Non-steroidal anti-inflammatory drugs potentiate the vasoconstrictor effects of ouabain in the dog.

The purpose of this study was to determine whether inhibitors of prostaglandin synthesis alter the peripheral vascular effects of the cardiac glycoside, ouabain. Ouabain (35 /»g/kg) was given to 12 mongrel dogs, six of which had been pretreated 1 hour previously with the non-steroidal antiinflammatory drugs (NSAID), indomethacin or meclofenamate (6 mg/kg, iv, bolus followed by 1 mg/ min infusion). Hemodynamic variables were monitored for 30 minutes before and for 3 hours after ouabain administration. Mean arterial pressure was significantly increased in all dogs for 45 minutes after ouabain, and cardiac output was unchanged. In the animals that did not receive non-steroidal anti-inflammatory drugs, ouabain transiently (15 min) decreased renal blood flow and increased renal vascular resistance. Mesenteric blood flow was not altered by ouabain until 90 minutes, after which time it was significantly increased. In the dogs pretreated with NSAID, renal blood flow was reduced for 60 minutes after administration of ouabain. In addition, 30 minutes after ouabain, the mesenteric blood flow was reduced by 43 ± 17 ml/min from a baseline value of 192 ± 42 ml/min (P < 0.05), and this reduction persisted for the entire 3-hour observation period. Control animals that did not receive ouabain showed neither an increase in arterial pressure nor a decrease in renal or mesenteric blood flow over the period of the experiment. Thus, pretreatment with NSAID enhanced the duration of the renal vasoconstrictor effects of ouabain in the dog and converted late mesenteric vasodilation to early and persistent vasoconstriction. These data imply a potentially important role for vasodilating prostaglandins in modulating the mesenteric as well as the renal circulatory responses to ouabain. Circ Res 48: 844-850, 1981