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.