Normalization of Blood Pressure and Renal Vascular Resistance in SHR With a Membrane-Permeable Superoxide Dismutase Mimetic

Abstract

Abstract —Superoxide radical (O ₂ ⁻ ) is increased in the vessel wall of spontaneously hypertensive rats (SHR) where its blockade potentiates endothelium-dependent vasodilation. The purpose of this study was to determine the role of O ₂ ⁻ in the hypertension and renal vasoconstriction of SHR and its interaction with nitric oxide (NO). Baseline mean arterial pressure (MAP) and renal vascular resistance were markedly elevated in SHR (n=6) compared with Wistar-Kyoto rats (WKY; n=6) (145±4 versus 118±4 mm Hg, P −1 · min ⁻¹ , respectively; P −1 · min ⁻¹ ) of SHR. The MAP of SHR was more sensitive and responsive to graded infusions of tempol (0, 1.8, 18, 180, and 1800 μmol · kg ⁻¹ · h ⁻¹ IV) than that of WKY. To determine whether O ₂ ⁻ increases MAP by inactivation of NO, its synthesis was blocked in SHR with N ^w -nitro- l -arginine methyl ester (L-NAME, 11 μmol · kg ⁻¹ · min ⁻¹ IV, n=6). Whereas tempol alone significantly reduced MAP by 32% (184±12 to 121±18 mm Hg, P P −1 · min ⁻¹ IV, n=6). Finally, to determine the longer-term effect of O ₂ ⁻ , tempol (1.5 mmol · kg ⁻¹ · d ⁻¹ IP) was given for 7 days. Tempol had no effect on MAP in WKY (96±1 to 97±1 mm Hg, n=7) but significantly decreased MAP in SHR (133±2 to 120±3 mm Hg, P 2 ⁻ in the hypertension of SHR in vivo. The antihypertensive action of tempol depends on NO synthesis presumably because O ₂ ⁻ inactivates NO and thus diminishes its vasodilatory actions.