Inhibitory effect of fentanyl on phenylephrine-induced contraction of the rat aorta.
OBJECTIVE
Fentanyl was reported to inhibit the alpha(1)-adrenoceptor agonist-induced contraction. The goal of this in vitro study was to identify the alpha(1)-adrenoceptor subtype primarily involved in the fentanyl-induced attenuation of phenylephrine-induced contraction in isolated endothelium-denuded rat aorta.


METHODS
Aortic rings were suspended in order to record isometric tension. Concentration-response curves for phenylephrine (10(-9) to 10(-5) M) were generated in the presence or absence of one of the following drugs: fentanyl (3 x 10(-7), 10(-6), 3 x10(-6) M), 5-methylurapidil (3 x10(-8), 10(-7), 3 x 10(-7) M), chloroethylclonidine (10(-5) M) and BMY 7378 (3 x 10(-9), 10(-8), 3 x 10(-8) M). Phenylephrine concentration-response curves were generated in the presence or absence of fentanyl in rings pretreated with either 3 x10(-9) M prazosin, 10(-9) M 5-methylurapidil or 3 x 10(-9) M BMY 7378.


RESULTS
Fentanyl (10(-6), 3 x 10(-6) M) attenuated phenylephrine-induced contraction in the rat aorta. 5-Methylurapidil and BMY 7378 produced a parallel rightward shift in the phenylephrine concentration-response curve. The pA(2) values for 5-methylurapidil and BMY 7378 were estimated to be 7.71 +/- 0.15 and 8.99 +/- 0.24, respectively. Fentanyl (10(-6) M) attenuated phenylephrine-induced contraction in rings pretreated with 10(-9) M 5-methylurapidil, but did not alter the rings when pretreated with 3 x 10(-9) M BMY 7378. Pretreatment of the rings with chloroethylclonidine showed a 72.9 +/- 2.3% reduction in phenylephrine-induced maximal contraction.


CONCLUSIONS
The results suggest that fentanyl attenuates phenylephrine-induced contraction by inhibiting the pathway involved in the alpha(1D)-adrenoceptor-mediated contraction of the rat aorta.
Park
Kyeong-Eon
KE
Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, 90 Chilam-dong, Jinju, Korea.
Sohn
Ju-Tae
JT
Jeong
Young Seok
YS
Sung
Hui-Jin
HJ
Shin
Il-Woo
IW
Lee
Heon-Keun
HK
Chung
Young-Kyun
YK
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D005283:Fentanyl / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D010656:Phenylephrine; C051731:chlorethylclonidine; C053428:BMY 7378; D003000:Clonidine; D005283:Fentanyl