Angiotensin receptor subtype 1 mediates angiotensin II enhancement of isoproterenol-induced cyclic AMP production in preglomerular microvascular smooth muscle cells

In a previous study, we found that angiotensin (Ang) II enhances beta-adren oceptor-induced cAMP production in cultured preglomerular microvascular smo oth muscle cells (PMVSMCs) obtained from spontaneously hypertensive rats. T he purpose of the present investigation was to identify the Ang receptor su btypes that mediate this effect. In our first study, we compared the abilit y of Ang II, Ang III, Ang (3-8), and Ang (1-7) to increase cAMP production in isoproterenol (1 mu M)-treated PMVSMCs. Each peptide was tested at 0.1, 1, 10, 100, and 1000 nM. Both Ang II and Ang III increased intracellular (E C(50)s, 1 and 11 nM, respectively) and extracellular (EC(50)s, 2 and 14 nM, respectively) cAMP levels in a concentration-dependent fashion. In contras t, Ang (3-8) and Ang (1-7) did not enhance either intracellular or extracel lular cAMP levels at any concentration tested. In our second study, we exam ined the ability of L 158809 [a selective Ang receptor subtype 1 (AT(1)) re ceptor antagonist] to inhibit Ang II (100 nM) and Ang III (100 nM) enhancem ent of isoproterenot (1 mu M)-induced cAMP production in PMVSMCs. L 158809 (10 nM) abolished or nearly abolished (p < .001) Ang II and Ang III enhance ment of isoproterenol-induced intracellular and extracellular cAMP levels. In contrast, PD 123319 (300 nM; a selective AT(2) receptor antagonist) did not significantly alter Ang II enhancement of isoproterenol-induced intrace llular or extracellular cAMP levels. We conclude that AT(1) receptors, but not AT(2), Ang (3-8), nor Ang (1-7) receptors mediate Ang II and Ang III en hancement of beta-adrenoceptor-induced cAMP production in cultured PMVSMCs.