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.

Tettey CO ，Yang IJ ，Shin HM 《-》

Vasodilatory effects of cinnamic acid via the nitric oxide-cGMP-PKG pathway in rat thoracic aorta.

Cinnamic acid (CA) and its derivatives have a broad therapeutic spectrum that includes antimicrobial, antifungal, and antitumoral activities. However, the vasodilative effect of CA has not been demonstrated. The present study characterizes the vasodilative activity and the mechanism of CA in rat thoracic aorta. The vasomotion of aortic strips following CA treatment was measured in an organ bath system. In addition, vascular strips and human umbilical vein endothelial cells (HUVECs) were used in organ bath, Western blot, nitrite, and cyclic guanosine monophosphate (cGMP) measurements. CA relaxed phenylephrine-precontracted aortic strips in an endothelium-dependent manner. Pretreatment of the endothelium-intact aortic strips with N(G) -nitro-l-arginine methyl ester (10(-4)  M), 1 H-[1,2,4]-oxadiazolole-[4,3-a] quinoxalin-10-one, (10(-6)  M) and methylene blue (10(-5)  M) inhibited CA-induced vasorelaxation. CA also increased the phosphorylation of endothelial nitric oxide synthase and nitric oxide generation in a concentration-dependent manner in HUVECs. In addition, cGMP generation and cGMP-dependent protein kinase G (PKG) expression in aortic strips were increased by CA treatment. Furthermore, CA-induced vasorelaxation was inhibited by the PKG inhibitor KT5823 (0.3 μM) and the Ca(2+) -activated K(+) channel inhibitor tetraethylammonium (10(-3)  M). These findings suggest that CA exerts an endothelium-dependent vasodilation effect via the nitric oxide-cGMP-PKG-mediated pathway in rat thoracic aorta.

Kang YH ，Kang JS ，Shin HM 《-》

Cinnamyl alcohol attenuates vasoconstriction by activation of K⁺ channels via NO-cGMP-protein kinase G pathway and inhibition of Rho-kinase.

Kang YH ，Yang IJ ，Morgan KG ，Shin HM ... -  《-》

Mantidis ootheca induces vascular relaxation through PI3K/AKT-mediated nitric oxide-cyclic GMP-protein kinase G signaling in endothelial cells.

Kim HY ，Lee YJ ，Han BH ，Yoon JJ ，Ahn YM ，Hong MH ，Tan R ，Kang DG ，Lee HS ... -  《-》

Blood pressure lowering effect and vascular activity of Phyllanthus niruri extract: The role of NO/cGMP signaling pathway and β-adrenoceptor mediated relaxation of isolated aortic rings.

Phyllanthus niruri have a long history of use in the traditional treatment of various ailments including hypertension. Literature reports have indicated that it is a potent antihypertensive herbal medication used traditionally. This study was carried out to investigate the antihypertensive and vasodilatory activity of four solvents extracts of P. niruri namely; petroleum ether (PEPN), chloroform (CLPN), methanol (MEPN) and water (WEPN), with the aim of elucidating the mechanism of action and identifying the phytochemical constituents. Male Spontaneous Hypertensive Rats (SHRs) were given oral gavage of P. niruri extract daily for two weeks and the blood pressure was recorded in vivo. We also determine the vasodilation effect of the extracts on rings of isolated thoracic aorta pre-contracted with phenylephrine (PE, 1 μM). Endothelium-intact or endothelium-denuded aorta rings were pre-incubated with various antagonists like 1H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 μM) and Methylene blue (MB 10 μM), sGC inhibitors; Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 10 μM) a nitric oxide synthase (NOS) inhibitor; atropine (10 μM), a cholinergic receptor blocker; indomethacin (10 μM), a cyclooxygenase inhibitor and various K+ channel blockers such as glibenclamide (10 μM) and tetraethyl ammonium (TEA 10 μM) for mechanism study. SHRs receiving P. niruri extracts showed a significant decrease in their blood pressure (BP) when compared to the baseline value, with PEPN being more potent. The extracts (0.125-4 mg/mL) also induced vasorelaxation on endothelium-intact aorta rings. PEPN elicited the most potent maximum relaxation effect (Rmax). Mechanism assessment of PEPN showed that its relaxation effect is significantly suppressed in endothelium-denuded aorta rings. Pre-incubation of aorta rings with atropine, L-NAME, ODQ, indomethacin, and propranolol also significantly attenuated its relaxation effect. Conversely, incubation with TEA and glibenclamide did not show a significant effect on PEPN-induced relaxation. This study indicates that the antihypertensive activity of P. niruri extract is mediated by vasoactive phytoconstituents that dilate the arterial wall via endothelium-dependent pathways and β-adrenoceptor activity which, in turn, cause vasorelaxation and reduce blood pressure.

Bello I ，Usman NS ，Dewa A ，Abubakar K ，Aminu N ，Asmawi MZ ，Mahmud R ... -  《-》