The effect of systemic beta-2 adrenergic agonist therapy on the pulmonary hypertensive response to chronic hypoxia in rats.
Chronic hypoxia produces polycythemia, pulmonary hypertension, muscularization of peripheral pulmonary arteries, and right ventricular hypertrophy. The present study was designed to investigate the effects of systemic administration of a beta-2 adrenergic agonist on these responses. Male Wistar rats (9 or more in every group) were maintained in room air or 10% oxygen for 28 days. In the first experiment, they were treated with albuterol at various doses (0.05 mg/kg, 0.1 mg/kg, 0.5 mg/kg) twice during exposure to intermittent hypoxia (10 h/day). In the second experiment, rats were treated with albuterol 2.5 mg/kg subcutaneously twice daily during continuous hypoxia. Control animals in normoxia and hypoxia received 0.1 ml saline at equivalent times. All hypoxic groups developed polycythemia, significantly increased right ventricular systolic pressure, and right ventricular hypertrophy. At doses of albuterol that did not produce cardiac hypertrophy in normoxia, treatment had no effect on the development of right ventricular hypertrophy. With lower doses of albuterol in hypoxia, there was a trend towards an increase in hematocrit, but overall this did not reach significance. Treatment with high dose albuterol in continuous hypoxia significantly increased the hematocrit and enhanced the remodeling of the pulmonary vasculature (Hematocrit: saline-treated, 57.7 SEM 1.9; albuterol-treated, 63.4 SEM 1.7; p less than 0.05. Percentage of thick-walled peripheral vessels: saline-treated, 19.4 SEM 0.60; albuterol-treated, 22.7 SEM 0.85; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000420:Albuterol / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D001809:Blood Viscosity; D006332:Cardiomegaly / Q000209:etiology; D006400:Hematocrit; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000517:prevention & control*; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011086:Polycythemia / Q000209:etiology; D051381:Rats; D011919:Rats, Inbred Strains
D000318:Adrenergic beta-Agonists; D000420:Albuterol