Induction of angiotensin II subtype 2 receptor-mediated blood pressure regulation in synthetic diet-fed rats

Objective Chronic feeding of a purified synthetic diet induces renin-angiot ensin system-dependent moderate high blood pressure in normal Sprague-Dawle y rats. The present study was designed to characterize the angiotensin II ( Ang II) receptor type 2 (AT(2))-specific mechanism of blood pressure regula tion in these rats. Methods The effect of the AT(2) receptor antagonist PD123319 (PD) on blood pressure was examined in vivo in synthetic diet-fed rats. Ang Ii-dependent contraction of aortic rings prepared from the synthetic diet-fed rats was a lso investigated. Results After 8 weeks of feeding the synthetic diet, the mean arterial pres sure (MAP) was significantly elevated above levels measured in control rats (117 +/- 2 Versus 102 +/- 3 mmHg, P < 0.05). Intravenous administration of PD to conscious hypertensive rats elicited an immediate dose-dependent inc rease in MAP that was sustained for approximately 7.4 min with 3 mg/kg PD, The angiotensin converting enzyme inhibitor captopril, but not the Ang II t ype 1 receptor blocker losartan, significantly attenuated the effect of PD on blood pressure. PD did not increase the plasma level of catecholamines, The PD-dependent blood pressure increase was not observed in normotensive c ontrol rats. Aortic ring assays revealed that functional activation of the AT(2) receptor occurs only in the hypertensive rats, and this AT(2) respons e is abolished by indomethacin (5 mu mol/l) but not by N-omega-nitro-L-argi nine methyl ester (100 mu mol/l). Conclusion These results clearly demonstrate that AT(2) receptor-mediated b lood pressure regulation is functional in this experimental model of hypert ension. Furthermore, cyclooxygenase metabolites might be the key mediators for the AT(2) receptor-mediated blood pressure-lowering action. JHypertens 2000, 18:1239-1246 (C) Lippincott Williams & Wilkins.