Pulmonary artery contractility in pneumonia: role of cyclooxygenase products and nitric oxide.
The purpose of this study was to determine the effects of aminoguanidine (AG) and meclofenamate (MEC) on depressed contractility of small pulmonary artery (PA) rings isolated from a rat model of acute Pseudomonas pneumonia. Contractility of PA rings from lungs of control or pneumonia rats was assessed in vitro by obtaining cumulative concentration-contraction curves to potassium chloride (KCl), phenylephrine (PE), and prostaglandin F2alpha (PGF2alpha) on rings treated with or without MEC (1.0 microM), AG (100 microM), or AG + MEC. Vessels from pneumonia rats exhibited significant attenuation of the contractile responses to KCl, PE, and PGF2alpha. MEC restored the KCl and PGF2alpha contractile responses to control values, but had no effect on the attenuated PE contractile response. In contrast, AG restored the PE contractile response, and only partially affected contractile responses to KCl and PGF2alpha, MEC + AG restored the contractile responses of all three agonists. We conclude that both excess nitric oxide (NO) and cyclooxygenase products contribute to the depressed pulmonary vascular contractility observed in rats with acute pneumonia. The relative importance of NO and cyclooxygenase products in this phenomenon depends on the contractile agonist studied.
Yaghi
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The A.C. Burton Vascular Biology Laboratory, Division of Respiratory Medicine, London Health Sciences Centre, Ontario, Canada.
McCormack
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D000704:Analysis of Variance; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018410:Pneumonia, Bacterial / Q000201:enzymology / Q000503:physiopathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011552:Pseudomonas Infections / Q000201:enzymology / Q000503:physiopathology*; D011550:Pseudomonas aeruginosa; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D006146:Guanidines; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D011451:Prostaglandin-Endoperoxide Synthases; C004479:pimagedine