title: Renal oxygenation defects in the spontaneously hypertensive rat: role of AT1 receptors.
abstract: BACKGROUND
  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.
  
  
  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 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Nephrology and Hypertension and Center for Hypertension and Renal Disease Research, Georgetown University, Washington, DC, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Welch
authors.forename: Horst
authors.initials: H
authors.lastname: Baumgärtl
authors.forename: Dietrich
authors.initials: D
authors.lastname: Lübbers
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Wilcox
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D006400:Hematocrit; D006977:Hypertension, Renal / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism
chemical_list: D044140:Receptor, Angiotensin, Type 1; D012964:Sodium; D010100:Oxygen