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

Abstract

SUMMARY Calcium entry blockers are potent vasodilators and may be suitable for antihypertensive therapy. We investigated hemodynamic responses together with changes of plasma catecholamines 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 m 2 , 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 • m 2 ), a pattern suggestive of resetting of baroreflexes. Forearm hemodynamic changes paralleled the systemic circulation 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, respectively). 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. ( 1 Calcium entry blockers which decrease the intracellular free calcium concentration mainly by a reduction of the transmembranous calcium influx into muscle cells 2 and thereby reduce

Haemodynamic profile of the potassium channel activator EMD 52692 in anaesthetized pigs

“…The finding that with the intravenous infusions the increase in flow was almost exclusively confined to the subepicardial layers is not surprising in view of the tachycardia and hypotension (Domenech & Goich, 1976); this has also been demonstrated for nicorandil (Verdouw et al, 1987). Chronic treatment often leads to a reduction of the reflex tachycardia (Kiowski et al, 1983). If the coronary vasodilator action were to be sustained with chronic treatment, the lower heart rate would most likely not only lower myocardial 02-demand but also shift coronary blood flow in favour of the subendocardial layers.…”

The effects of acute and chronic dihydropyridine calcium antagonist therapy on baroreflex sensitivity: a re-analysis using the sequence method

“…The literature is conflicting on the question of persisting sympathetic hyperactivity following calcium antagonism, but the majority of reports suggest that hyperactivity does persist even with the long acting preparations. 5,9,[18][19][20][21] Recently, it has been shown that peripheral muscle sympathetic activity as recorded by microneurography was increased over baseline after 4 weeks treatment with amlodipine. 21 It has been suggested that one reason for the persisting sympathetic activity with short acting calcium antagonists relates to the profile of induced blood pressure reduction with formulations which cause rapid falls in blood pressure and doses or dosing intervals which result in substantial peak:trough ratios, thus causing increases in sympathetic activity in the initial hours after dosage.…”

Nifedipine increases and glyceryl trinitrate decreases apparent liver blood flow in normal subjects.

“…This indirect method is based on the assumption that the drugs under study do not alter the hepatic extraction ratio of ICG and in the case of glyceryl trinitrate there is no evidence that this occurs in cirrhotic patients (Groszmann et al, 1982). Studies were performed in random order and separated by at least 3 days, as control, 5 min following glyceryl trinitrate (500 ,ug sublingually) and 30 min following nifedipine (10 mg sublingually) at which time these drugs produce their maximum effects (Maclean & Feely, 1983;Kiowski et al, 1983 Figure 1 Effect of glyceryl trinitrate (500 ,ug) and nifedipine (10 mg) on apparent liver blood flow in six subjects.…”