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) receptors are highly expressed in the median eminence and binding is selectively inhibited by the guanine nucleotide GTP gamma S, indicating possible coupling to G-proteins. In male rats, angiotensin II increased phosphatidylinositol 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 123319. Conversely, angiotensin II, 1 mu M, did not alter basal or forskolin-stimulated cAMP production, and failed to influence cGMP production. These results support a role for angiotensin II, through stimulation of AT(1) receptors and increased phosphatidylinositol hydrolysis, in the median eminence. Angiotensin II increased the phosphatidylinositol hydrolysis not only in male rats but also in ovariectomized rats, with or without estrogen-progesterone replacement. However, angiotensin II (up to 1 mu M) failed to increase the phosphatidylinositol hydrolysis in randomly selected intact female rats. Estrogen treatment did not alter the number or affinity of median eminence AT(1) receptors in ovariectomized rats. The increase in phosphatidylinositol hydrolysis resulting 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.