CHARACTERIZATION OF PD-121981-INDUCED AND CGP-42112-INDUCED UNMASKINGOF LOW CONCENTRATION EFFECTS OF ANGIOTENSIN-II IN RABBIT ABDOMINAL-AORTA

The unmasking of the low concentration effect of angiotensin II (All) was identified within the concentration ranges of 10(-13) to 10(-11) M of All by PD 121981 (5-diphenylacetyl-1 tetrahydro-1H-imidazo[4,5-c]- pyridine-6-carboxylic acid) and 10(-12) to 3 x 10(-10) M of All by CGP 42112 -alpha-benzyl-oxycarbonyl-Arg)Lys-His-Pro-lle-OH), AT(2) antago nists, in association with the ordinary contraction curve, i.e., high concentration effect (at 3 x 10(-10) 10(-6) M Of All), in the rabbit a bdominal aorta. Thus, they showed clear biphasic features of All-induc ed contraction curves. However, this was not the case for angiotensin I and angiotensin III. This PD 121981-evoked low concentration effect of All was selectively inhibited by DuP 753 (0.01-1 nM), dithiothreito l (10 and 100 mu M), pertussis toxin (50 and 300 ng/ml, for 2 hr), nif edipine (1 and 10 mu M) and 8-(diethylamino)octyl 3,4,5-trimethoxybenz oate hydrochloride (1 and 3 mu M), which suggests the receptors were t he AT(1) subtype. However, the high concentration effect of All was no t affected by these drugs within the concentration ranges used in the present studies. These myographic results were almost consistent with the features of the intracellular Ca++ changes. Thus, it was concluded that the receptors that mediate the low concentration effect of All b elong to the AT(1) subtype. However, the current study did not determi ne the mechanism by which PD 121981 and CGP 42112 evoked the up-regula tion of the AT(1) receptors.