Differences in time-related cardiopulmonary responses to hypoxia in three rat strains.
The cardiopulmonary profile of three rat strains (Sprague-Dawley, Wistar and High altitude-sensitive) was compared upon exposure to hypoxia (9% O2) for 0, 7 or 14 days. No differences were observed among the in vitro contractile (ET-1) and relaxant (carbachol) responses of pulmonary artery isolated from the three strains during normoxia. Chronic hypoxia decreased ET-1 contractile responses and diminished relaxant responses to carbachol similarly in all strains. In Sprague-Dawley, Wistar and High altitude-sensitive rats, pulmonary arterial pressure rose time-dependently and was elevated by 108%, 116% and 167%, respectively, after 14 days of hypoxia compared to normoxic controls. Right ventricular hypertrophy was increased by 51%, 93% and 55%, respectively, at 14 days. Hypoxia-induced hypertrophy and medial thickening in the pulmonary vasculature were more pronounced in High altitude-sensitive rats. Sprague-Dawley exhibited hypoxia-induced airway hyperresponsiveness to intravenous methacholine, but there were no hypoxia- or strain-related differences in in vitro tracheal contractility. Although each strain exhibited greater sensitivity for a particular hypoxia-induced parameter, pulmonary vascular functional and structural changes suggest that High altitude-sensitive rats represent a choice model of hypoxia-induced pulmonary hypertension.
Department of Pulmonary Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
S
S
Bochnowicz
R R
RR
Osborn
M A
MA
Luttmann
C
C
Louden
T
T
Hart
D W
DW
Hay
D C
DC
Underwood
D000531:Altitude; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000494:pharmacology; D016232:Endothelins / Q000097:blood; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006984:Hypertrophy; D017380:Hypertrophy, Right Ventricular / Q000209:etiology; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013045:Species Specificity; D014132:Trachea / Q000187:drug effects / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D019332:Endothelin-1; D016232:Endothelins; D016210:Methacholine Chloride; D002217:Carbachol