On the mechanism of the hypotensive action of urapidil.
The cardiovascular effects of urapidil have been investigated in the anaesthetized rat and cat. Intravenous (i.v.) urapidil produced a significant hypotension without change in heart rate. Directly injected into the brain cavities, urapidil produced a hypotensive effect only at very high doses (1 mg/kg) in normotensive and spontaneously hypertensive rats. In cats, however, intracisternal (i.c.) injection of urapidil produced hypotension at doses of 30 and 100 micrograms/kg. In this species, a central component to the hypotensive effect of the drug is therefore possible. However, urapidil antagonized competitively the contraction of the rat aorta induced by noradrenaline. The drug has alpha-adrenoceptor blocking properties, which probably mainly explain its hypotensive action. On the other hand, urapidil induced a presynaptic inhibition in the heart, which may explain the lack of heart rate changes during the hypotensive effect of the drug. Urapidil may therefore stimulate presynaptic alpha 2-adrenoceptors in the heart as well as in the vas deferens.
Bousquet
P
P
Institut de Pharmacologie, Faculté de Médecine, Strasbourg, France.
Feldman
J
J
Schwartz
J
J
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002415:Cats; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D010879:Piperazines; C015568:urapidil