This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kadokami, T. Articles by Takeshita, A. Search for Related Content PubMed PubMed Citation Articles by Kadokami, T. Articles by Takeshita, A.

(Circulation. 1996;94:182-189.)
© 1996 American Heart Association, Inc.

Articles

Altered Serotonin Receptor Subtypes Mediate Coronary Microvascular Hyperreactivityin Pigs With Chronic Inhibitionof Nitric Oxide Synthesis

Toshiaki Kadokami, MD; Kensuke Egashira, MD; Kouichi Kuwata, MD; Yoshihiro Fukumoto, MD; Toshiyuki Kozai, MD; Hiroshi Yasutake, MS; Takeshi Kuga, MD; Hiroaki Shimokawa, MD; Katsuo Sueishi, MD; Akira Takeshita, MD

the Research Institute of Angiocardiology and Cardiovascular Clinic and the First Department of Pathology (K.S.), Kyushu University School of Medicine, Fukuoka, Japan.

Correspondence to Kensuke Egashira, MD, PhD, the Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-82, Japan.

Background We previously reported that chronic inhibition of nitric oxide synthesis by administration of N-nitro-L-arginine methyl ester (L-NAME) causes microvascular hyperreactivity to 5-hydroxytryptamine (5-HT) and vascular structural changes in pigs in vivo. In the present study, we investigated the relative contributions of 5-HT receptor subtypes to microvascular hyperreactivity in this animal model.

Methods and Results Coronary vasomotor response was studied in 16 pigs treated with oral L-NAME for 4 weeks (L group) and in 11 control pigs (C group). Intracoronary administration of 5-HT at 30 µg/kg decreased coronary blood flow (CBF) in the two groups. The decrease in CBF by 5-HT was greater (P<.01) in the L group than in the C group. The decrease in CBF by 5-HT in the C group was blocked completely by pretreatment with ketanserin, a 5-HT₂ antagonist. In contrast, the augmented decrease in CBF by 5-HT in the L group was only partly inhibited by ketanserin alone and was blocked completely by ketanserin and methiothepin, a 5-HT₁/5-HT₂ antagonist. The decrease in CBF caused by prostaglandin F₂ and the increase in CBF caused by nitroglycerin were comparable between the two groups and were not affected by the 5-HT antagonists.

Conclusions These results suggest that the 5-HT–induced microvascular hyperreactivity may be mediated by relative changes in affinity for 5-HT receptors or de novo expression of 5-HT₁ receptors in microvascular smooth muscle cells in our animal model.

Key Words: circulation • microcirculation • serotonin • endothelium-derived factors

This article has been cited by other articles:

				D. J. Duncker and R. J. Bache Regulation of Coronary Blood Flow During Exercise Physiol Rev, July 1, 2008; 88(3): 1009 - 1086. [Abstract] [Full Text] [PDF]

				S.-i. Saitoh, F. Onogi, K. Aikawa, M. Muto, T. Saito, K. Maehara, and Y. Maruyama Multiple endothelial injury in epicardial coronary artery induces downstream microvascular spasm as well as remodeling partly via thromboxane A2 J. Am. Coll. Cardiol., January 1, 2001; 37(1): 308 - 315. [Abstract] [Full Text] [PDF]

				V. Jain, Y. P. Vedernikov, G. R. Saade, K. Chawlisz, and R. E. Garfield Relaxation Kinetics of the Aorta in N{omega}-nitro-L-arginine Methyl Ester-Treated Pregnant Rats Reproductive Sciences, January 1, 1999; 6(1): 11 - 16. [Abstract] [PDF]

				M. Usui, T. Ichiki, M. Katoh, K. Egashira, and A. Takeshita Regulation of Angiotensin II Receptor Expression by Nitric Oxide in Rat Adrenal Gland Hypertension, September 1, 1998; 32(3): 527 - 533. [Abstract] [Full Text] [PDF]

				M. Takemoto, K. Egashira, H. Tomita, M. Usui, H. Okamoto, A. Kitabatake, H. Shimokawa, K. Sueishi, and A. Takeshita Chronic Angiotensin-Converting Enzyme Inhibition and Angiotensin II Type 1 Receptor Blockade : Effects on Cardiovascular Remodeling in Rats Induced by the Long-term Blockade of Nitric Oxide Synthesis Hypertension, December 1, 1997; 30(6): 1621 - 1627. [Abstract] [Full Text]