Prostacyclin-mediated compensatory mechanism in the coronary circulation during acute NO synthase blockade.
Nitric oxide (NO) in contrast to most prostanoids, plays a major role in the maintenance of coronary arterial tone under physiological conditions. However, in case of endothelial damage or other NO-depleting situations the importance of other vasodilating mechanisms may be increased. The aim of the present study was to investigate the crosstalk between the L-arginine - NO and the prostanoid systems in isolated rat hearts. Coronary flow and cardiac dynamics were measured in a standard Langendorff perfusion system. Application of indomethacin in the perfusion media failed to change coronary flow. Administration of L-NA, however, significantly decreased coronary flow by 24.8 +/- 2.3% (p < 0.01 vs. untreated control). In the presence of indomethacin, L-NA decreased coronary flow to an even greater extent by 35.8 +/- 5.2% (p < 0.05 vs. L-NA alone). Treatment of the preparations with L-NA or indomethacin failed to change cardiac work, coapplication of both drugs together, however, decreased cardiac work by 45 +/- 11% (p < 0.05 vs. untreated control). Heart rate remained constant throughout the experimental period and did not differ significantly between the treatment groups. The prostacyclin content of the effluent from the L-NA treated hearts was significantly higher than that of controls. We conclude that in case of decreased NO levels in the coronary circulation, arterial tone is maintained by prostacyclin production.
Lacza
Zsombor
Z
Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Ulloi út 78/a, H-1082 Budapest, Hungary. zlacza@mac.com
Dézsi
László
L
Káldi
Krisztina
K
Horváth
Eszter M
EM
Sándor
Péter
P
Benyó
Zoltán
Z
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D004338:Drug Combinations; D011464:Epoprostenol / Q000032:analysis / Q000502:physiology*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
D004338:Drug Combinations; D009569:Nitric Oxide; D001120:Arginine; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D007213:Indomethacin