Renal oxygenation defects in the spontaneously hypertensive rat:: Role of AT1 receptors

Background. The spontaneously hypertensive rat (SHR) has oxidative stress and enhanced O-2 usage () relative to tubular sodium transport (T-Na ). Angiotensin II (Ang II) acting on Type I receptors (AT(1) -R) causes renal oxidative stress and functional nitric oxide (NO) deficiency that could enhance O-2 usage. Therefore, we investigated the hypothesis that AT(1) -Rs mediate the inefficient renal oxygenation in the SHR. Methods. Groups of SHR and WKY received vehicle (Veh), candesartan (Cand) or hydralazine + hydrochlorothiazide + reserpine (HHR) for two weeks. Results. Compared to WKY + Veh, the elevated BP of SHR + Veh (153 +/- 3 vs 115 +/- 3 mm Hg; P < 0.001) was normalized by Cand (117 +/- 4) or HHR (113 +/- 5 mm Hg). The reduced renal blood flow of SHR + Veh (2.4 +/- 0.3 vs. 4.1 +/- 0.3 mL . min(-1) . 100 g(-1) ) was increased (P < 0.05) by Cand (3.6 +/- 0.3) and HHR (3.2 +/- 0.2). Compared to WKY + Veh, SHR + Veh had a 50% reduction in T-Na : (16.9 +/- 2.0 vs. 7.8 +/- 0.9 mumol: mumol(-1) , P < 0.01) that was unchanged by HHR (8.6 +/- 1.1), but was increased by Cand (13.2 +/- 1.4; P < 0.01). The pO(2) of outer cortex was lower in SHR + Veh than WKY + Veh (31 +/- 3 vs. 41 +/- 2 mm Hg; P < 0.05) and it was not changed significantly by HHR (37 +/- 2) but was normalized by Cand (44 +/- 3 mm Hg; P < 0.01). The pO(2) in the deep cortex also was lower in SHR + Veh than WKY + Veh (18 +/- 3 vs. 30 +/- 3 mm Hg; P < 0.005) and was not changed significantly by HHR (19 +/- 2), but was increased by Cand (25 +/- 3 mm Hg; P < 0.05). Conclusions. The reduced pO(2) in outer and inner cortex, and inefficient utilization of O-2 for Na+ transport in the SHR kidney can be ascribed to the effects of AT(1) -R, largely independent of blood pressure.