cyclic-gmp and baicalin

Baicalin isolated from Scutellaria baicalensis is a traditional Chinese herbal medicine used for cardiovascular dysfunction. The ionic mechanism of the vasorelaxant effects of baicalin remains unclear. We investigated whether baicalin relaxes mesenteric arteries (MAs) via large-conductance Ca2+-activated K+ (BK(Ca)) channel activation and voltage-dependent Ca2+ channel (VDCC) inhibition. The contractility of MA was determined by dual wire myograph. BK(Ca) channels and VDCCs were measured using whole-cell recordings in single myocytes, enzymatically dispersed from rat MAs. Baicalin (10-100 microM) attenuated 80 mM KCl-contracted MA in a concentration-related manner. L-NAME (30 microM) and indomethacin (10 microM) little affected baicalin (100 microM)-induced vasorelaxations. Contractions induced by iberiotoxin (IbTX, 0.1 microM), Bay K8644 (0.1 microM) or PMA (10 microM) were abolished by baicalin 100 microM. In MA myocytes, baicalin (0.3-30 microM) enhanced BK(Ca) channel activity in a concentration-dependent manner. Increased BK(Ca) currents were abolished by IbTX (0.1 microM). Baicalin-mediated (30 microM) BK(Ca) current activation was significantly attenuated by an adenylate cyclase inhibitor (SQ 22536, 10 microM), a soluble guanylate cyclase inhibitor (ODQ, 10 microM), competitive antagonists of cAMP and cGMP (Rp-cAMP, 100 microM and Rp-cGMP, 100 microM), and cAMP- and cGMP-dependent protein kinase inhibitors (KT5720, 0.3 microM and KT5823, 0.3 microM). Perfusate with PMA (0.1 microM) abolished baicalin-enhanced BK(Ca) currents. Additionally, baicalin (0.3-30 microM) reduced the amplitude of VDCC currents in a concentration-dependent manner and abolished VDCC activator Bay K8644-enhanced (0.1 microM) currents. Baicalin produced MA relaxation by activating BK(Ca) and inhibiting VDCC channels by endothelium-independent mechanisms and by stimulating the cGMP/PKG and cAMP/PKA pathways.

Topics: Animals; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Endothelium, Vascular; Female; Flavonoids; Mesenteric Arteries; Patch-Clamp Techniques; Potassium Channels, Calcium-Activated; Rats; Rats, Sprague-Dawley; Scutellaria baicalensis

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.

Topics: Animals; Antioxidants; Aorta; Calcium; Cyclic GMP; Endothelium, Vascular; Flavanones; Flavonoids; Male; Nitric Oxide; Rats; Rats, Sprague-Dawley; Vasodilation