitantly pressor responses were reduced to either electrical stimulation of the thoraco-lumbar sympathetic outflow or intravenous injection of the ganglion stimulant McNeil-A-343. Positive chronotropic responses of the heart to cardiac nerve stimulation were unchanged after relatively large doses of the drug (3.0 mg/kg). The reductions in arterial blood pressure and pressor responses to McNeil-A-343 caused by captopril persisted following beta-adrenoreceptor blockade, renal sympathectomy or unilateral nephrectomy, but did not occur after acute bilateral nephrectomy nor during sodium and water retention due to unilateral nephrectomy plus subacute administration of desoxycorticosterone and saline. Pressor responses to noradrenaline were reduced after 1.0 mg/kg captopril i.v. whereas those to methoxamine or vasopressin were unaltered after 5.0 mg/kg. It is concluded that in the rat, after elimination of sympathetic tone by pithing, the level of the arterial blood pressure and the magnitude of pressor responses to peripheral sympathetic nerve activation depend on the basal activity of the renin-angiotensin system. This maintains sufficient angiotensin II production to ensure retention of some tone in resistance vessels together with presynaptic augmentation of noradrenaline output at a sympathetic postganglionic nerve endings. The latter effects are abolished after converting enzyme inhibition with captopril, consequent to reduced tissue levels of angiotensin II and perhaps potentiation of the actions of bradykinin.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology*; D004558:Electric Stimulation; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System; D013564:Sympathetic Nervous System / Q000502:physiology*
D011392:Proline; D002216:Captopril; D009638:Norepinephrine