EFFECT OF CAPTOPRIL ON SYMPATHETIC NEUROTRANSMISSION IN PITHED NORMOTENSIVE RATS

Abstract Captopril significantly diminished the basal diastolic blood pressure and the vasopressor response to electrical stimulation of the thoracic-lumbar spinal cord in pithed normotensive rats. The reduction of the hypertensive response to electrical stimulation was more pronounced after bilateral adrenalectomy. Captopril also diminished the vasopressor response to intravenously administered (−)-noradrenaline. Pretreatment of the animals with indomethacin had no effect on the vasopressor response to electrical stimulation and did not affect the sympathoinhibition of captopril. After bilateral nephrectomy, 18–24 h previously, the basal diastolic blood pressure and the vasopressor response to electrical stimulation were reduced and captopril had no additional inhibitory effect on these parameters. In indomethacin-pretreated animals with intact kidneys, restoration of the basal diastolic blood pressure with angiotensin II (AII) completely abolished the sympathodepressive effect of captopril. When the reduction in basal diastolic blood pressure with captopril was prevented by vasopressin, converting enzyme inhibition had no depressive effect on the hypertensive response to intravenously administered (−)-noradrenaline and did not invluence sympathetic neurotransmission in animals with intact adrenals. However, a small, but significant reduction of the hypertensive response to electrical stimulation by captopril was still detectable in bilaterally adrenalectomized rats. The results suggest that endogenous AII facilitates sympathetic neurotransmission in vascular smooth muscle of pithed normotensive rats. However, the modulatory action of endogenous AII largely results from an effect on basal arteriolar smooth muscle tone and should, therefore, be considered as non-specific facilitation. Genuine prejunctional facilitation of the sympathetic neurotransmission in vascular smooth muscle can only be observed after bilateral adrenalectomy but this effect of endogenous AII appears of minor significance, at least in pithed normotensive rats.