ENDOTHELIAL DYSFUNCTION AND HYPERTENSION

Vascular endothelial cells play a key role in cardiovascular regulatio n by producing a number of potent vasoactive agents, including the vas odilator molecule nitric oxide (NO) and the vasoconstrictor peptide en dothelin (ET)-1. A dysfunction of the vascular endothelium has been im plicated in the pathophysiology of a number of cardiovascular diseases , important among which is essential hypertension. Impairment of NO sy nthesis, or increased inactivation of NO by superoxide radicals, may a ccount for the increased peripheral vascular tone associated with hype rtension, as well as contribute to the clinical consequences of this c ondition, which include vascular hypertrophy, increased platelet and m onocyte adhesion to the endothelium, atherosclerosis, myocardial infar ction and stroke. Similarly, increased ET-1 synthesis, or increased sm ooth muscle sensitivity to ET-1, could account for many of the feature s of hypertension, including increased peripheral vascular tone and va scular hypertrophy. Modulation of endothelial function is, therefore, an attractive therapeutic option in the treatment of hypertension. Cal cium antagonists have been shown to enhance the effects of NO, and inh ibit those of ET-1, on vascular smooth muscle cells. In addition, calc ium antagonists have antiatherogenic and antioxidant properties and co uld, therefore, prove to be useful therapeutic agents in preventing so me of the important complications of hypertension. The long term effec ts on cardiovascular morbidity and mortality of the long-acting nifedi pine 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 antihypertens ive agent since the major studies of beta-adrenoceptor blockers or thi azide diuretics. The results of this study are awaited with considerab le interest.