Extracellular Superoxide Dismutase Is a Major Determinant of Nitric Oxide Bioavailability

Abstract

The bioavailability of nitric oxide (NO) within the vascular wall is limited by superoxide anions (O2·−). The relevance of extracellular superoxide dismutase (ecSOD) for the detoxification of vascular O2·− is unknown. We determined the involvement of ecSOD in the control of blood pressure and endothelium-dependent responses in angiotensin II–induced hypertension and renovascular hypertension induced by the two-kidney, one-clip model in wild-type mice and mice lacking the ecSOD gene. Blood pressure was identical in sham-operated ecSOD+/+ and ecSOD−/− mice. After 6 days of angiotensin II–treatment and 2 and 4 weeks after renal artery clipping, blood pressure was significantly higher in ecSOD−/− than ecSOD+/+ mice. Recombinant ecSOD selectively decreased blood pressure in hypertensive ecSOD−/− mice, whereas ecSOD had no effect in normotensive and hypertensive ecSOD+/+ mice. Compared with sham-operated ecSOD+/+ mice, sham-operated ecSOD−/− mice exhibited attenuated acetylcholine-induced relaxations. These res...