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Copyright © 2000 by Institute of Pharmacology Polish Academy of Sciences |
Pol. J. Pharmacol., 2000, 52, 375-381 ISSN 1230-6002 |
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Influence of nitric oxide on the cardiovascular action of secretin in intact rats. Part B. Does nitric oxide influence the effect of secretin on isolated heart function?
E.M. SITNIEWSKA, R.J. WIŚNIEWSKA, K. WIŚNIEWSKI. Pol. J. Pharmacol., 2000, 52, 375-381. The present study was designed to examine the effect of absence or excess of NO on secretin-mediated responses in the isolated heart. This problem was investigated using the modified Langendorff’s method. Secretin administered at two higher doses increased the cardiac contraction amplitude (p < 0.05), but did not change the heart rate and coronary outflow. NO was depleted from experimental system by perfusion of the isolated heart with NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester) at 10 µM. It caused a significant decrease in coronary outflow (p < 0.01) and the tendency to bradycardia (p > 0.05) with no change in cardiac contraction amplitude. L-NAME abolished the positive inotropic effect of the medium secretin dose and preserved the inotropic effect of the highest dose of the peptide. It reversed the tendency to decrease coronary outflow induced by secretin (and L-NAME) given separately. To study the effect of NO excess, we applied the substrate for NO synthesis, amino acid L-arginine (L-arg) (100 µM) or exogenous donor of NO - sodium nitroprusside (SNP) (100 mM). Both substances did not affect the isolated heart function. L-arg did not change the effect of secretin, however it abolished non significant decrease in coronary outflow evoked by the highest dose of secretin. SNP preserved the positive inotropic action of the peptide and expressively reversed the negative values of coronary outflow observed after its co-administration with the highest dose of secretin. These results indicate that both the absence and excess of NO change the cardiac effect of secretin in the same direction. Key words: secretin, nitric oxide, isolated heart, rats |
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