Vasorelaxation, nitric oxide-dependent

Fig. 4.1. Cellular model illustrating cell types in vascular wall involved in vasorelaxation induced by SERMs. Putative targets of SERMs are indicated within cyan tags. SERMs directly affect L-type VDCC, BK fil subunit in smooth muscle cells, and ER in endothelial cells. L-type VDCC L-type voltage-dependent calcium channel BK calcium-activated large conductance K+ channel PKG protein kinase G eNOS endothelial nitric oxide synthase GC soluble guanylate cyclase cGMP cyclic GM P V electrochemical membrane potential ER estrogen receptor. See text for further details...

Christopher TA, Lopez BL, Stillwagon JC, Gao F, Gao E, Ma XL, Ohlstein EH, Yue TL (2002) Idoxifene causes endothelium-dependent, nitric oxide-mediated vasorelaxation in male rats. Eur J Pharmacol 446(1-3) 139-143... 

Idoxifene causes endothelium-dependent, nitric oxide-mediated vasorelaxation in male rats. Eur J Pharmacol 446 139-143... 

Vascular and hematologic effects Ginkgo exerts vascular effects through at least two mechanisms inhibition of platelet-activating factor (PAF) and nitric oxide mechanisms. Ginkgo extract relaxes the porcine basilar artery in a concentration-dependent and partly endothelium-dependent manner (Chen et al. 1997). It also enhances vasorelaxation created by transmural nerve stimulation in arteries with and without the endothelium intact, and is prevented by nitro-L-arginine, indicating that the effect is mediated by nitric oxide. 

Ginseng s mechanism of vasorelaxation and nitric oxide release is probably by conversion of L-arginine to L-citrulline (Kim H et al. 1992). Ginseng saponin induces relaxation of the corpus cavernosum smooth muscle in a dose-dependent manner (Kim HJ et al. 1998). This effect is... 

Lorenz, M., Wessler, S., Follmann, E., Michaelis, W., Dusterhoft, T., Baumann, G., Stangl, K, and Stangl, V., A constituent of green tea, epigallocatechin-3-gallate, activates rndothelial nitric oxide synthase by a phosphatidylinositol-3-OH-kinase-, cAMP-dependent protein kinase-, and Akt-dependent pathway and leads to endothelial-dependent vasorelaxation, J. Biol Chem., 279, 6190, 2004. 

Besides cell signaling, superoxide production by nonphagocytic cells may exhibit damaging activity through the interaction with nitric oxide to form peroxynitrite, toxic effects of which were considered in Chapter 21. On the other hand, a decrease in NO concentration may result in endothelial dysfunction due to reduction in endothelium-dependent vasorelaxations... 

Dessy, C., Moniotte, S., Ghisdal, P., Havaux, X., Noirhomme, R, and Balligand, J.L. 2004. Endothelial p3-adrenoceptors mediate vasorelaxation of human coronary microarteries through nitric oxide and endothelium-dependent hyperpolarization. Circulation 110 948-954. 

Archer SL, Huang JM, Hampl V, Nelson DP, Shultz PJ and Weir EK, Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase. Proc Natl Acad Sci USA 91(16) 7583-7, 1994. 

Hayakawa H, Hirata Y, Suzuki E, SugimotoT, Matsuoka H, Kikuchi K, Nagano T, Hirobe M Mechanisms for altered endothelium-dependent vasorelaxation in isolated kidneys from experimental hypertensive rats. Am J Physiol 264 1535-41,1993 Hirata Y, Hayakawa H, Kakoki M,Tojo A, Suzuki E, Nagata D, Kimura K,Goto A, Kikuchi K, NaganoT, Hirobe M, Omata M Receptor subtype for vasopressin-induced release of nitric oxide from rat kidney. Hypertension 29 58-64,1997 Hirata Y, Hayakawa H, Suzuki E, Omata M Does endothelin work as an intrarenal mechanism to alter pressure natriuresis in spontaneously hypertensive rats J Hypertens 12 251-7,1994... 

Archer, S. L., Huang, J. M. C., HampI, V., Nelson, D. P., Shultz, P. J., and Weir, E. K. (1994). Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase. Proc. Natl. Acad. Set. U.S.A. 91,7583-7587. Beckman, J. S., Ye, Y. Z., Anderson, P. G., Chen, J., Accavitti, M. A., Tarpey, M. M., and White, C. R. (1994). Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry. Biol. Chem. Hoppe-Seyler 375, 81-88. Bhagyalakshmi, A., Berthiaume, F., Reich, K. M., and Frangos, J. A. (1992). Fluid shear stress stimulates membrane phospholipid metabolism in cultured human endothelial cells. J. Vase. Res. 29, 443-449. 

We evaluated whether the Mn(ii)-based SOD mimics could potentiate the levels of nitric oxide, a potent vasorelaxant. Superoxide reacts with nitric oxide in a diffusion-controlled manner to produce peroxynitrite. By catalyzing the dismu-tation of superoxide, SOD mimics would be expected to increase nitric oxide levels. The SOD mimic SC-52608 enhanced nitric oxide levels (as assessed by cyclic GMP activity) in rat lung fibroblasts in a dose-dependent manner. SC-52608 induced the relaxation of preconstricted rat aortic rings. The aortic ring relaxation was endothelium-dependent and inhibitable by a nitric oxide synthase inhibitor. Intravenous administration of SC-52608 into conscious rats resulted in a transient, dose-dependent decrease in blood pressure. The results are consistent with the SOD mimic SC-52608 potentiating levels of nitric oxide, which causes the observed relaxation of the aortic rings and the decrease in blood pressure. 

Anandamide has been shown to act via the release of endothelium-derived nitric oxide in the rat kidney (Dentsch et al., 1997). A range of human blood vessels and the right atrium have also been shown to release nitric oxide in response to anandamide (Bilfinger et al., 1998). However, in many instances (see Randall etal., 1996 White and Ehley, 1997 Jarai etal., 1999), vasorelaxant responses to anandamide are insensitive to inhibition of nitric oxide synthase. In HUVECs, Maccarrone et al. (2000) reported that anandamide and the CB agonist, HU210, both cause an upregulation of the expression and activity of the inducible nitric oxide synthase. Mukhopadhyay et al. (2002) demonstrated that the endothelium-dependent component was G protein coupled and mediated via nitric oxide, whereas the endothehum-independent component was due to activation of vanilloid receptors, at least in rabbit aortic rings. 

Andriambeloson E, Kleschyov AL, Muller B, Beretz A, Stoclet JC, Andriantsitohaina R (1997) Nitric oxide production and endothelium-dependent vasorelaxation induced by wine polyphenols in rat aorta. Br J Pharmacol 120(6) 1053-1058... 

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