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

Abstract

The spontaneously hypertensive rat (SHR) has oxidative stress and enhanced O2 usage (Q(O2)) relative to tubular sodium transport (TNa). Angiotensin II (Ang II) acting on Type I receptors (AT1-R) causes renal oxidative stress and functional nitric oxide (NO) deficiency that could enhance O2 usage. Therefore, we investigated the hypothesis that AT1-Rs mediate the inefficient renal oxygenation in the SHR. Groups of SHR and WKY received vehicle (Veh), candesartan (Cand) or hydralazine + hydrochlorothiazide + reserpine (HHR) for two weeks. 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 TNa: (16.9 +/- 2.0 vs. 7.8 +/- 0.9 micromol: micromol-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 pO2 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 pO2 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). The reduced pO2 in outer and inner cortex, and inefficient utilization of O2 for Na+ transport in the SHR kidney can be ascribed to the effects of AT1-R, largely independent of blood pressure.