Role of calcium antagonists in systemic hypertension

Despite the physiologic rationale of their use in hypertension, traditional vasodilators such as hydralazine and minoxidil are often relegated to the second and, more often, to the third and fourth steps of step-care programs. Although they are powerful blood pressure-lowering agents, they cause tachycardia, excessive renin stimulation and sodium retention, and cannot be used as the only antihypertensive agent. The characteristics of the antihypertensive action of calcium antagonists make them suitable for monotherapy. Indeed, all calcium antagonists, while effectively lowering blood pressure through vasodilatation, either do not affect heart rate (verapamil and its analogs) or cause a moderate and transient heart rate increase (dihydropyridine compounds). Dihydropyridines also possess a natriuretic effect, probably due to inhibition of tubular sodium transport. The natriuretic effect is evident during the first 2 days of administration, but a small negative sodium balance persists for at least 1 week. There is no increase in body weight or fluid volumes with long-term administration of calcium antagonists with a marked acute natriuretic response, such as dihydropyridines, and those antagonists with a very moderate immediate natriuretic response, such as verapamil. All calcium antagonists, therefore, appear capable of preventing the sodium and water retention that vasodilatation would otherwise entail. More liberal step-care guidelines are now possible to find the agent most suitable for the individual patient. In these guidelines, calcium antagonists, as well as angiotensin converting enzyme inhibitors, are considered as possible first-choice agents along with diuretics and β blockers.