Effects of continuous adenosine infusion on pulmonary hypertension in chronically hypoxic rats / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effects of continuous subcutaneous adenosine infusion on pulmonary hypertension in chronically hypoxic rats.</p><p><b>METHODS</b>Twenty-four SD rats were randomized into normoxic group, hypoxic group and adenosine-treated hypoxic group. Hypoxic environment was simulated in a chamber filled with 10% oxygen and 90% nitrogen. After 7 days of hypoxia, adenosine were administered subcutaneously in the rats in adenosine-treated group at the rate of 100 microg kg(-1) min(-1) via an Alzet micro-osmotic pump for 14 days, while the pumps in the other two groups contained normal saline. After 21 days of hypoxia, pulmonary artery pressure and tail-cuff blood pressure were measured, with the plasma rennin activity (RA), angiotensin II (AngII), endothelin (ET)-1, and nitric oxide (NO) determined. Inducible nitric oxide synthase (iNOS) expression in the pulmonary artery of the rats was detected using immunohistochemical method.</p><p><b>RESULTS</b>The mean pulmonary artery pressure (mPAP) was significantly higher in the hypoxic group than that in the normoxic group (P<0.01) and in the adenosine-treated group (P<0.01). Plasma ET-1 was significantly higher but plasma NO significantly lower in the hypoxic group than in the normoxic group (P<0.01) and the adenosine-treated group (P<0.01). iNOS expression in the pulmonary artery was higher in the hypoxic group than in normoxic group (P<0.01), and adenosine significantly increased iNOS expression in comparison with the normoxic and hypoxic groups (P<0.01). Plasma RA and AngII in the hypoxic group were significantly higher than those in the normoxic group (P<0.01) and the adenosine-treated (P<0.01).</p><p><b>CONCLUSION</b>Adenosine administered by continuous subcutaneous infusion alleviates chronically hypoxia-induced pulmonary hypertension in rats, in which rennin angiotensin system, ET-1, and iNOS/NO play a role.</p>