Anti-platelet agents reduce morphological changes of chronic hypoxic pulmonary hypertension.
The pathophysiologic mechanism by which chronic hypoxia causes pulmonary hypertension is unknown. If anti-platelet agents, or other pharmacologic interventions, altered the pulmonary vascular changes induced by hypoxia, information concerning the pathogenesis of the pulmonary hypertension or the potential therapeutic usefulness of the drugs might be obtained. In Study 1, rats exposed to chronic hypobaric hypoxia (PB = 520 mmHg) had a pulmonary arterial medial thickness of 6.7 +/- 0.6 mu compared to 4.1 +/- 0.2 mu* for control, normoxic rats (*p less than 0.05). Administration of dipyridamole (2mg/kg/day), or sulfinpyrazone (11 mg/kg/day) in the drinking water reduced the medial thickness to 5.0 +/- 0.3 mu* and 5.4 +/- 0.5 mu* respectively, thus suggesting the possible involvement of platelets in the response of the media to chronic hypoxia. In Study 2, hypoxic rats treated with the calcium blocker, flunarizine, were found to have less medial hypertrophy than a control group of hypoxic rats. This observation suggests that a decrease in transmembrane calcium flux may also reduce medial hypertrophy.
Keith
I M
IM
School of Veterinary Medicine, University of Wisconsin, Madison.
Will
J A
JA
Huxtable
R J
RJ
Weir
K
K
D000818:Animals; D004176:Dipyridamole / Q000494:pharmacology*; D005444:Flunarizine / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles; D006976:Hypertension, Pulmonary / Q000473:pathology* / Q000503:physiopathology; D000860:Hypoxia / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000473:pathology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013442:Sulfinpyrazone / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D005444:Flunarizine; D013442:Sulfinpyrazone