Effects of Isoproterenol, Diazoxide, Ethacrynic Acid, and Furosemide on Skeletal Muscle Vascular Resistance

Abstract

The vasodilator properties of isoproterenol, diazoxide, ethacrynic acid, and furosemide were compared in the isolated canine gracilis muscle perfused with arterial blood at a constant rate. Isoproterenol was the most potent agent with a steep vasodilator response to 10⁻⁸–10⁻⁶ M infusions and a maximal decrease in perfusion pressure of 45.5 ± 2.9% at the 10⁻⁶ M concentration. The dose – vasodilator responses for diazoxide and ethacrynic acid were parallel to that for isoproterenol but shifted three log doses to the right. The dose–response for furosemide was almost flat with a maximal vasodilator response of 15.5 ± 2.3% at the 10⁻² M concentration. The maximal effect of isoproterenol was noted within 5 min of starting the infusion whereas for diazoxide and furosemide it was noted after 10 min and for ethacrynic acid after 20 min. The mean ratio of venous to arterial resistance was unaltered during isoproterenol infusions, decreased with 10⁻³ M diazoxide, and increased with 10⁻³ M ethacrynic acid; however, none of these changes were statistically significant. Capillary hydrostatic pressure was significantly decreased only with higher concentrations of isoproterenol and diazoxide, an average of 6 mm Hg with 10⁻⁷ M isoproterenol, 8 mm Hg with 10⁻⁶ M isoproterenol, and 9 mm Hg with 10⁻³ M diazoxide. No significant changes in capillary pressure were noted during infusion of ethacrynic acid or furosemide. The results clearly differentiate these agents on the basis of potency, onset, and characteristics of vasodilator effect on sequential segments of a skeletal muscle vascular bed.