NON-CAMP-MEDIATED BRONCHIAL ARTERIAL VASODILATION IN RESPONSE TO INHALED BETA-AGONISTS

We studied the dose-dependent effects of inhaled isoetharine HCL, a be ta-adrenergic bronchodilator (2.5, 5.0, 10.0, and 20.0 mg), on bronchi al blood flow ((Q) over dot br) in anesthetized sheep. Isoetharine res ulted in a dose-dependent increase in (Q) over dot br. With a total do se of 17.5 mg, (Q) over dot br increased from baseline values of 22 +/ - 3.4 (SE) to 60 +/- 16 ml/min (P < 0.001), an effect independent of c hanges in cardiac output and systemic arterial pressure. To further st udy whether synthesis of endogenous nitric oxide (NO) affects p-agonis t-induced increases in (Q) over dot br, we administered isoetharine (2 0 mg) by inhalation before and after the NO-synthase inhibitor N-omega -nitro-L-arginine methyl ester (L-NAME). Intravenous L-NAME (30 mg/kg) rapidly decreased (Q) over dot br by similar to 80% of baseline, wher eas L-NAME via inhalation (10 mg/kg) resulted in a delayed and smaller (similar to 22%) decrease. Pretreatment with L-NAME via both routes o f administration attenuated bronchial arterial vasodilation after subs equent challenge with isoetharine. We conclude that isoetharine via in halation increases (Q) over dot br in a dose-dependent manner and that beta-agonist-induced relaxation of vascular smooth muscle in the bron chial vasculature is partially mediated via synthesis of NO.