Cardiovascular and metabolic profile during intervention with urapidil in humans.

Abstract

Increased sympathetic activity or vascular reactivity to norepinephrine or both may play a complementary role in the pathogenesis of essential hypertension. Therefore, blood pressure regulation and metabolic correlates of cardiovascular risk were evaluated in 19 normal subjects and in 13 subjects with essential hypertension receiving placebo and after 4 weeks of intervention with urapidil, an agent that was found experimentally to exert a combined central sympathetic and peripheral .alpha.-adrenergic receptor inhibition. In hypertensive patients, urapidil normalized the initially low norepinephrine pressor dose (+ 106%), mildly increased basal plasma norepinephrine levels (+36%), and markedly shifted the plasma norepinephrine concentration-blood pressure response curve (p < 0.01). Blood pressure was decreased (p < 0.001). In normal subjects, urapidil produced only mild increases in norepinephrine plasma levels (+22%) and norepinephrine pressor dose (+ 38%) and no change in blood pressure. Body weight, exchangeable sodium, and blood volume were unaltered or increased slightly. Heart rate; plasma epinephrine, renin, angiotensin II, basal aldosterone, and electrolyte levels; plasma clearances of norepinephrine and angiotensin II; pressor effects of angiotensin II; chronotropic resposnes to isoproterenol or a norepinephrine-induced rise in blood pressure; and urinary prostaglandin F2.alpha. excretion, as well as serum lipoprotein fractions and glucose, insulin, and uric acid levels, were not significantly modified by urapidil. Prostaglandin E2 excretion tended to be increased. Aldosterone responsiveness to angiotensin II was increased by urapidil in normal (p < 0.05) but not in hypertensive subjects. These findings suggest that urapidil may decrease blood pressure in essential hypertension predominantly through peripheral .alpha.-adrenergic receptor inhibition by lowering an abnormally high vascular norepinephrine reactivity without causing an equivalent increase in adrenergic activity. No alteration in metabolic correlates of cardiovascular risk occurred. A physiological sympathetic inhibition of angiotensin II-stimulated aldosterone release may be mediated by an .alpha.-adrenergic receptor related mechanism that seems to be impaired in essential hypertension.