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Anesth Analg 2006;102:682-689
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000196521.62806.43

CARDIOVASCULAR ANESTHESIA

Diazepam Attenuates Phenylephrine-Induced Contractions in Rat Aorta

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

*Department of Anesthesiology and Pain Medicine, Ulsan University College of Medicine, Ulsan, Republic of Korea; {dagger}Department of Anesthesia and Pain Medicine, {ddagger}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 NW-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 NW-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 NW-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.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2006 by the International Anesthesia Research Society.