Hypoxic and pharmacological preconditioning preserves vasomotor response of porcine coronary artery.
Vasomotor response of the coronary artery depends on both endothelial and smooth muscle cells. Response is altered by hypoxia-reoxygenation-induced damages. Hypoxic preconditioning and pharmacological preconditioning as well can prevent these alterations. We compared the effectiveness of both types of preconditioning against hypoxia-reoxygenation-induced changes in vasomotor response of the isolated artery. Porcine arterial rings (3-4 mm wide) were cut from the left anterior descending porcine coronary artery and placed in Krebs-Henseleit solution. In order to obtain control response of the arteries, we contracted arterial rings with 20 mM KCl before ("standard contraction") and after 60-min hypoxia and 30-min reoxygenation. In other groups, nitric oxide-synthase and cyclooxygenase were inhibited. Then, the rings were pre-contracted with U46619 and relaxed by cumulative addition of the substance P. Contractions and relaxations of non-preconditioned and hypoxically or pharmacologically preconditioned rings were compared. Hypoxic preconditioning was performed by two periods of 5-min hypoxia and 10-min reoxygenation. For pharmacological preconditioning, we used application of adenosine, adrenaline, acetylcholine and angiotensin II. Analysis was performed with one-way ANOVA, followed by Dunnett's Multiple Comparison Test. After hypoxia-reoxygenation, in non-preconditioned rings KCl-induced contractions were significantly increased compared to standard contraction. Relaxations of hypoxically and pharmacologically preconditioned rings (expressed as percentages of U46619-induced pre-contraction) were significantly decreased (p < 0.01) compared to hypoxic but not to normoxic rings. Hypoxic and pharmacological preconditioning may preserve contraction and endothelium-dependent relaxation of porcine coronary artery after long-lasting hypoxia-reoxygenation.
Kuzner
Jernej
J
Department of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia. jernej.kuzner@vf.uni-lj.si
Drevensek
Gorazd
G
Gersak
Borut
B
Budihna
Metka
M
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology*; D004837:Epinephrine / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D000804:Angiotensin II; D019335:Nitroarginine; D013373:Substance P; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000241:Adenosine; D000109:Acetylcholine; D010100:Oxygen; D004837:Epinephrine