Calcium channel blockade with nifedipine reduces the systemic and the pulmonary vascular reactivity to adrenergic activation in hypertension.

In hypertension the systemic and the pulmonary circulation show exaggerated vascular tone and responsiveness to adrenergic stimuli. In 22 hypertensive men we tested whether the regulation of the two vascular beds is improved by calcium entry blockade with nifedipine. Mental arithmetic raised epinephrine plasma concentration (by 80%), cardiac output (CO) and blood pressure in both circuits, and caused systemic vasodilatation and pulmonary vasoconstriction. After the drug the epinephrine reaction was diminished (+20%), variations in CO and systemic blood pressure were almost unchanged and pulmonary vasoconstriction was abolished. A cold pressor test increased norepinephrine plasma concentration (by 24%), systemic and pulmonary pressure and resistance and did not alter CO. The norepinephrine response to cold was enhanced (+35%) by nifedipine, while systemic and pulmonary resistance rises were importantly attenuated (from +24% to +7% and from +41% to +1%, respectively), and greatly diminished the pressure reactivity. A sympatho-adrenal modulation by calcium blockade, per se, might have restrained the vasomotion during arithmetic. The impressive attenuation of the constrictor responses to cold, which was possibly associated with a potentiated sympathetic drive, prospects that the two circuits share a vascular contractile disorder in which calcium ions are involved.

Treatment of hypertension with calcium antagonists. Review.

Calcium channel blockers have a selective action on the cardiovascular system. They reduce the energy requirement of the heart, reduce vascular smooth muscle tone, and increase systemic blood flow. Vasodilatation occurs in both the systemic and the pulmonary systems to an extent proportional to the baseline level of vascular resistance, and results in reduction of blood pressure when it is elevated. Thus, these blockers are useful in patients with high blood pressure. Clinical experience of calcium channel blockers in hypertension is so far confined almost exclusively to verapamil and nifedipine. This article reviews the advantages and limitations of these two compounds, their acute hemodynamic effects in hypertensive subjects, and their use in the treatment of hypertensive emergencies, hypertensive encephalopathy, and pheochromocytoma, and as ventricular afterload reducing agents in hypertensive left ventricular failure. Similarities in the effects of nifedipine on systemic and pulmonary vascular tone are presented as evidence that altered intracellular Ca++ concentration is involved in the vasoconstriction seen in both systems in systemic high blood pressure. They also provide support for the hypothesis that inappropriate Ca++ handling may be involved in maintaining elevated blood pressure in human hypertension.

Treatment of hypertension with nifedipine, a calcium antagonistic agent.

Hemodynamic monitoring after a single dose (10 mg) of nifedipine in 27 primary hypertensive subjects (diastolic pressure greater than 110 mm Hg) documented that this calcium antagonistic agent exerts a potent arteriolar vasodilating action, which results in prompt (-21% of control at 30 minutes) and persistent (-16% of control at 120 minutes) fall in mean arterial pressure associated with a rise in cardiac output and pulse rate. The same patients received oral treatment for 3 weeks. Hourly pressure readings showed that 1) the antihypertensive response to each dose lasts 8--12 hours; and 2) nifedipine every 6 hours significantly reduced blood pressure throughout the 24 hours, without postural hypotension. Side effect were short-lasting (headache in five patients, palpitation without arrhythmias in eight patients, burning sensation in the face and legs in five patients and sporadic extrasystoles in five patients) and tended to disappear with continued treatment. Development of drug resistance, sodium retention, plasma volume expansion, renin release or angina pectoris were not observed during the study. Although these findings seem to differentiate nifedipine from other vasodilators currently used in the treatment of hypertension, broader experience and more prolonged trials with nifedipine as an antihypertensive agent will be needed before conclusions can be drawn on these particular aspects.

Haemodynamic effects of a calcium antagonistic agent (nifedipine) in hypertension: therapeutic implications.

1. In 27 severe primary hypertensive patients nifedipine (10 mg), administered orally, induced prompt (-21% of control at 30 min) and persistent (-17% at 120 min) fall of mean arterial pressure mediated through reduction of peripheral vascular resistance with rise of cardiac output. 2. The sublingual route (nine cases) showed more rapid onset of action and equal antihypertensive effectiveness. 3. In five patients with hypertensive crisis and acute left ventricular failure, the drug strikingly reduced systemic and pulmonary arterial pressures and relieved pulmonary oedema. 4. Prompt efficacy, ease of administration, absence of important side effects indicate that nifedipine may be a useful therapeutic agent in severe hypertension and in critical conditions that require rapid lowering of blood pressure.