Reduction of chronic hypoxic pulmonary hypertension in the rat by an inhibitor of collagen production.
Chronic hypoxic pulmonary hypertension in the rat is associated with increased collagen and elastin in the pulmonary artery. We investigated whether excess vascular collagen contributes to chronic hypoxic pulmonary hypertension by administering the proline analogue cis-4-hydroxy-L-proline (cHyp), an agent relatively specific for inhibiting collagen production, to rats exposed to chronic hypoxia. Sprague-Dawley rats (weighting 200 g) were exposed to air or hypoxia (10% O2-90% N2) for 3 wk. Groups studied were: air-exposed injected with saline, air-exposed injected with cHyp, hypoxic injected with saline, and hypoxic injected with cHyp. At the end of 3 wk, we measured mean right ventricular pressure (RVP) of animals breathing room air and hydroxyproline and desmosine contents of the main pulmonary artery trunk. Hypoxia increased RVP from 13 +/- 1 to 27 +/- 1 mm Hg (p less than 0.05); cHyp partially prevented this increase since RVP was 17 +/- 1 mm Hg (p less than 0.05). There was no effect of cHyp on cardiac output. Hypoxia increased collagen from 0.9 +/- 0.1 to 2.0 +/- 0.3 mg/artery (p less than 0.05); cHyp completely prevented this increase since collagen was 1.0 +/- 0.2 mg/artery (p less than 0.05). Hypoxia increased elastin from 1.1 +/- 0.1 to 2.4 +/- 0.2 mg/artery (p less than 0.05); cHyp had no apparent effect since elastin was 2.1 +/- 0.1 mg/artery. Also, cHyp did not affect RVP or vascular collagen or elastin in air-breathing animals. The cHyp treatment prevented luminal narrowing and thickening of arteriolar walls by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001160:Arterioles / Q000473:pathology; D002302:Cardiac Output; D002908:Chronic Disease; D003094:Collagen / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006352:Heart Ventricles; D006400:Hematocrit; D006909:Hydroxyproline / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D003094:Collagen; D006909:Hydroxyproline