Elevation of sympathetic activity by eprosartan in young male subjects.
BACKGROUND
Selective blockade of the type 1 angiotensin II receptors (AT1 receptors) reduced blood pressure (BP) elevation caused by sympathetic stimulation in the pithed rat model. This has been attributed to blockade of AT1 receptors located presynaptically on sympathetic nerve endings normally facilitating norepinephrine release. We examined the effects of AT1 receptor blockade on the sympathetic nervous system in humans.


METHODS
Twenty-nine young white men with normal to mildly hypertensive BP values participated in a double-blind, placebo-controlled, randomized cross-over protocol receiving 600 mg/d of eprosartan or placebo for 1 week. At the last day of intake we measured hemodynamic parameters, muscle sympathetic nerve activity by microneurography, and plasma levels of norepinephrine, epinephrine, and angiotensin II during rest and cardiovascular stress.


RESULTS
Eprosartan lowered resting mean arterial pressure (73.6 +/- 11.0 v 78.0 +/- 10.3 mm Hg, P <.05; Finapres, Ohmeda, Englewood, CO), and elevated heart rate (64.4 +/- 7.6 v 61.1 +/- 6.8 beats/min, P =.01), muscle sympathetic nerve activity (14.1 +/- 10.4 v 9.8 +/- 6.3 bursts/min, P <.05) and plasma angiotensin II (37.0 +/- 33.7 v 6.9 +/- 2.8 ng/L, P <.01), as well as norepinephrine levels (234.2 +/- 87.6 v 187.8 +/- 59.3 ng/L, P <.01). Eprosartan did not blunt sympathetic activation caused by lower body negative pressure or mental stress.


CONCLUSIONS
These results contrast with animal data showing antiadrenergic properties of this drug. If any, it appeared, that eprosartan causes augmented central neural vasoconstrictor outflow paralleled by increased plasma levels of norepinephrine, which casts doubt on its ability to dampen norepinephrine release from peripheral sympathetic nerve endings in humans. We hypothesize that eprosartan leads to a resetting of the baroreflex, presumably by the markedly elevated circulating angiotensin II.
Heusser
Karsten
K
Department of Medicine IV/Nephrology, University of Erlangen-Nuremberg, Krankenhausstrasse 12, 91054 Erlangen, Germany. karsten.heusser@gmx.de
Vitkovsky
Jan
J
Raasch
Walter
W
Schmieder
Roland E
RE
Schobel
Hans P
HP
D000179:Acrylates / Q000494:pharmacology*; D000328:Adult; D000804:Angiotensin II / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004562:Electrocardiography; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008150:Lower Body Negative Pressure; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology; D009638:Norepinephrine / Q000097:blood; D011446:Prospective Studies; D013315:Stress, Psychological / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013876:Thiophenes
D000179:Acrylates; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002395:Catecholamines; D007093:Imidazoles; D013876:Thiophenes; D000804:Angiotensin II; C068373:eprosartan; D009638:Norepinephrine