LOSARTAN (DUP-753) BLOCKS THE NATRIURETIC, KALIURETIC AND ANTIDIURETIC EFFECT OF INTRACEREBROVENTRICULAR INJECTION OF CARBACHOL IN WATER-LOADED RATS

We determined the effect of intracerebroventricular (icv) administrati on of losartan, an angiotensin II (ANG II) subtype 1 receptor (AT1) an tagonist, on icv carbachol-induced natriuresis, kaliuresis and antidiu resis in water-loaded male Holtzman rats (250-300 g) with a cannula im planted into the lateral ventricle (LV). The rats were water loaded wi th 5% of their body weight by gavage twice, with the second gavage one hour after the first. Carbachol (2 nmol in 1 mu l) was injected icv i mmediately after the second load. When losartan (DUP-753, 50 nmol in 1 mu l) was administered icv, it was given 3 min before carbachol. Prev ious icv treatment with losartan significantly reduced the icv carbach ol-induced natriuresis (324 +/- 17 mu Eq/120 min), kaliuresis (103 +/- 15 mu Eq/120 min) and antidiuresis (13.5 +/- 2.1 ml/120 min) compared to the effects of previous icv injection of saline (Nai excretion = 4 98 +/- 22 mu Eq/120 min; K+ excretion = 167 +/- 20 mu Eq/120 min; urin e volume = 5.2 +/- 1.2 ml/120 min). These results, reported as means /- SEM for 12 rats in each group, are consistent with the hypothesis t hat AT1 subtype receptors participate in the regulation of body electr olyte balance.