Sympathoexcitatory responses to the acute blood pressure fall induced by central or peripheral antihypertensive drugs.
This study was designed to evaluate the effects of an acute blood pressure reduction brought about by a peripheral vasodilator agent (prazosin) or by a drug combining central and peripheral modes of action (urapidil), on three markers of adrenergic tone such as muscle sympathetic nerve traffic (MSNA), venous plasma norepinephrine (NE), and heart rate (HR). In 12 untreated essential hypertensives (age, 50.7 +/- 1.9 years; mean +/- SEM), we evaluated in two experimental sessions, according to a double-blind crossover design, the effects of acute oral administration of 2 mg prazosin or 30 mg urapidil on beat-to-beat finger blood pressure (Finapres), HR (electrocardiogram), NE (high-performance liquid chromatography), and MSNA (microneurography at a peroneal nerve). In each session measurements were performed in the no-drug control state and repeated throughout a 3-h period after drug administration. For similar blood pressure reductions, the two drugs caused similar increases in NE and MSNA (peak effects: NE = +1.1 +/- 0.2 vs 0.9 +/- 0.2 nmol/L and MSNA = +10.9 +/- 1.8 vs +10.1 +/- 1.6 bursts/min for prazosin and urapidil respectively, P = ns between drugs), whereas HR increased more markedly after prazosin administration (+6.1 +/- 1.1 vs +2.4 +/- 0.8 beats/min, P < 0.05). These data provide evidence that acute blood pressure reductions induced by antihypertensive drugs with central or peripheral modes of action activate the sympathetic nervous system to a similar extent. Thus adrenergic activation is not peculiar to vasodilators but rather generalized to any drug-induced acute blood pressure fall, presumably because of the lack of a baroreflex resetting, which occurs during chronic but not during acute antihypertensive treatment.
Grassi
G
G
Cattedra di Medicina Interna I, Università di Milano, Ospedale S. Gerardo dei Tintori, Monza, Italy.
Seravalle
G
G
Stella
M L
ML
Turri
C
C
Zanchetti
A
A
Mancia
G
G
D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation; D009638:Norepinephrine / Q000097:blood; D010879:Piperazines / Q000097:blood / Q000494:pharmacology*; D011224:Prazosin / Q000097:blood / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013565:Sympatholytics / Q000097:blood / Q000494:pharmacology*
D000959:Antihypertensive Agents; D010879:Piperazines; D013565:Sympatholytics; C015568:urapidil; D009638:Norepinephrine; D011224:Prazosin