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

Abstract

Carvalho, Paula, Shane R. Johnson, Nirmal B. Charan.Non-cAMP-mediated bronchial arterial vasodilation in response to inhaled β-agonists. J. Appl. Physiol. 84(1): 215–221, 1998.—We studied the dose-dependent effects of inhaled isoetharine HCl, a β-adrenergic bronchodilator (2.5, 5.0, 10.0, and 20.0 mg), on bronchial blood flow (Q˙br) in anesthetized sheep. Isoetharine resulted in a dose-dependent increase in Q˙br. With a total dose of 17.5 mg, Q˙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 β-agonist-induced increases in Q˙br, we administered isoetharine (20 mg) by inhalation before and after the NO-synthase inhibitor N ω-nitro-l-arginine methyl ester (l-NAME). Intravenous l-NAME (30 mg/kg) rapidly decreased Q˙br by ∼80% of baseline, whereas l-NAME via inhalation (10 mg/kg) resulted in a delayed and smaller (∼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˙br in a dose-dependent manner and that β-agonist-induced relaxation of vascular smooth muscle in the bronchial vasculature is partially mediated via synthesis of NO.