We have assessed if fentanyl interacts with the endothelium to affect vessel tone. In the presence or absence of endothelium, fentanyl in concentrations greater than 10(-7) mol litre-1 decreased the sensitivity of the rat aortic rings to phenylephrine, but fentanyl in smaller concentrations had no significant effect. Rings, with or without endothelium, and pre-contracted by phenylephrine were relaxed by fentanyl, and this relaxation was not inhibited by the opioid receptor antagonist, naloxone. Pretreatment of the rings with either fentanyl or phentolamine protected alpha-adrenoceptors from block by the alpha-adrenoceptor antagonist, phenoxybenzamine. We conclude that, in the rat aorta, fentanyl-induced relaxation was mediated by alpha-adrenergic receptors, and that the endothelium modulated, but did not mediate, this relaxation.
Synergism between the contractile effects of platelet-derived serotonin (5HT) and thromboxane A2 (TXA2) on a human blood vessel has been investigated by incubating strips of digital arteries in subcontractile concentrations of either 5HT or the TXA2-mimetic agent U46619. Either agonist U46619 or 5HT, in subcontractile concentrations, significantly potentiated the contractile response to the other. The 5HT antagonist ketanserin (10 mumol/l), the Ca2+ antagonist drugs verapamil (3 mumol/l), or nifedipine (10 nmol/l), or a Ca2+-free bathing medium, reduced the contractile responses to 5HT, but had no effect on the potentiation mediated by U46619. The interaction between TXA2 and 5HT derived from platelets was studied by measuring responses to platelets 1 min after aggregation (in the absence or the presence of ketanserin 10 mumol/l), and 20 min after aggregation. The results indicated that the response to platelets mediated by TXA2 and 5HT was greater than the sum of those mediated by TXA2 or 5HT separately. It is concluded that synergism between the contractile effects of 5HT and U46619 occurs in human blood vessels; that this is mediated by enhanced utilization of intracellular, rather than extracellular calcium; and that synergism can also occur when 5HT and TXA2 are released from stimulated human platelets.
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.
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