SUMMARY The long-term effects (3.5 months) of a new calcium entry blocker of the 1-4-dihydropyridine class, isradipine , on renal hemodynamics and excretional parameters were investigated in 10 essential hypertensive subjects (World Health Organization Classes I and II). Blood pressure and renal vascular resistance fell significantly (p < 0.001), and a slight increase in glomerular filtration rate and renal plasma flow was seen (p<0.05). Output of fluid from the proximal tubules, measured as clearance of lithium and uric acid, increased significantly (p<0.01 and p<0.05, respectively), and a compensatory increase in absolute reabsorption of sodium beyond the proximal tubular level accompanied by an increase in clearance of potassium was noted. A 40% increase in the resultant clearance of sodium (p<0.01) and an increase in diuresis (p<0.05) followed the morning dose of isradipine after 3.5 months of treatment. Changes in blood pressure were significantly correlated with changes in absolute proximal reabsorption of sodium (r = 0.81), excretion of sodium (r = -0.64), and diuresis (r = -0.80). Thus, the natriuretic properties of calcium entry blockers may be more important for the long-term antihypertensive effect than the vasodilator effect per se. A model for renal sodium handling following treatment with calcium entry blockers was proposed. Although a causal relationship is not implied, isradipine induced a sustained, repetitive postdose effect on proximal fluid output, net natriuresis, and diuresis, that was intimately related to the long-term blood pressureregulating response.

Summary. The acute effects of a single, 20 mg oral dose of nitrendipine were studied in 10 women at between 32 and 42 weeks gestation with stable pregnancy‐induced hypertension (PIH). Blood pressure (BP), maternal heart rate and fetal heart rate (FHR) were assessed for 8 h after nitrendipine intake together with the plasma levels of nitrendipine, noradrenaline, adrenaline, plasma renin activity (PRA) and vasopressin. The mean initial systolic/diastolic BP was 158 (SEM 3.7)/ 108 (SEM 2.7) mmHg. Within 1 h stable, reduced mean BP‐levels of 141–145/90–95 mmHg were reached and maintained for 4 h after medication. This antihypertensive effect was closely related to the maternal plasma concentration of nitrendipine, which reached a maximum of 9.1 (SEM 2.6) ng/ml 3 h after tablet intake. After 4 h, systolic and diastolic BPs slowly increased in parallel to a successive decrease in plasma concentrations of nitrendipine. Maternal heart rate increased by less than 10%, while FHR remained unchanged. No hypotensive incidents occurred. The initial mean plasma concentrations of noradrenaline, adrenaline, vasopressin and PRA did not change during the treatment. No major maternal and no fetal side‐effects were observed. Three of 10 patients experienced mild, transient facial flushing.

The effect of histamine (0.01–200 μM) was studied in isolated human pulmonary vessels. Histamine induced concentration dependent contractions in both arteries and veins. In veins the maximal response to histamine was lower than in arteries. Histamine and 2‐methyl‐histamine had a dual action in both arteries and veins clearly demonstrated in vessels precontracted with potassium. In these vessels histamine and 2‐methyl‐histamine induced relaxation at low concentrations and contractions at high concentrations. Veins were more sensitive to the relaxant effect of histamine than arteries. Mepyramine eliminated the dual action of 2‐methyl‐histamine and histamine and unveiled a mepyramine resistant relaxation at the highest histamine concentrations used which was resistant to the effect of cimetidine and metiamide. The H2 receptor agonist dimaprit (10–400 μM) induced a slight relaxation in both arteries and veins that could be eliminated by metiamide (100 μM). The results show that histamine has a dual action in human pulmonary vessels which includes a contractile effect mediated via H1 receptors and a relaxant response partly mediated through H1 receptors and partly via unspecific mechanisms. However, an H2 mediated relaxant effect cannot be excluded.

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