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CARDIOVASCULAR ANESTHESIA

Diazepam Attenuates Phenylephrine-Induced Contractions in Rat Aorta

Soon-Eun Park, MD^*, Ju-Tae Sohn, MD, Cheol Kim, MD, Ki Churl Chang, PhD, Il-Woo Shin, MD, Kyeong-Eon Park, MD, Heon-Keun Lee, MD, and Young-Kyun Chung, MD

*Department of Anesthesiology and Pain Medicine, Ulsan University College of Medicine, Ulsan, Republic of Korea; Department of Anesthesia and Pain Medicine, Department of Pharmacology, Institutes of Health Sciences, Gyeongsang National University College of Medicine, Jinju, Gyeongnam, Republic of Korea

Address correspondence and reprint requests to Ju-Tae Sohn, MD, Department of Anesthesia and Pain Medicine, Gyeongsang National University Hospital, 90 Chilam-dong, Jinju, Gyeongnam, 660-702, Republic of Korea. Address e-mail to jtsohn{at}nongae.gsnu.ac.kr.

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.