CALCIUM-ANTAGONISTS THEIR PHYSIOLOGICAL DIFFERENCES

Most symposia concerned with the therapeutic roles of calcium antagonists first emphasize their extreme structural, chemical, and pharmacological heterogeneity. However, following these considerations, clinical discussions usually suggest that these agents are clinically and physiologically similar. Thus, investigators acknowledge greater vasodilating and hypotensive capabilities of one or another compound and rank these potencies clinically, emphasizing similar physiological actions on the target organs of hypertensive disease. This discussion concerns differences among these agents with respect to their cardiovascular and renal effects. Although most calcium antagonists are potent vasodilators, and reduce arterial pressure through a fall in total peripheral resistance, not all have this general effect. For example, nimodipine has little antihypertensive effectiveness; it is used as a cerebrovascular vasodilator. Certain agents may have greater negative chronotropic and inotropic cardiac effects; others may be devoid of these actions and, in fact, may be associated only with reflect cardiac stimulation. Thus, verapamil has great negative chronotropic effects-its was approved initially for this action-and inotropic effects; nifedipine is at the other extreme, while diltiazem is moderate. Most of these compounds reduce cardiac mass, but they may not produce only left ventricular mass reduction. Recent experimental studies show a contemporaneous increase in right ventricular mass. Finally, whereas most of these compounds reduce renal vascular resistance, some, such as diltiazem, nitrendipine, and clindiazem increase renal blood flow while reducing glomerular hydrostatic pressure. These effects may relate to their ability to diminish proteinuria, which suggests potential for reversing hypertensive and diabetic nephropathy. Thus, the calcium antagonists are far more heterogeneous than other classes of antihypertensive agents in their physiological and clinical actions. These differences may be well suited to clinical selection and application as the physician attempts to combine drug action with disease mechanisms.