Abstract 5534: Critical Role of CuZnSOD in Regulating Renal Microcirculation and in Angiotensin II-Induced Hypertension
Superoxide (O2−), main reactive oxygen species in the vasculature, plays a major role in both renal hemodynamic and blood pressure control. O2− levels are limited by superoxide dismutase (SOD) isoforms. Their functional significance in renal and systemic hemodynamics is not clear. The role of SOD1 in afferent arteriolar responsiveness and in angiotensin II (Ang II)-induced hypertension was investigated in SOD1-deficient (SOD1-ko), SOD1-transgenic (SOD1-tg) mice and in littermate controls (wild-type). Arteriolar constrictions to Ang II (10−14–10−6 mol/l) were weaker in SOD1-tg (−14%) and stronger in SOD1-ko (−89%) compared with wild-types (−41%). Unspecific nitric oxide synthase (NOS) inhibition with Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME; 10−4 mol/l) reduced basal diameters in wild-types by −8%, in SOD1-ko by −2%, and in SOD1-tg by −38%. Simultaneous application of L-NAME and Ang II caused a similar response in all groups. SOD-mimetic (Tempol; 10−4 mol/l) had no significant effect in wild-types or SOD1-tg, but caused vasodilatation in SOD1-ko (11%). Simultaneous application of tempol and Ang II attenuated the contractile response only in SOD1-ko (−46%), compared with Ang II alone. Basal blood pressures were similar; however the hypertensive response to chronic Ang II infusion was exaggerated in SOD1-ko (27%) compared with wild-types (9%). The different SOD1-levels were not associated with changes in nitrate/nitrite (NOx) excretion or in renal mRNA expression for NOS-, NADPH oxidase-, SOD-isoforms, or Ang II receptors. In conclusion, SOD1 plays an important role in the control of afferent arteriolar tone, mainly by modulating the NO bioavailability. SOD1-deficiency aggravates Ang II-induced hypertension, which underscores the importance of oxidative stress in this model of hypertension.