title: Macro- and micropulmonary hemodynamic changes to nitric oxide blockade in monocrotaline-induced pulmonary hypertension in rats--an in vivo approach.
abstract: OBJECTIVE
  Data on the role of nitric oxide (NO) in monocrotaline (MC)-induced pulmonary hypertension of rats have all been derived from in vitro measurements. In vivo pulmonary hemodynamics and microvascular responses to NO blockade in MC-treated rats have not been reported. The current study evaluated the role of NO in live MC-treated rats.
  
  
  METHODS
  Male Sprague-Dawley rats (n = 29) were divided into saline control and MC-treated groups. Three to 4 weeks after either saline or MC injection, pulmonary hemodynamics were measured using pulmonary arterial catheter and thermodilution techniques. Pulmonary microvascular diameter changes were assessed using an intravital microscope.
  
  
  RESULTS
  Three to 4 weeks after subcutaneous injection of MC (50 mg/kg), MC-treated rats showed elevated pulmonary arterial pressure compared to control rats (23.6 +/- 2.9 mm Hg vs 14.5 +/- 0.8 mm Hg). N(omega)-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg, intravenously), an NO synthase inhibitor, produced significant increases in pulmonary arterial pressure and total pulmonary vascular resistance compared to control rats (12.3 +/- 2.5 mm Hg vs 1.0 +/- 0.9 mm Hg; 0.21 +/- 0.04 mm Hg/mL/min vs 0.05 +/- 0.02 mm Hg/mL/min, p < 0.05). Intravital microscopic observation of the subpleural vessels showed significant vasoconstriction in medium-sized (> 40 microm) pulmonary arterioles of MC-treated rats following L-NAME administration (58.4 +/- 3.6 microm vs 47.1 +/- 3.4 microm, p < 0.05) while no significant diameter changes were found in either the small-sized (< 40 microm) pulmonary arterioles or pulmonary venules. Diameters of pulmonary arterioles and venules in control rats were not affected by L-NAME administration.
  
  
  CONCLUSIONS
  Pulmonary arterial pressure and pulmonary vascular resistance increased after NO blockade in live MC-treated rats. The site of vasoconstriction after NO blockade included medium-sized pulmonary arterioles but not small-sized pulmonary arterioles. This study has provided both macro- and microhemodynamic evidence of a modulatory role of NO in live MC-treated rats.
authors.affiliation: Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chang-Wen
authors.initials: CW
authors.lastname: Chen
authors.forename: Ching-Min
authors.initials: CM
authors.lastname: Wang
authors.forename: Cheng-Hung
authors.initials: CH
authors.lastname: Lee
authors.forename: Tzuen-Ren
authors.initials: TR
authors.lastname: Hsiue
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Kuo
authors.forename: Han-Yu
authors.initials: HY
authors.lastname: Chang
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D016686:Monocrotaline / Q000009:adverse effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D016686:Monocrotaline; D019331:NG-Nitroarginine Methyl Ester