Calcium antagonists and endothelial function: focus on nitric oxide and endothelin.
This paper reports on some interactions of calcium antagonists with nitric oxide and endothelin. It reviews evidence showing that the vasorelaxant action of calcium antagonists is facilitated by nitric oxide and describes the mechanism of this modulation. The interaction of calcium antagonists with endothelin is examined considering functions and production of the peptide. Among the functions examined, attention is drawn to the potentiation of responses to vasoconstrictors evoked by low threshold concentrations of endothelin, an action that could be important in pathology. The production of endothelin is increased by a high-salt diet in spontaneous hypertensive stroke-prone rats, this increased production, related to the overexpression of prepro ET-1mRNA, is responsible for cardiovascular hypertrophy and is blunted, in a blood pressure-unrelated manner, by the calcium antagonist lacidipine. At the same dosage regimen, lacidipine inhibits the hypertrophy of the cardiovascular system evoked by a high-salt diet.
Godfraind
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Laboratoire de Pharmacologie, Université Catholique de Louvain, Brussels, Belgium.
Salomone
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D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology; D019332:Endothelin-1 / Q000235:genetics*; D004730:Endothelium, Vascular / Q000187:drug effects*; D015870:Gene Expression; D006801:Humans; D009569:Nitric Oxide / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017673:Sodium Chloride, Dietary / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D019332:Endothelin-1; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; C060285:lacidipine; D009569:Nitric Oxide