An increase in oxidative stress is implicated in the pathophysiology of left ventricular hypertrophy (LVH). Recent studies suggest that a phagocyte-type NADPH oxidase is an important source of cardiac superoxide production. We investigated the cardiac response to chronic pressure overload in gene-modified mice lacking the gp91phox subunit of NADPH oxidase and matched wild-type C57BL/6J controls. Adult male mice (16-20 g) were anaesthetised (2.5 % isofluorane) and the suprarenal abdominal aorta was constricted with an 8.0 nylon suture tied down onto a 29-gauge needle (~70 % constriction). Sham animals underwent an identical procedure with the exception of band placement. Perioperative mortality was < 10 % in both groups. Animals were studied 2 weeks later (n = 6-8 per group) and were killed humanely according to Home Office guidelines, using sodium pentobarbitone (120 mg kg^-1 I.P.). Data are expressed as means ± S.E.M. and statistical analysis was made using Student’s unpaired t test or two-way ANOVA for repeated measures, as appropriate. In all cases, P < 0.05 was taken to be significant. Aortic banding induced similar (~40 %) significant increases in LV/body weight ratio in wild-type (4.57 ± 0.29 vs. 3.21 ± 0.07 mg g^-1) and gp91phox^-/- mice (4.87 ± 0.18 vs. 3.40 ± 0.07 mg g^-1). Lung/body weight ratios were unchanged in both groups. Expression of atrial natriuretic factor mRNA (semi-quantitative PCR) was significantly increased to a similar extent in banded wild-type and gp91phox^-/- mice (1008 ± 138 and 1244 ± 250 %, respectively). However, cardiac interstitial fibrosis (Masson’s trichrome staining) was significantly increased only in wild-type bands (144 ± 33 %) but was unchanged in gp91phox^-/- bands (9 ± 28 %) compared with shams. Cardiac function was studied in isolated ejecting hearts, with measurement of high fidelity LV pressure (1.4 F Millar catheter), aortic and coronary flow. Wild-type bands showed significant systolic and diastolic dysfunction compared with shams (LV dP/dt_max: 4395 ± 123 vs. 5855 ± 249 mmHg s^-1; cardiac work: 7195 ± 648 vs. 10 950 ± 712 mmHg ml min^-1 g^-1; LV end-diastolic pressure: 19.4 ± 1.1 vs. 15.8 ± 0.9 mmHg; all P < 0.05). However, banding did not cause either LV systolic or diastolic dysfunction in gp91phox^-/- mice (e.g. LV dP/dt_max: 5504 ± 445 vs. 5584 ± 229 mmHg s^-1; LV end-diastolic pressure: 18.2 ± 1.8 vs. 19.3 ± 1.3 mmHg; P = n.s.). The development of interstitial fibrosis and LV systolic and diastolic dysfunction in chronic pressure overload are inhibited in gp91phox-null mice, despite a similar degree of LVH to wild-type bands. These results suggest that a gp91phox-containing NADPH oxidase is involved in the development of both contractile dysfunction and interstitial fibrosis but not hypertrophy per se during chronic pressure overload.

All procedures accord with current UK legislation.