Inhibition of nitric oxide/cyclic GMP-mediated relaxation by purified flavonoids, baicalin and baicalein, in rat aortic rings.
The dried roots of Scutellaria baicalensis Georgi (Huangqin) are widely used in traditional Chinese medicine. We purified two flavonoids, baicalin and baicalein from S. baicalensis Georgi and examined their effects on isolated rat aortic rings. Baicalin (3-50 microM) inhibited endothelium/nitric oxide (NO)-dependent relaxation induced by acetylcholine (Ach) or cyclopiazonic acid (CPA). Baicalein at 50 microM abolished Ach-induced relaxation and markedly reduced CPA-induced relaxation. Treatment with 1mM L-arginine partially but significantly reversed the effects of baicalin (50 microM) or baicalein (50 microM) on Ach-induced relaxation. In endothelium-denuded rings, treatment with baicalin, baicalein or methylene blue partially inhibited relaxations induced by the NO donors, sodium nitroprusside (SNP) and hydroxylamine. Both flavonoids markedly reduced the increase in cyclic GMP levels stimulated by Ach in endothelium-intact rings and by SNP in endothelium-denuded rings. In contrast, exposure of endothelium-denuded rings to baicalin or baicalein did not affect relaxations induced by pinacidil or NS 1619, putative K+ channel activators. Neither flavonoids affected agonist-induced increase in the endothelial [Ca2+]i. Our results indicate that baicalin and baicalein attenuated NO-mediated aortic relaxation and cyclic GMP increases, likely through inhibition of NO-dependent guanylate cyclase activity.
Huang
Yu
Y
Department of Physiology, Chinese University of Hong Kong, Hong Kong, PR China. yu-huang@cuhk.edu.hk
Wong
Chi Ming
CM
Lau
Chi-Wai
CW
Yao
Xiaoqiang
X
Tsang
Suk Ying
SY
Su
Ya Lun
YL
Chen
Zhen Yu
ZY
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*
D000975:Antioxidants; D044950:Flavanones; D005419:Flavonoids; D009569:Nitric Oxide; C038044:baicalin; C006680:baicalein; D006152:Cyclic GMP; D002118:Calcium