STIMULATION OF ANGIOTENSIN-II AT(1) RECEPTORS IN RAT MEDIAN-EMINENCE INCREASES PHOSPHOINOSITIDE HYDROLYSIS

The aim of our study was to determine the second messenger systems for angiotensin II in the rat median eminence. Angiotensin II AT(1) recep tors are highly expressed in the median eminence and binding is select ively inhibited by the guanine nucleotide GTP gamma S, indicating poss ible coupling to G-proteins. In male rats, angiotensin II increased ph osphatidylinositol hydrolysis about 45% over basal values, with an EC( 50) Of about 2.7 nM. This effect was antagonized by 10 mu M losartan, the selective AT(1) antagonist, but not by the AT(2) competitor PD 123 319. Conversely, angiotensin II, 1 mu M, did not alter basal or forsko lin-stimulated cAMP production, and failed to influence cGMP productio n. These results support a role for angiotensin II, through stimulatio n of AT(1) receptors and increased phosphatidylinositol hydrolysis, in the median eminence. Angiotensin II increased the phosphatidylinosito l hydrolysis not only in male rats but also in ovariectomized rats, wi th or without estrogen-progesterone replacement. However, angiotensin II (up to 1 mu M) failed to increase the phosphatidylinositol hydrolys is in randomly selected intact female rats. Estrogen treatment did not alter the number or affinity of median eminence AT(1) receptors in ov ariectomized rats. The increase in phosphatidylinositol hydrolysis res ulting from stimulation of median eminence AT(1) receptors appears to be sexually dimorphic, but hormonal manipulations failed to point to a role for reproductive hormones in this phenomenon.