Effects of selective angiotensin II receptor blockade on sympathetic nerve activity in primary hypertensive subjects.
OBJECTIVE
The role of the renin-angiotensin system in the regulation of sympathetic nervous activity in human hypertension was evaluated in patients with moderate primary hypertension. For that purpose, the effects of selective angiotensin II (ANG II) receptor blockade by valsartan on sympathetic outflow to the muscle vascular bed and hemodynamic parameters were examined. Results were compared with the effects of the peripherally acting calcium antagonist amlodipine.


METHODS
Eighteen hypertensive but otherwise healthy subjects were examined in a double-blind, placebo-controlled, cross-over protocol receiving either valsartan or amlodipine or placebo for 7 days in a randomized sequence. Treatment periods were separated by washout periods of 2 weeks.


METHODS
At the seventh day of treatment, blood pressure, heart rate, muscle sympathetic nerve activity (MSNA), norepinephrine, renin and angiotensin were measured during resting conditions. Additionally, parameters were measured after administration of negative pressure of -15 mmHg to the lower part of the body and after a cold pressor test.


RESULTS
Both antihypertensive drugs significantly decreased oscillometrically measured systolic blood pressure and diastolic blood pressure without any difference in effect. While valsartan did not affect the heart rate at rest, amlodipine increased it significantly. Likewise, MSNA was significantly enhanced by amlodipine but not by valsartan. Only ANG II receptor blockade increased renin and angiotensin levels.


CONCLUSIONS
Selective ANG II receptor blockade not only decreases blood pressure, but also shifts the baroreflex set-point for the initiation of counter-regulatory reflex responses of heart rate and blood pressure towards normal blood pressure levels. Thus, data suggest that ANG II plays a pathogenetic role in the elevation of the baroreflex set point in primary hypertensive subjects.
Struck
Jan
J
Department of Internal Medicine I, and cInstitute of Pharmacology, Medical University of Lübeck, Lübeck, Germany.
Muck
Philip
P
Trübger
Daniel
D
Handrock
Renate
R
Weidinger
Gottfried
G
Dendorfer
Andreas
A
Dodt
Christoph
C
D017311:Amlodipine / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000294:innervation; D044140:Receptor, Angiotensin, Type 1; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000068756:Valsartan; D014665:Vasodilator Agents / Q000627:therapeutic use*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D014665:Vasodilator Agents; D017311:Amlodipine; D000068756:Valsartan; D014633:Valine