Chronic Effects of Intracerebroventricular Endothelin-1 on Blood Pressure and Water and Sodium Handling in the Rat.

We examined the chronic effects of Intracerebroventricular (ICY) endothelin on blood pressure (BP) and water and sodium metabolism in rats. Endothelin-1 (ET-1) at doses of 10, 30, 100ng/h or artificial cerebrospinal fluid (CSF) at a dose of 1μl/h was administered continuously into the lateral ventricle for 7 days (n=6 each). Intravenous (IV) administration of either ET-1 (100ng/h) or saline (control) was additionally done in two other groups of rats. The highest dose of ICV ET-1 produced a mild but significant increase in systolic BP on days 6 and 7 (from 125±3 to 138±5mmHg, m±SE). It transiently increased urine volume on day 1 and day 2, and sodium excretion on day 1 without stimulating water intake. These changes were not produced by the lower doses of ICY ET-1 or ICV artificial CSF. The same dose of IV ET-1 (100ng/h) also failed to produce these effects. On day 7, the pressor effect of the highest dose of ICV ET-1 was confirmed by direct BP measurement in conscious rats. Plasma norepinephrine level was significantly higher in the ICV ET-1 (100ng/h) group than the control group (384±61 vs. 222 ±40pg/ml, p<0.05), while plasma vasopressin was similar in the two groups. Depressor response to intravenous hexamethonium (20mg/kg) was significantly greater in the ICV ET-1 group than the control group. These results suggest that chronic ICV ET-1 elevates BP mainly due to activation of the sympathetic nervous system. Endothelin may also act on the brain to increase water and sodium excretion without stimulating water intake. (Hypertens Res 1994; 17: 23-28)