The effects of acute hypoxia on central hemodynamics, regional blood flow, and regional oxygen supply (blood flow x arterial O2 concentration) were studied in conscious resting rats. Regional blood flow was determined by the radiolabeled microsphere technique. Blood pressure, heart rate; and aortic blood flow increased and total peripheral resistance decreased significantly during hypoxia. Blood flow to brain, respiratory muscles, and liver increased both in absolute value and as a fraction of the aortic blood flow. Fractional blood flow to the gastrointestinal tract, spleen, pancreas, skin, fat, and hindlimb bones decreased during hypoxia; blood flow decreased in absolute values only in stomach and fat. Oxygen supply to brain, respiratory muscles, and liver increased during hypoxia, whereas it decreased in the remaining organs investigated.
Pulmonary arterial hypertension (PAH) is prevalent in patients with obstructive sleep apnea syndrome (OSAS). Aging induces arginase activation and reduces nitric oxide (NO) production in the arteries. Intermittent hypoxia (IH), conferred by cycles of brief hypoxia and normoxia, contributes to OSAS pathogenesis. Here, we studied the role of arginase and aging in the pathogenesis of PAH in adult (9-mo-old) and young (2-mo-old) male Sprague-Dawley rats subjected to IH or normoxia for 4 weeks and analyzed them with a pressure-volume catheter inserted into the right ventricle (RV) and by pulsed Doppler echocardiography. Western blot analysis was conducted on arginase, NO synthase isoforms, and nitrotyrosine. IH induced PAH, as shown by increased RV systolic pressure and RV hypertrophy, in adult rats but not in young rats. IH increased expression levels of arginase I and II proteins in the adult rats. IH also increased arginase I expression in the pulmonary artery endothelium and arginase II in the pulmonary artery adventitia. Furthermore, IH reduced pulmonary levels of nitrate and nitrite but increased nitrotyrosine levels in adult rats. An arginase inhibitor (N(ω)-hydroxy-nor-1-arginine) prevented IH-induced PAH and normalized nitrite and nitrate levels in adult rats. IH induced arginase up-regulation and PAH in adult rats, but not in young rats, through reduced NO production. Our findings suggest that arginase inhibition prevents or reverses PAH.
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