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Effect of ionophore RO 2-2985 on the contractile response of canine coronary, renal and femoral arteries.

The effects of the ionophore, RO 2-2985 (X537A, RO) were studied on isolated coronary, renal and femoral arteries in two types of experiments: (1) the effect of RO as a modulator of various contractile effects of KCl and phenylephrine (PE), and (2) the effect of RO itself as a contractile agonist. The effect of the ionophore A23187 was observed in similar experiments to help determine the nature of the RO response. In the first type of experiment, RO was found to have a differential effect upon the arteries contracted with KCl. The coronary arteries relaxed upon addition of the ionophore, whereas, the femoral and renal arteries did not. A23187 had only a transient effect on KCl-contracted coronary arteries. RO relaxed femoral and renal arteries contracted with PE, and A23187 had only a transient effect. RO attenuated ED50 values and maximum tension developments to both KCl and PE, and A23187 had no effect on these parameters. In the second type of experiment, RO (only at 10-5 M) was found to contract femoral and coronary arteries, but had no effect on renal arteries. Experiments with alpha-blocking agents and calculations using association constants of RO for catecholamines suggest that RO is not acting via catecholamine chelation. The dissimilarity between the effects of RO and A23187 suggest that RO may not be working through a specific effect on Ca++. These differential responses to RO suggest variations in intervessel regulation of PE- AND KCl-induced contradictions and can explain, in part, the in vivo effects of RO on regional blood flow.