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VASORELAXATION OF RAT THORACIC AORTA CAUSED BY 14‐DEOXYANDROGRAPHOLIDE
Author(s) -
Zhang CY,
Tan BKH
Publication year - 1998
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1998.tb02226.x
Subject(s) - glibenclamide , phenylephrine , chemistry , verapamil , aorta , nitric oxide synthase , soluble guanylyl cyclase , caffeine , nitric oxide , thoracic aorta , vasodilation , endocrinology , methylene blue , medicine , pharmacology , channel blocker , receptor , guanylate cyclase , biochemistry , calcium , organic chemistry , photocatalysis , diabetes mellitus , blood pressure , catalysis
SUMMARY 1. The pharmacological effects of 14‐deoxyandrographolide on rat isolated thoracic aorta were examined. 2. 14‐Deoxyandrographolide (2.5‐120 μmiol/L) inhibited contractions induced by phenylephrine (PE; 0.1 μmol/L) and high K + (80mmol/L) in a concentration‐dependent manner in endothelium‐intact aorta. The effect was attenuated in endo‐thelium‐denuded aorta without modifying the maximal response. Like verapamil, 14‐deoxyandrographolide produced a much greater vasorelaxant effect in aorta precontracted by KCI than by PE. 14‐Deoxyandrographolide (20‐60 μmol/L) also inhibited responses of the rat aorta to PE. 3. In Ca 2+ ‐free medium (KCI 55mmol/L), 14‐deoxyandrographolide (20‐80 μmol/L) antagonized Ca 2+ ‐induced vasocon‐traction in a concentration‐dependent manner and transient contractions induced by both caffeine (10mmol/L) and noradrenaline (1μmol/L) were suppressed or almost abolished by 14‐deoxyandrographolide. 4. The vasorelaxant effect of 14‐deoxyandrographolide was partially antagonized by N G ‐nitro‐L ‐arginine methyl ester (25 μmol/L), a specific and competitive nitric oxide synthase (NOS) inhibitor, and methylene blue (10 μmol/L), a soluble guanylate cyclase inhibitor, but was not affected by indomethacin (20 μmol/L), a cyclo‐oxygenase inhibitor, or glibenclamide (10 μmol/L), an ATP‐sensitive K + ‐channel blocker. 5. These results suggest that the vasorelaxant activity of 14‐deoxyandrographolide may be mediated via the activation of NOS and guanylate cyclase, as well as the blockade of Ca 2+ influx through both voltage‐ and receptor‐operated Ca 2+ channels.