Calcium antagonism abolishes the antipressor action of vasopressin (V1) receptor antagonism.
Previous studies demonstrate that vasopressin (V1) receptor antagonism lowers arterial pressure in blacks. This action of V1 receptor blockade may be mediated through various mechanisms including changes in intracellular calcium fluxes. This study was undertaken to test the hypothesis that inhibition of calcium entry may attenuate the reduction in arterial pressure observed with V1 receptor blockade. Sixteen hypertensive patients, 8 whites and 8 blacks, were examined. Each had their antihypertensive therapy stopped for 1 week. Following three baseline blood pressure measurements, all patients were given an intravenous bolus injection of a V1 receptor antagonist. Blood pressure was monitored every 10 min for a period of 3 h. Subjects were then randomized to either 0.2 mg clonidine twice daily or 300 mg diltiazem CD daily for a period of 3 days and the previous experiments repeated. Patients were then crossed over to the other drug for an additional 3 days and the experiments repeated. There was a significant reduction from baseline in the mean arterial pressure among blacks but not whites (-11 +/- 3 delta mm Hg blacks versus -1 +/- 2 delta mm Hg whites, P < .01). In the presence of clonidine, there were similar reductions in arterial pressure in both groups (P = .026) with a further reduction following V1 receptor blockade only in the blacks (-7 +/- 3 delta mm Hg blacks versus 6 +/- 2 delta mm Hg whites; P < .001). Conversely, in the presence of diltiazem CD, there were no further reductions in arterial pressure in either group following the V1 receptor antagonist. We conclude that calcium channel blockade abolishes the blood pressure lowering response of V1 receptor blockade in blacks.
Bakris
G L
GL
Rush University Hypertension Center, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA.
Kusmirek
S L
SL
Smith
A C
AC
Gavras
I
I
Gavras
H
H
D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists; D000959:Antihypertensive Agents / Q000494:pharmacology*; D044383:Black People; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013564:Sympathetic Nervous System / Q000502:physiology; D044465:White People
D065092:Antidiuretic Hormone Receptor Antagonists; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers