Chronic hypotensive effects of verapamil in angiotensin hypertension are steroid independent.

This study was designed to examine the mechanisms that contribute to the chronic hypotensive effects of verapamil during angiotensin II-induced hypertension. Hypertension was induced in five dogs by continuous intravenous infusion of angiotensin II (5 ng/kg/min) for 17 days. On the sixth day of angiotensin II infusion when daily sodium balance was achieved, mean arterial pressure (control, 92 +/- 4 mm Hg), plasma aldosterone concentration (control, 5.2 +/- 0.9 ng/dl), and renal resistance (control, 0.28 +/- 0.01 mm Hg/ml/min) were increased 37 +/- 8 mm Hg, 13.6 +/- 5.0 ng/dl, and 0.20 +/- 0.05 mm Hg/ml/min, respectively. At this time there were no significant changes in glomerular filtration rate, effective renal plasma flow, net sodium and water balance, or extracellular fluid volume. Subsequently, when verapamil was infused (at 2 micrograms/kg/min) simultaneously with angiotensin II (days 7-13), there was a net loss of 55 +/- 10 meq sodium, a 7.0 +/- 0.7% fall in extracellular fluid volume, and approximately a 70% reduction in the chronic effects of angiotensin II on mean arterial pressure and renal resistance; in contrast, verapamil failed to attenuate the long-term aldosterone response to angiotensin II. Further, although glomerular filtration rate and effective renal plasma flow tended to increase during verapamil administration, there were no consistent chronic long-term changes in these renal indexes. In comparison with these responses in hypertensive dogs, when verapamil was infused for 7 days before the induction of angiotensin II hypertension, there were no significant changes in any measurements except mean arterial pressure, which fell 11 +/- 1 mm Hg. Thus, these data fail to support the hypothesis that the chronic stimulatory actions of angiotensin II on aldosterone secretion are dependent on a sustained increase in transmembranal calcium influx. Moreover, these data indicate that the pronounced long-term hypotensive effects of verapamil in angiotensin II hypertension are due to impairment of the direct renal actions of angiotensin II rather than the indirect sodium-retaining effects that are mediated via aldosterone secretion.