Rational drug therapy based on understanding the pathophysiology of hypertension
Emmanuel L. Bravo, MDAddress reprint requests to E.L.B., Head, Endocrine/Hypertension Research Laboratory, Research Institute, The Cleveland Clinic Foundation, One Clinic Center, 9500 Euclid Avenue, Cleveland, Ohio, 44195-5069.
Increased peripheral vascular resistance is the hemodynamic hallmark of chronic hypertension. Evidence suggests that Ca2+ is vital in mediating vasoconstrictive mechanisms. Calcium channel blockers correct the specific arteriolar vasoconstrictive mechanism without unwanted compensatory actions. Human primary hypertension may also be related to volume variations in which renal influences contribute to elevated arterial pressure and diuretics may be necessary to control the hypertension. Patients in whom neurόgenic-mediated vasoconstriction predominates show increased catecholamine production and renin release. These patients can be treated with either α- or β-receptor blocking agents or with converting enzyme inhibitors. Recent biochemical and pharmacological advances and a clear understanding of cardiovascular physiology have allowed more rational and individualized therapy for hypertensive patients, using minimal numbers of drugs in their minimal effective doses. Long-term monotherapy is now possible for different subgroups because of the specific and selective actions of newer antihypertensive agents.