Hypertension and the coronary circulation with special attention to endothelial regulation

Calcium channel antagonists are commonly used to treat chronic hypertension. Several studies of intact vascular tissues suggest that these agents may im­pair the production of the endothelium-derived re­laxing factor and alter endothelium-dependent vas­cular relaxation. These studies are difficult to interpret because the calcium channel antagonist may have direct effects on vascular smooth muscle. In our study, a chemiluminescence assay was used to measure the release of nitrogen oxides from bo­vine aortic endothelial cells (BAEC) grown in mon­olayer. Under basal conditions, the release of nitro­gen oxides was 0.2 nmol/100 mg protein and was increased approximately two-fold by 0.1 //g brady­kinin. Incubations with diltiazem, verapamil, and nifedipine for 60 min did not influence the basal and bradykinin-stimulated release of nitrogen oxides by BAEC. These data illustrate that the pro­duction of the endothelium-derived relaxing factor is not altered by the calcium channel antagonist, and are compatible with an absence of L-type cal­cium channels in vascular endothelial cells. Chronic hypertension produces myriad adverse effects in the coronary circulation. After coronary occlusion, infarct size, expressed as a function of myocardial mass perfused, is increased by 33%, and the wavefront of infarction from subendocardium to subepicardium is hastened. Both chronic and acute hypertension produce numerous abnormali­ties of coronary flow regulation. These include im­pairments of autoregulation, changes in vascular responsiveness, and alterations of endothelial cell function. Many of these may worsen the clinical consequences of ischemic heart disease, either by producing structural alterations of the coronary vasculature, or equally importantly, by altering coronary vascular responsiveness to either mechan­ical or neurohumoral stimuli. A goal of the treat­ment of hypertension should not only be to lower blood pressure and reverse cardiac hypertrophy, but to correct these important vascular abnormali­ties.