New insights into the therapeutic mechanism of action of calcium channel blockers in salt-dependent hypertension: their interaction with endothelin gene expression.
It appears that the beneficial action of calcium channel blockers (CCBs) in hypertension may be related to short-term and long-term effects. This paper summarises pharmacological studies aiming to characterise those effects. The primary consequence of the short-term effects is the decrease of blood pressure related to a selective interaction of CCBs with calcium channels in hypertensive vessels. The long-term effects may additionally control the disease through prevention of end organ damage, accompanying the interaction of CCBs with the pathways, leading to the re-expression of embryonic genes and to the overactivation of type I collagen gene, which are amplified by a high-salt diet. ET-1 and tumour growth factor beta-1 could be among the main factors activating those pathways. The processes leading to overexpression of those factors and to tissue remodelling may be controlled by lacidipine, independent of the reduction of blood pressure.
Godfraind
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Laboratoire de Pharmacologie, Faculté de Médecine, Université Catholique de Louvain, Brussels, Belgium.
D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D016232:Endothelins / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D012965:Sodium Chloride / Q000009:adverse effects*
D002121:Calcium Channel Blockers; D016232:Endothelins; D012965:Sodium Chloride