DILATORY EFFECT OF FUROSEMIDE ON RAT TRACHEAL ARTERIOLES AND VENULES

Furosemide pretreatment greatly reduces the severity of an asthmatic r esponse to several types of bronchoconstrictor challenge. Indirect evi dence suggests that furosemide exerts its protective effects by dilati ng the airway vasculature during thermal stress. To test the hypothesi s that furosemide dilates airway microvessels, the tracheas of anesthe tized rats were surgically exposed and continuously suffused with Kreb s Ringer bicarbonate warmed to 37 degrees C. Tracheal adventitial arte rioles (13.0 to 41.0 mu m initial diameter, n = 47) and venules (50.0 to 99.0 mu m initial diameter, n = 46) were visualized with a videomic roscope, and vessel diameters were measured using videocalipers. When vessels were preconstricted with 10(-4) M phenylephrine, a selective a lpha(1)-adrenergic agonist, and then treated with 10(-4) M furosemide, significant (p < 0.05) dilation was observed in both arterioles (from 64.6 to 79.5% of their initial diameter) and venules (from 52.1 to 65 .4% of their initial diameter). When vessels were preconstricted with 10(-4) phenylephrine, after pretreatment with the cyclooxygenase inhib itor indomethacin (5.0 mg/kg), 10(-4) M furosemide significantly dilat ed arterioles (from 77.5 to 93.0% of their initial diameter) and venul es (from 58.5 to 80.1% of their initial diameter). In vessels preconst ricted with 10(-3) M L-NAME, an inhibitor of nitric oxide synthesis, a ddition of 10(-4) M furosemide to the suffusion still caused significa nt dilation in arterioles, from 77.4 to 88.8% of their initial diamete r, and in venules from 79.5 to 86.7% of their initial diameter. These data confirm that furosemide, when applied topically, dilates tracheal arterioles and venules by cyclooxygenase-and nitric oxide-independent mechanisms.