(Hypertension. 1999;34:39-43.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
From the Second Department of Physiology, Kagawa Medical University (Japan).
Correspondence to Hiroaki Kosaka, MD, PhD, Second Department of Physiology, Kagawa Medical School, 1750-1, Ikenobe, Miki-cho, Kita, Kagawa 761-0793, Japan. E-mail hkosaka{at}kms.ac.jp
AbstractThe present study is designed to investigate whether acetylcholine (ACh) elicits an endothelium-derived contracting factor (EDCF) and whether it contributes to decreased relaxant response induced by ACh in Dahl rats. Dahl salt-sensitive (DS) and -resistant (DR) rats were fed a 0.4% NaCl or an 8% NaCl diet for 4 weeks. High sodium intake significantly increased blood pressure in DS rats but not in DR rats. The carotid rings were suspended for isometric tension recording. ACh caused an endothelium-dependent contraction in carotid rings from hypertensive DS rats but not from normotensive Dahl rats. Atropine, indomethacin, SQ29548, or ONO-3708 (prostaglandin H2 [PGH2]/thromboxane A2 [TXA2] receptor antagonist) abolished ACh-induced contraction, and OKY-046 (inhibitor of TXA2 synthetase) partially attenuated the contraction. High sodium intake significantly enhanced contraction evoked by U46619, a PGH2/TXA2 receptor agonist, in both DS and DR rats. In contrast, ACh-induced relaxation was significantly depressed in the rings from hypertensive DS rats, and ONO-3708 partially improved the depressed relaxation. Administration of ONO-8809 (an orally active PGH2/TXA2 receptor antagonist; 30 µg per body per day) for 4 weeks neither reduced blood pressure nor improved the depressed ACh-induced relaxation in hypertensive DS rats. These results suggest that ACh causes release of EDCF in carotid rings of hypertensive DS rats, which is likely to be PGH2 and TXA2. The EDCF contributed in part to the depressed ACh-induced relaxation.
Key Words: acetylcholine arteries rats, Dahl endothelium-derived relaxing factor hypertension, sodium dependent receptors prostaglandin thromboxane
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