title: Prostacyclin-mediated compensatory mechanism in the coronary circulation during acute NO synthase blockade.
abstract: 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.
authors.affiliation: Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Ulloi út 78/a, H-1082 Budapest, Hungary. zlacza@mac.com
authors.forename: Zsombor
authors.initials: Z
authors.lastname: Lacza
authors.forename: László
authors.initials: L
authors.lastname: Dézsi
authors.forename: Krisztina
authors.initials: K
authors.lastname: Káldi
authors.forename: Eszter M
authors.initials: EM
authors.lastname: Horváth
authors.forename: Péter
authors.initials: P
authors.lastname: Sándor
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Benyó
mesh_terms: 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
chemical_list: 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