SUFENTANIL AND ALFENTANIL CAUSE VASORELAXATION BY MECHANISMS INDEPENDENT OF THE ENDOTHELIUM

1. The aim of these experiments was to determine if the vasorelaxation of the rat isolated aorta induced by sufentanil or alfentanil is medi ated by the endothelium, and, if not, by alpha-adrenoceptor blockade, or a direct effect on the smooth muscle. 2. Both sufentanil (from 10(- 7) mol/L to 10(-4) mol/L) and alfentanil (from 10(-7) mol/L to 3 x 10( -4) mol/L) relaxed rings, where endothelium was intact and precontract ed with 40 mmol/L KCl, in a concentration-related manner. Similarly, s ufentanil and alfentanil relaxed rings, in the presence or absence of endothelium, which had been precontracted with phenylephrine. 3. Nalox one (10(-4) mol/L) had no significant effect on the relaxation induced by either sufentanil or alfentanil. 4. In a similar manner as phentol amine, pretreatment with sufentanil protected alpha-adrenoceptors from blockade by phenoxybenzamine (PBZ) in both endothelium intact and den uded rings, but the estimated potency of sufentanil was approximately 100-fold less than that of phentolamine in alpha-adrenoceptor protecti on. Treatment with alfentanil did not produce any receptor protection. 5. We concluded that, in the rat aorta, vascular relaxation induced b y sufentanil is mediated by both a-adrenoceptor blockade and a direct effect on smooth muscle, whilst the relaxant effect of alfentanil is c aused by direct effects alone. We also concluded that the endothelium has little role in relaxation produced by either drug.