Strategies in antihypertensive therapy: implications of the kidney

Because we so rarely know the cause of hypertension, antihypertensive therapy remains empiric. However, certain principles of treatment are emerging; one of these concerns the critical role of the kidney in antihypertensive therapy. Whether or not the kidney is primarily responsible for hypertension in a patient, it is the patient's renal response to treatment that determines, to a major degree, an agent's efficacy. Vasodilators have been a conceptually attractive approach to the treatment of high blood pressure, because they decrease total peripheral resistance, which is considered to be the mechanism responsible for this condition in most patients. Nonspecific vasodilators exert a series of actions on the kidney--including profound sodium retention and reactive renin release--that limits therapeutic response. For reasons that are not yet clear, but are apparently related to specific action on calcium entry into vascular smooth muscle, endocrine function, and renal hemodynamics, calcium channel blocking agents, such as nifedipine, have an advantage in the treatment of hypertension. They cause little or no sodium retention; thus, the addition of a diuretic agent is not required. In fact, there is evidence that sodium loading in certain patients may potentiate the antihypertensive efficacy of these drugs. The renin-angiotensin system seems to be activated to a somewhat lesser degree by calcium channel blocking agents than it is by nonspecific vasodilators; in addition, these agents interfere with the actions of angiotensin on aldosterone release. Moreover, their dilator action on the renal blood supply favors sodium excretion. Nifedipine either has no effect on the renal blood supply or induces an increase in renal blood flow and maintains glomerular filtration rate, both of which combine to support the ensuing natriuresis.