Long-term renal and systemic effects of calcium entry blockers in normotensive and experimental hypertensive dogs

Abstract

The effect of diltiazem administered as a sustained infusion (10 to 15 μg/kg/min) was studied in 3 groups of conscious instrumented dogs: 4 normotensive, 5 Goldblatt hypertensive (GH) and 4 deoxycorticosterone acetate-salt treated Goldblatt hypertensive (DSGH) dogs. Mean arterial blood pressure, left renal blood flow and heart rate were monitored, and the plasma renin activity was determined in a control session and after 3 to 5 days of diltiazem infusion in the normotensive and after 5 to 8 days of infusion in the 2 hypertensive groups. Pressor and renal blood flow responses to phenylephrine, norepinephrine and angiotensin II were also determined in the control session and on the last day of the diltiazem infusion. Mean arterial blood pressure was found to be decreased at the 5 to 8-day interval in the DSGHs and in the GHs, but the change in the latter group was not statistically significant. Mean arterial blood pressure was unchanged in the normotensives. Renal vascular resistance was decreased by diltiazem in the normotensive group at 3 to 5 days and in the DSGHs at 1 to 2 days. Heart rate was not significantly affected by diltiazem in the hypertensive groups, but was increased in the normotensive group at the 1 to 2-day interval. Plasma renin activity tended to increase in the hypertensive, but not in the normotensive dogs. Pressor and renal blood flow responses to all the agonist agents tested were decreased in the presence of diltiazem. The hypotensive effect of diltiazem was more prominent in the conscious DSGHs than in the normotensive dogs or GHs; a decrease in renal vascular resistance was seen in both the normotensive and DSGH groups. Hypotension in these animals may be related at least in part to depression of vasoconstrictor stimuli.