To investigate the mechanism by which the total alkaloid fraction obtained from the root bark of Solanum paludosum (FAT-SP) acts as a vasorelaxant agent on rat thoracic aorta.
Rings of rat aorta were suspended in organ bath containing Krebs solution at 37 掳C, bubbled with carbogen mixture (95%O2 and 5%CO2) under a resting tension of 1 g. Isometric contractions were measured using a force transducer coupled to an amplifier and a microcomputer.
FAT-SP has been found cause relaxation of the aortic rings pre-contracted with phenylephrine (Phe) in a concentration-dependent manner, in the presence and absence of endothelium. This effect was more potent on the endothelium-intact aorta. In the presence of endothelium, neither indomethacin (non-selective cyclooxygenase inhibitor) nor atropine (non-selective muscarinic receptor antagonist), produced significant changes on the relaxation response. On the other hand, in the presence of calmidazolium (a calmodulin inhibitor), N-nitro-l-arginine methyl ester (l-NAME, nitric oxide synthase inhibitor), hydroxocobalamin (HDX) (scavenger of free-radical nitric oxide), 1-H-[1,2,4]-oxadiazolo-[4,3a]-quinoxalin-1-one (ODQ, selective blocker of soluble guanylate cyclase), Rp-8-bromo-尾-phenyl-1,N2-ethenoguanosine 3鈥?5鈥?cyclic monophosphorothioate sodium salt hydrate (Rp-8-Br-PET-cGMPS, competitive inhibitor of cGMP-dependent protein kinase G) or TEA+ (tetraethylammonium, nonselective potassium channel blocker), the vasorelaxant effect was significantly reduced, suggesting the involvement of NO/sCG/PKG pathway and potassium channel opening in vasorelaxant action of the FAT-SP.
The mechanism of vasorelaxant activity of the FAT-SP on rat aorta involves both NO/sCG/PKG pathway and potassium channels.