Hemodynamic and reflex responses to acute and chronic antihypertensive therapy with the calcium entry blocker nifedipine.

Calcium entry blockers are potent vasodilators and may be suitable for antihyperten-sive therapy. We investigated hemodynamic responses together with changes of plasma catechola-mines and renin activity (PRA) in 11 men (38.2 ± 5.1 years) with essential hypertension (EHT, WHO I-II) after administration of nifedipine 10 mg sublingually (s.l.) and after 6 weeks treatment with nifedipine 20 mg three times daily. Acutely, nifedipine 10 mg s.l. decreased intraarterial blood pressure (BP, 156.2 ± 5.3/83.1 ± 4.6 mm Hg) significantly after 15 minutes (p<0.05) averaging 147.3 ± 5.4/76.5 ± 4.5 mm Hg after 30 minutes (p<0.01) and 135.5 ± 4.4/69.7 ± 2.9 mm Hg after 6 weeks (p<0.01). Acutely increased heart rate and cardiac index (CI), plasma norepinephrine (PNE), and PRA as a consequence of baroreflex activation due to markedly reduced systemic vascular resistance index (SVRI, 39.3 ± 4.3 vs 30.3 ± 3.0 units m2, p<0.01). There was a direct correlation between acute changes of PNE and CI (r = 0.72, p < 0.05) suggesting an important role of acute sympathetic stimulation in the regulation of acute BP responses to nifedipine. Signs of sympathetic activation were absent at 6 weeks while SVRI decreased further (28.1 ± 1.5 units m2), a pattern suggestive of resetting of baroreflexes. Forearm hemodynamic changes paralleled the systemic circu-lation and blood volume did not change. Chronic changes in mean blood pressure and SVRI were significantly related to pretreatment values (r = 0.65 and r = 0.95, p < 0.05 and <0.01, respective-ly). Changes in blood pressure were inversely related to pretreatment PRA (r = − 0.71 and 0.67, p<0.05, acute and chronic effects, respectively). Our findings are compatible with the reduction by nifedipine of a calcium-dependent vasoconstrictor mechanism in EHT. The depressor response to nifedipine is acutely, but not chronically, counteracted by baroreflex activation, and its magnitude is inversely related to the activity of the renin-angiotensin system. The lack of volume retention or chronic sympathetic stimulation suggests the potential by nifedipine for effective antihypertensive monotherapy.