Effect of isradipine on cardiopulmonary baroreflex function, regional blood flow, and vascular responsiveness in hypertensive patients.
Calcium channel antagonists, when used to treat hypertension, may modulate baroreflex function and vascular responsiveness to endogenous vasoconstrictors. We studied regional blood flow, cardiopulmonary baroreflex function, and pressor responses in nine hypertensive patients (mean age of 44 +/- 7 years), eight males and one female, treated with isradipine (ISR), a dihydropyridine calcium channel antagonist, in a placebo-controlled, crossover trial. Each patient underwent determination of blood pressure and forearm, splanchnic, and renal blood flows (by strain gauge plethysmography and indocyanine green and p-aminohippurate clearances, respectively) at baseline and during cardiopulmonary unloading by lower body negative pressure (LBNP) at -10 and -20 mm Hg. ISR decreased the mean arterial pressure from 105 +/- 2 to 93 +/- 2 mm Hg (p less than 0.01). ISR did not change supine forearm or splanchnic vascular resistances, but renal vascular resistance fell 30% during treatment (from 0.12 +/- 0.02 to 0.09 +/- 0.01 mm Hg min/ml, p less than 0.05). Cardiopulmonary baroreceptor unloading by LBNP elicited comparable effects on forearm, splanchnic, and renal vascular resistance before and during ISR treatment. Baroreceptor unloading during placebo did not change plasma NE or PRA; during ISR, LBNP elicited a progressive rise in these hormones. The pressor response to NE was potentiated during ISR treatment (p less than 0.05); in contrast, the pressor response to angiotensin II infusion was blunted by calcium blockade (p less than 0.05). The present study, therefore, demonstrates that calcium channel blockade with ISR preserves, and may even augment, cardiopulmonary baroreflex function. These physiologic responses may contribute to the relatively low incidence of symptomatic orthostatic hypotension observed during chronic treatment with this agent.
Hirsch
A T
AT
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115.
Dzau
V J
VJ
Cutler
S S
SS
Levenson
D J
DJ
Creager
M A
MA
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D017275:Isradipine; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D000804:Angiotensin II; D009638:Norepinephrine; D017275:Isradipine