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 mediated 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 precontracted with 40 mmol/L KCl, in a concentration-related manner. Similarly, sufentanil and alfentanil relaxed rings, in the presence or absence of endothelium, which had been precontracted with phenylephrine. 3. Naloxone (10(-4) mol/L) had no significant effect on the relaxation induced by either sufentanil or alfentanil. 4. In a similar manner as phentolamine, pretreatment with sufentanil protected alpha-adrenoceptors from blockade by phenoxybenzamine (PBZ) in both endothelium intact and denuded rings, but the estimated potency of sufentanil was approximately 100-fold less than that of phentolamine in alpha-adrenoceptor protection. Treatment with alfentanil did not produce any receptor protection. 5. We concluded that, in the rat aorta, vascular relaxation induced by sufentanil is mediated by both alpha-adrenoceptor blockade and a direct effect on smooth muscle, whilst the relaxant effect of alfentanil is caused by direct effects alone. We also concluded that the endothelium has little role in relaxation produced by either drug.
Karasawa
F
F
Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Iwanov
V
V
Moulds
R F
RF
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D015760:Alfentanil / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017409:Sufentanil / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D015760:Alfentanil; D010656:Phenylephrine; D009270:Naloxone; D011189:Potassium Chloride; D017409:Sufentanil