Endothelial dysfunction and hypertension.
Vascular endothelial cells play a key role in cardiovascular regulation by producing a number of potent vasoactive agents, including the vasodilator molecule nitric oxide (NO) and the vasoconstrictor peptide endothelin (ET)-1. A dysfunction of the vascular endothelium has been implicated in the pathophysiology of a number of cardiovascular diseases, important among which is essential hypertension. Impairment of NO synthesis, or increased inactivation of NO by superoxide radicals, may account for the increased peripheral vascular tone associated with hypertension, as well as contribute to the clinical consequences of this condition, which include vascular hypertrophy, increased platelet and monocyte adhesion to the endothelium, atherosclerosis, myocardial infarction and stroke. Similarly, increased ET-1 synthesis, or increased smooth muscle sensitivity to ET-1, could account for many of the features of hypertension, including increased peripheral vascular tone and vascular hypertrophy. Modulation of endothelial function is, therefore, an attractive therapeutic option in the treatment of hypertension. Calcium antagonists have been shown to enhance the effects of NO, and inhibit those of ET-1, on vascular smooth muscle cells. In addition, calcium antagonists have antiatherogenic and antioxidant properties and could, therefore, prove to be useful therapeutic agents in preventing some of the important complications of hypertension. The long term effects on cardiovascular morbidity and mortality of the long-acting nifedipine gastrointestinal therapeutic system (nifedipine GITS) used in the treatment of essential hypertension are currently being investigated in the first multinational outcome study (INSIGHT) of an antihypertensive agent since the major studies of beta-adrenoceptor blockers or thiazide diuretics. The results of this study are awaited with considerable interest.
Ferro
C J
CJ
Clinical Pharmacology Unit, University of Edinburgh, Western General Hospital, Scotland.
Webb
D J
DJ
D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D016232:Endothelins / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology
D002121:Calcium Channel Blockers; D016232:Endothelins; D009569:Nitric Oxide