Effects of AT1 and AT2 angiotensin receptor antagonists in angiotensin II-infused rats

Angiotensin II (Ang II) appears to exert its contractile and growth-promoting effects through the AT(1) receptor subtype, whereas the AT(2) subtype may have growth-inhibitory and proapoptotic properties. Recently, some data have challenged this emerging concept. To clarify the role of AT(1) and AT(2) receptors, we treated Wistar rats that were infused with Ang II (120 ng/kg/min subcutaneously by osmotic minipump), with the AT(1) antagonist losartan (10 mg/kg/d in the drinking water) and the AT(2) antagonist PD123319 (30 mg/kg/d subcutaneously by osmotic minipump) for 21 days. At the end of the study, tail-cuff systolic blood pressure was 106+/-2.8 mm Hg in untreated rats and 108+/-2.0 mm Hg in rats infused with Ang II that received losartan, whereas it rose to 158+/-4.9 mm Hg in Ang II-infused rats and 158+/-3.0 mm Hg in rats infused with Ang II rats and PD123319 (the two latter groups P<.01 versus the two other groups). Heart weight, and aorta cross-section/body weight ratio were higher in Ang II-infused rats than in controls and were significantly reduced in Ang II-infused rats that received losartan (P<.05). Wire-myograph-mounted coronary, renal, mesenteric, and femoral small arteries from Ang II-infused rats and Ang II-infused rats receiving PD123319 had a greater media, media cross-section, and media/lumen ratio than vessels from untreated or Ang II-infused rats treated with losartan. These results support the concept that in Wistar normotensive rats infused for 3 weeks with angiotensin II, growth in the heart, aorta, and coronary, renal, mesenteric, and femoral small arteries is mediated by the AT(1) receptor; the results show little evidence of a role of AT(2) receptors in mediating angiotensin II effects in this experimental paradigm.