CALCIUM-ANTAGONISTS AND ENDOTHELIAL FUNCTION - FOCUS ON NITRIC-OXIDE AND ENDOTHELIN

This paper reports on some interactions of calcium antagonists with ni tric oxide and endothelin. It reviews evidence showing that the vasore laxant action of calcium antagonists is facilitated by nitric oxide an d describes the mechanism of this modulation. The interaction of calci um antagonists with endothelin is examined considering functions and p roduction of the peptide. Among the functions examined, attention is d rawn to the potentiation of responses to vasoconstrictors evoked by lo w threshold concentrations of endothelin, an action that could be impo rtant in pathology. The production of endothelin is increased by a hig h-salt diet in spontaneous hypertensive stroke-prone rats, this increa sed production, related to the overexpression of prepro ET-1mRNA, is r esponsible for cardiovascular hypertrophy and is blunted, in a blood p ressure-unrelated manner, by the calcium antagonist lacidipine. At the same dosage regimen, lacidipine inhibits the hypertrophy of the cardi ovascular system evoked by a high-salt diet.