cyclic-gmp and azepexole

The thoracic aorta was taken from nephrotic rats on the 40th day after a single i.v. injection of daunomycin (10 mg/kg). In the endothelium-intact aorta, the contractions induced by norepinephrine or B-HT 933, an alpha-2 adrenoceptor agonist, were significantly greater in nephrotic rats than in normal animals. However, such a difference was not observed in the KCl- or U46619-induced contractions. The difference in norepinephrine-induced contraction between nephrotic and normal preparations was enhanced by zaprinast, a cyclic GMP phosphodiesterase inhibitor. The contractions elicited by norepinephrine and B-HT 933 were potentiated by either removal of the endothelium or pretreatment with methylene blue, a guanylate cyclase inhibitor. The difference in the contractile response to these agonists between nephrotic and normal preparations was eliminated completely by either treatment. The cyclic GMP level in the endothelium-intact aorta in the presence of zaprinast was significantly lower in nephrotic rats than in normal animals. In the presence of zaprinast, norepinephrine, but not B-HT 933, caused an increase in the cyclic GMP level, which was abolished completely by pretreatment with prazosin, but not by yohimbine. These results suggest that the augmented contractile response to norepinephrine observed in nephrotic aorta may be due to the decrease in the stimulated release of endothelium-derived relaxing factor from the endothelial cells via the stimulation of endothelial alpha-1 adrenoceptors, whereas the augmented response to B-HT 933 may be due, at least in part, to the decrease in spontaneously released endothelium-derived relaxing factor.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adrenergic alpha-Agonists; Animals; Azepines; Cyclic GMP; Endothelium, Vascular; Male; Muscle Contraction; Nephrosis; Nitric Oxide; Norepinephrine; Potassium Chloride; Prostaglandin Endoperoxides, Synthetic; Rats; Rats, Sprague-Dawley; Thromboxane A2