Vasodilatory effect of kaempferol-7-O-α-L-rhamnopyranoside via NO-cGMP-PKG signaling.

Hypertension is one of the major causes of mortality. Though a host of drugs are available for the treatment of hypertension, majority have been linked to adverse side effects, necessitating the need for research into natural compounds with fewer side effects. Kaempferol-7-O-α-L-rhamnopyroside (KR) is a glycosylated flavone with neuroprotective and anti-inflammatory effects. However, no available literature exists on its vasodilatory effect. This study examined the pharmacological effect of KR on vasodilation/vasorelaxation and its mechanism of action in endothelial cells and rat thoracic aorta. Treatment of phenylephrine (PE; 2 × 10-6 M)-pre-contracted aortic rings with KR induced endothelium-dependent relaxation, which was suppressed by NG-nitro-l-arginine methyl ester (L-NAME; 10-4 M), (nitric oxide synthase (NOS) inhibitor). Phosphorylation of eNOS in human umbilical vein endothelial cells (HUVECs) was increased after exposure to KR. Pre-treatment of aortic rings with the cyclic GMP (cGMP) inhibitors; methylene blue (MB; 10-5 M) and 1-H-[1,2,4]-oxadiazolole-[4,3-α]-quinoxalin-10-one, (ODQ; 10-6 M) suppressed the KR-induced vasodilation. Furthermore, KR also increased protein kinase G (PKG) levels whereas it suppressed levels of phosphorylated myosin light chain (MLC) and protein kinase C (PKC) in aortic rings. These results suggest that KR induces endothelium-dependent vasorelaxation via the NO-cGMP-PKG pathway.