At2 Receptor-Mediated Vasodilation in the Heart: Effect of Myocardial Infarction.
To investigate the functional consequences of the changes in AT2 receptor density that have been reported following myocardial infarction (MI; Matsubara, Circ Res, 1998), three consecutive 10 min intravenous infusions of angiotensin (Ang) II (100, 300 and 1000 ng/kg/min) were given to 19 sham-operated and 16 coronary artery-ligated rats, at four weeks after surgery, pretreated with either saline, the AT1 receptor antagonist irbesartan (100 μg/kg/min for 30 min), or the AT2 receptor antagonist PD123319 (20 μg/kg/min for 30 min, followed by continuous infusion). Systemic and regional hemodynamic effects were studied using the radioactive microsphere method. Ang II induced comparable changes in sham and MI rats in mean arterial pressure (MAP; maximally +30±10% and +30±8%, resp., mean±SEM) and systemic vascular conductance (cardiac output/MAP, -27±8% and -32±5%, resp.). Cardiac output decreased in MI (-20±5%) but not in sham rats. Irbesartan decreased MAP by 34% (sham) and 22% (MI), increased SVC by 41% (sham) and 24% (MI), and blocked the Ang II-mediated systemic hemodynamic effects in both sham and MI rats, while PD123319 did not affect these parameters. Myocardial conductance at baseline was diminished in MI vs. sham rats (41±3 vs. 55±6 μl/min/mmHg, resp.), while renal conductance was comparable in both groups (168±9 vs. 156±18 μl/min/mmHg, resp.). Ang II increased myocardial conductance maximally to 56±3 (MI) and 72±3 (sham) μl/min/mmHg, and decreased renal conductance to 67±4 (MI) and 74±8 (sham) μl/min/mmHg. Irbesartan increased renal, but not myocardial, conductance in both groups and blocked the Ang II-mediated renal vasoconstriction. PD123319 did not affect renal or myocardial conductance and blocked the Ang II-mediated myocardial vasodilation in sham but not in MI rats. PD123319 did not affect the Ang II-mediated renal responses. In conclusion, Ang II increases myocardial, but not renal, conductance (i.e., induces vasodilation) via AT2 receptor stimulation. The inability of PD123319 to block this response in MI rats suggests either an upregulation of AT2 receptors or a role for non-AT1, non-AT2 receptors in the infarcted heart.