Abstract
This in vitro study was designed to assess the effects of fentanyl on isolated rabbit thoracic aorta rings contracted with phenylephrine. Methods included contraction of aorta rings with phenylephrine (10–5 M) and recording the changes after increasing concentrations of fentanyl (10–9 M – 10–5 M). Similar experiments were done after incubation with Nω- nitro-L-arginine methyl ester (10–4 M), indomethacin (10-5 M), naloxone (10–5 M), ouabain (10–5 M), TEA (10–4 M) and glibenclamide (10–5 M). It was revealed that, fentanyl causes relaxation in rabbit aorta rings precontracted with phenylephrine. Removal of endothelium significantly reduces the relaxant response to fentanyl. Nitric oxide synthase inhibitor L-NAME, K+ channel blocker glibenclamide and Na+/K+ ATPase inhibitor ouabain inhibits the relaxant effect of fentanyl in endothelium intact aorta rings. These results suggest that fentanyl causes dose dependent vasodilatation in the rabbit aorta via activation of KATP channels and Na+-K+ -ATPase, and nitric oxide released from endothelium.
Highlights
Fentanyl is a synthetic opioid which is commonly used for cardiac and vascular anesthesia in very high doses 1, 2
These results suggest that fentanyl causes dose dependent vasodilatation in the rabbit aorta via activation of KATP channels and Na+-K+ -ATPase, and nitric oxide released from endothelium
Protocol 2: to determine whether the vasorelaxant effect of fentanyl is mediated by nitric oxide (NO) or prostanoids, endothelium intact aorta strips precontracted with phenylephrine (10–5 M) were incubated for 20 minutes with a NO synthase inhibitor, Nω-nitro-L-arginine methyl ester (l-NAME) (10–4 M) (n = 8) and a cyclooxygenase inhibitor, indomethacin (10–5M) (n = 8) After this incubation, concentration-response curves were obtained to cumulative doses of fentanyl (10–9 M – 10–5 M)
Summary
Fentanyl is a synthetic opioid which is commonly used for cardiac and vascular anesthesia in very high doses 1, 2. Opioids can have marked effects upon the circulation in animals, and these effects can be mediated by either alteration in autonomic nervous system activity or by direct actions on blood vessels 1. Studies regarding the effects of fentanyl on different vascular structures, and the mechanisms involved in these actions revealed conflicting results 3-5. It would appear that different mechanisms might be involved in fentanyl’s vascular effects, depending on the species and the blood vessel. To best of our knowledge, the effect of fentanyl on rabbit aorta has not been studied. This in vitro study was designed to assess the effects and the possible mechanisms of these effects of fentanyl on isolated rabbit thoracic aorta rings contracted with phenylephrine
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