Divergent effects of dihydropyridine and phenylalkylamine calcium channel antagonist classes on autonomic function in human hypertension.
Calcium channel antagonists differ by class in reported frequency of side effects that suggest reflex sympathoadrenal activation. Do such differences result from differential effects on autonomic and baroreflex function? The present study compared acute and chronic effects of two classes of calcium channel antagonists, the dihydropyridine type (felodipine) and the phenylalkylamine type (verapamil), on efferent sympathetic outflow and baroreflex slope in 15 essential hypertensive subjects. Blood pressure, heart rate, hemodynamics, and biochemistries were determined at baseline and after acute (first dose) and chronic (4 weeks) administration of the drugs versus placebo. Acutely, felodipine caused a greater decrease in blood pressure associated with a larger decline in systemic vascular resistance than the corresponding effects produced by verapamil. Chronically, there were similar, significant declines in blood pressure (P = .001) and systemic vascular resistance (P = .001) after each drug. Acutely, increased sympathetic activity after felodipine was suggested by reflex tachycardia (from 69 +/- 3 to 74 +/- 2 beats per minute, P = .014) and elevation of plasma norepinephrine (from 264 +/- 25 to 323 +/- 25 pg/mL, P = .037), whereas after verapamil the corresponding changes were closely similar to those after placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
Kailasam
M T
MT
Department of Medicine, University of California, San Diego 92161, USA.
Parmer
R J
RJ
Cervenka
J H
JH
Wu
R A
RA
Ziegler
M G
MG
Kennedy
B P
BP
Adegbile
I A
IA
O'Connor
D T
DT
D000450:Aldosterone / Q000097:blood; D000704:Analysis of Variance; D001341:Autonomic Nervous System / Q000187:drug effects*; D017704:Baroreflex / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002307:Cardiography, Impedance; D053379:Chromogranin A; D002864:Chromogranins / Q000097:blood; D004837:Epinephrine / Q000097:blood; D015736:Felodipine / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D012083:Renin / Q000097:blood; D013564:Sympathetic Nervous System / Q000187:drug effects; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D053379:Chromogranin A; D002864:Chromogranins; D000450:Aldosterone; D014700:Verapamil; D012083:Renin; D015736:Felodipine; D009638:Norepinephrine; D004837:Epinephrine