A comparison of AT1 angiotensin II antagonists at pre- and postjunctional angiotensin II receptors of the rat tail artery.

A comparison was made of the influence of candesartan, ZD7155, losartan and eprosartan on angiotensin II effects at pre- and postjunctional AT(1) receptors of the rat tail artery. To study the anti-angiotensin II effect at prejunctional receptors, the tissues were preincubated with [(3)H]noradrenaline and then superfused and electrically stimulated (1 Hz, 2 ms, 50 mA, during 5 min); to study the angiotensin II effect at postjunctional receptors, non-cumulative concentration-response curves to angiotensin II were determined in the absence and in the presence of the antagonist. p A(2) values were calculated for competitive antagonists and p D'(2) values for insurmountable antagonists. At the prejunctional level, losartan and eprosartan displayed competitive antagonism with p A(2) values of 6.50 and 8.08, respectively, whereas candesartan and ZD7155 displayed non-competitive antagonism with p D'(2) values of 8.71 and 7.98, respectively. At the postjunctional level, the four antagonists displayed the same kind of antagonism as prejunctionally with p A(2) values for losartan and eprosartan of 8.52 and 8.22, respectively, and p D'(2) values of 10.62 and 9.01, for candesartan and ZD7155, respectively. The ratios between post- and prejunctional potencies were: losartan 101, candesartan 81, ZD7155 11, and eprosartan 1.4. We conclude that, at least functionally, pre- and postjunctional angiotensin II AT(1) receptors are different and propose that the prejunctional receptors in this tissue belong to the AT(1B)-subtype.