Effects of endothelin upon blood pressure in normotensive rabbits and in perinephritis hypertension

Abstract

The effects of endothelin upon blood pressure were investigated in normotensive and hypertensive rabbits. Endothelin was injected intravenously into conscious animals and blood pressure was monitored. Groups were pretreated with vehicle, calcium antagonists, indomethacin to block prostaglandin release, or NG-nitro-L-arginine methyl ester (L-NAME) to block endothelium-derived relaxing factor (EDRF) production in order to study the mechanisms of action of endothelin in normotensive and hypertensive animals. Intravenous endothelin caused a rapid depressor response lasting less than 1 min followed by a prolonged pressor response. Calcium antagonists attenuated this pressor response. Hypertensive animals showed a greater sensitivity to calcium antagonists than normotensives. High concentrations of calcium antagonists abolished the pressor response, revealing a more prolonged depressor response lasting up to 5 min. Indomethacin pretreatment caused an apparent dose-related increase in pressor responses in all animals. L-NAME pretreatment enhanced responses in normotensives but caused no change or a decrease in these responses in hypertensive animals. Neither calcium antagonists, indomethacin or L-NAME modified the initial depressor response to endothelin. However when given together with nifedipine infusion, which abolished the pressor response, indomethacin and L-NAME decreased the duration of the depressor response. In conscious rabbits extracellular calcium influx is important in mediating pressor responses to endothelin. In normotensive rabbits endothelin apparently causes release of prostaglandin and EDRF modifying responses. In hypertensive rabbits, a role for prostaglandins but not EDRF was observed in modulating responses to endothelin. Thus, the measured response to endothelin is the sum of a number of effects, the relative importance of which may be altered in pathological conditions.