Two exogenous NO donors were used to act as substitutes for impaired endogenous nitric oxide (NO) production due to inhibition of NO synthase in rats. Six weeks' lasting inhibition of NO synthase by NG-nitro-L-arginine methyl ester (L-NAME) induced stabilized hypertension. Simultaneously administered isosorbide-5-mononitrate did not prevent the development of hypertension. Molsidomine, administered concomitantly with L-NAME, significantly attenuated the BP increase. However, BP was still found to be moderately increased compared to the initial values. Remarkable alterations in the geometry of the aorta, carotid and coronary artery found in NO-deficient hypertension were prevented in rats administered L-NAME plus molsidomine at the same time. In spite of 6 weeks' lasting inhibition of NOS, the NOS activators acetylcholine and bradykinin induced BP decrease; the maximum hypotensive value did not differ from the values recorded in the controls or in animals treated with L-NAME plus molsidomine. Notably enough, the hypotension was similar to that found in rats administered L-NAME alone for six weeks. After NO synthase inhibition, Isosorbide-5-mononitrate does not substitute and molsidomine substitute only partially the impaired endogenous NO production., M. Gerová, F. Kristek., and Obsahuje bibliografii
It has been suggested that increase in acute nitric oxide (NO) or cyclic guanosine monophosphate production may be involved in cardioprotection induced by chronic hypoxia (CH). We studied the effect of NO donor molsi domine and phosphodiesterase type 5 inhibitor sildenafil on myocardial ischemia/reperfusion (I/R) injury in rats adapted to CH. Male Wistar rats were exposed to continuous hypoxia in a normobaric chamber (10 % O 2 , 4 weeks). Rats received either saline, mol sidomine (10 mg/kg body weight, i.v.) or sildenafil (0.7 mg/kg body weight, i.v.) 30 min before ischemia. Control rats were kept under normoxia and treated in a corresponding manner. Adaptation to CH increased the myocardial ischemic tolerance. Acute treat ment with either molsidomine or sildenafil significantly reduced infarct size in normoxic rats and further enhanced cardioprotection induced by CH. However, the cardioprotective effect of CH on I/R injury was not additive to the cardioprotection provided b y the drugs., P. Alánová, F. Kolář, B. Ošťádal, J. Neckář., and Obsahuje bibliografii