Diazepam attenuates phenylephrine-induced contractions in rat aorta.
In this in vitro study we examined the effects of diazepam on a phenylephrine-induced contraction in rat aorta and determined the associated cellular mechanism focusing on the endothelium-derived vasodilators. The concentration-response curves for phenylephrine and potassium chloride were generated in the presence or absence of diazepam. Phenylephrine concentration-response curves were generated from the endothelium-intact rings pretreated independently with N(W)-nitro-L-arginine methyl ester, PK 11195, tetraethylammonium, and indomethacin in the presence or absence of diazepam. Diazepam (7 x 10(-7) M) attenuated the phenylephrine-induced contraction in the endothelium-intact rings, whereas a large dose (5 x 10(-6) M) of diazepam attenuated the phenylephrine-induced contraction in the aortic rings with or without the endothelium. A pretreatment with the N(W)-nitro-L-arginine methyl ester completely abolished the diazepam (7 x 10(-7) M)-induced attenuation of the phenylephrine concentration-response curve, as well as the diazepam (5 x 10(-6) M)-induced attenuation of the maximal contractile response to phenylephrine. The N(W)-nitro-L-arginine methyl ester (10(-4) M)-induced contraction was enhanced in the rings pretreated with diazepam (5 x 10(-6) M). These results indicate that a supraclinical concentration of diazepam attenuates phenylephrine-induced contraction by increasing endothelial nitric oxide activity and directly affecting vascular smooth muscle.
Department of Anesthesiology and Pain Medicine, Ulsan University College of Medicine, Ulsan, Republic of Korea.
Soon-Eun
SE
Park
Ju-Tae
JT
Sohn
Cheol
C
Kim
Ki Churl
KC
Chang
Il-Woo
IW
Shin
Kyeong-Eon
KE
Park
Heon-Keun
HK
Lee
Young-Kyun
YK
Chung
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D010656:Phenylephrine; D003975:Diazepam