Reduced body clearance as the major mechanism of the potentiation by β 2-adrenergic agonists of paraquat lethality in rats

Abstract

Reduced Body Clearance as the Major Mechanism of the Potentiation by β2-Adrenergic Agonists of Paraquat Lethality in Rats. Maling, H. M., Saul, W., Williams, M. A., Brown, E. A. B., and Gillette, J. R. (1978). Toxicol. Appl. Pharmacol. 43, 57–72. In rats, the potentiation of paraquat toxicity by l-isoproterenol and by preferential β2-adrenergic agonists (salbutamol, carbuterol, and fenoterol) was blocked by pretreatment with dl-propranolol. l-Propranclol and dl-propranolol were equally effective and d-propranolol was relatively ineffective. l-Isoproterenol and the β2-agonists did not increase paraquat uptake by rat lung slices in vitro. Isoproterenol treatment in vivo decreased urinary excretion of paraquat during the first 2 hr and enhanced paraquat concentrations in tissues. These increased tissue concentrations were correlated with reduced body clearances of paraquat in isoproterenol-treated rats. Isoproterenol treatment also decreased the body clearance of N-methyl nicotinamide (NMN) and p-aminohippuric acid (PAH). Since the body clearance of both acidic (PAH) and basic (NMN and paraquat) substances was decreased, it appears possible that isoproterenol caused these effects by decreasing the effective renal blood flow.