Effects of Urapidil on the Mechanical Properties of the Arterial Wall in Hypertension

Abstract

The effects of urapidil, a phenylpiperazine substituted derivative of uracil with selective alpha 1-adrenoceptor antagonist properties, on the mechanical properties of the arterial wall in hypertensive rats and male patients were studied. 15 twelve-week-old spontaneously hypertensive rats (SHR) were compared with 15 matched normotensive control Wistar Kyoto rats (WKY), in order to study carotid compliance in opened-chest anaesthetised animals. Carotid compliance was determined from the arterial volume-pressure relationship under control conditions, and after treatment with urapidil. Carotid compliance increased markedly (+31%; p less than 0.01) in WKY after incubation in situ with urapidil at doses corresponding to 0.5 and 1 mg/kg but it did not change significantly in SHR. Incubation with urapidil 2 mg/kg was necessary to induce a marked increase (+38%) in carotid compliance in SHR. In 12 male patients with hypertension who received intravenous urapidil 250 micrograms/kg infused as a single dose, pulse wave velocity decreased slightly (p less than 0.02) but no significant changes occurred in diameter and compliance. The study showed that urapidil influences arterial smooth muscle tone in rats and male patients, with resulting changes in arterial compliance; these changes are more substantial in animals than in humans.