Effect of heme oxygenase induction by NO donor on the aortic contractility

Carbon monoxide (CO) binds to soluble guanylate cyclase to lead its activation and elicits smooth muscle relaxation. The vascular tissues have a high capacity to produce CO, since heme oxygenase-2 (HO-2) is constitutively expressed in endothelial and smooth muscle cells, and HO-1 can be greatly up-regulated by oxidative stress. Moreover, the substrate of HO, heme, is readily available for catalysis in vascular tissue. Although the activation of heme oxygenase pathway under various stress conditions may provide a defence mechanism in compromised tissues, the specific role of HO-1-derived CO in the control of aortic contractility still remains to be elucidated. The present study was done to determine the effect of HO-1 induction on the aortic contractility. Thus, the effects of incubation of aortic tissue with S-nitroso-N-acetylpenicillamine (SNAP) for 1 hr on the aortic contractile response to phenylephrine were studied. The preincubation with SNAP resulted in depression of the vasoconstrictor response to phenylephrine. This effect was restored by HO inhibitor or methylene blue but not by NOS inhibitor. The attenuation of vascular reactivity by preincubation with SNAP was also revealed in endothelium-free rings. AlF4--evoked contraction in control did not differ from that in SNP-treated group. These results suggest that increased production of CO was responsible for the reduction of the contractile response to phenylephrine in aortic ring preincubated with SNAP and this effect of SNAP was independent on endothelium.

The Effect of Saponin on the Vascular Contractility of the Rabbit Aortic Ring

PURPOSE: There have been conflicting reports on vascular response to Panax ginseng. The conflicting reports may be due to difference of ingredient of Panax ginseng. The aim of the present study was to investigate the effect of saponin, the main ingredient of Panax ginseng, on the vascular contractility. METHODS: The rabbit aortic rings were cut and mounted on the force transducer to record an isometric tension on polygraph. To elucidate the mechanism of saponin effect on vascular smooth muscle, the contractility of the vascular smooth muscle were measured under varying experimental condition. RESULTS: 1) When the aortic rings were precontracted with norepinephrine, saponin caused biphasic(initial relaxation-sustained contraction) dose-response in the endothelium dependent manner. But saponin had no effect on the resting tension. 2) When EDRF inhibitors such as methylene blue(10(-5)M), hemoglobin(10(-5)M), N-omega-nitro-L-arginine(100microM) were added to precontracted ring with norepinephrine, the initial relaxation caused by 2mg% saponin was inhibited. 3) When Ca(2+)-channel blocker, nifedipine(5x10(-7)M), was added to precontracted rings with norepinephrine, the sustsined contraction by saponin was inhibited. 4) When hemoglobin(10(-5)M) was added to precontracted rings with norepinephrine, the contractility by norepinephrine was increased and this effect was further augmented by 2mg% saponin. CONCLUSIONS: From the above results, it may be concluded that saponin stimulated the release of both an endothelium-dependent relaxing factor and endothelium-dependent contracting factor.

Effects of mastoparan on a vascular contractility in rabbit aorta

Mastoparan is an amphiphilic tetradecapeptide derived from wasp venom which activates G-proteins. Several secondary effects have been attributed to this peptide, including activation of phospholipase and phosphatidylinositol kinase. The aim of the present study was to investigate the effects of mastoparan on vascular contractility. Rabbit aortic rings were cut and mounted on a force transducer to record isometric tension on a polygraph. The effects of mastoparan were then investigated on the contractile responses in the isolated rabbit aorta with or without endothelium. The results were summarized as follows; 1. Mastoparan caused biphasic response, a transient relaxation followed by a further contraction, in norepinephrine (NE)-precontracted ring with endothelium. These effects were not observed in the aorta in the absence of endothelium. 2. Mastoparan-induced transient relaxation was significantly inhibited by treatment with a N-omega-nitro-L-arginine or methylene blue. 3. When an inhibitor of phospholipase C, neomycin was added to the precontracted aortic ring with NE, the transient relaxation induced by mastoparan was inhibited, but sustained contraction was not inhibited. 4. When an inhibitor of phospholipase A2, quinacrine and inhibitor of the cyclooxygenase pathway, indomethacin, were added to a precontracted ring with NE, the transient relaxation induced by mastoparan was not inhibited, but sustained contraction was inhibited. 5. Mastoparan induced a contraction of the aorta either with or without endothelium. Indomethacin and nifedipine inhibited mastoparan-induced contraction. From the above results, we concluded that mastoparan acts on the endothelium and modifies the release of endothelium-derived relaxing factors such as nitric oxide and also endothelium-derived contracting factors such as metabolites of arachidonic acid.