Non-cAMP-mediated bronchial arterial vasodilation in response to inhaled β-agonists

We studied the dose-dependent effects of inhaled isoetharine HCL, a beta-adrenergic bronchodilator (2.5, 5.0, 10.0, and 20.0 mg), on bronchial blood flow ((Q) over dot br) in anesthetized sheep. Isoetharine resulted in a dose-dependent increase in (Q) over dot br. With a total dose 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 changes in cardiac output and systemic arterial pressure. To further study whether synthesis of endogenous nitric oxide (NO) affects p-agonist-induced increases in (Q) over dot br, we administered isoetharine (20 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, whereas L-NAME via inhalation (10 mg/kg) resulted in a delayed and smaller (similar to 22%) decrease. Pretreatment with L-NAME via both routes of administration attenuated bronchial arterial vasodilation after subsequent challenge with isoetharine. We conclude that isoetharine via inhalation increases (Q) over dot br in a dose-dependent manner and that beta-agonist-induced relaxation of vascular smooth muscle in the bronchial vasculature is partially mediated via synthesis of NO.