Is Chronic Elevation of Plasma Endothelin Levels a Cause of Hypertension?

Endothelin (ET) has been postulated to be hypertensinogenic through its potent and long-lasting vasoconstriction. Whether sustained increase in plasma ET levels causes hypertension remains to be clarified. We investigated the effects of chronic infusion of ET-1 on blood pressure, relevant to the plasma levels in normal Wistar rats. Synthetic ET-1 was administered intravenously using osmotic minipumps at a rate of 16μg/kg/day for 4 weeks. Systolic blood pressure, heart rate, and plasma ET-1 levels were determined before and after the infusion. After one-week infusion, both plasma ET-1 levels and systolic blood pressure were significantly higher than those in the control group. The systolic blood pressure showed a sustained elevation over a period of 2 weeks and then started to decrease gradually to the control levels, while plasma ET-1 levels remained elevated. There were no significant differences in heart rate and body weight between the ET-infusion and control groups. These results suggest that even a mild increase in plasma ET-1 levels could cause elevation of blood pressure. However, normalization of systolic blood pressure despite the sustained increase in plasma ET-1 levels after chronic infusion suggests that an increase in plasma ET-1 levels alone is not sufficient to cause chronic elevation of blood pressure in normal rats. (Hypertens Res 1993; 16: 247-251)