Angiotensin II-stimulated proximal nephron superoxide production and fructose-induced salt-sensitive hypertension

Angiotensin II (Ang II) increases proximal tubule superoxide (O₂^-) production more in rats fed a 20% fructose normal-salt diet compared to rats fed a 20% glucose normal-salt diet. A 20% fructose high-salt diet (FHS) increases systolic blood pressure (SBP), whereas 20% glucose high-salt (GHS) doesn't. However, it is unclear whether FHS enhances Ang II induced oxidative stress in proximal tubules, and whether this contributes to increases in BP in this model. We hypothesized that FHS augments the ability of Ang II to stimulate superoxide production by proximal tubules, and this contributes to fructose-induced salt-sensitive hypertension. We measured SBP in male Sprague Dawley rats fed FHS and GHS, and the effects of 3 mM tempol (T) and 50 mg/kg losartan (L) for 7 days. Then we measured basal and Ang II-stimulated (3.7 x 10^-8 M) O₂^- production by proximal tubule suspensions, and the role of protein kinase C (PKC). FHS increased SBP by 27±5 mmHg (n=6; p < 0.006). GHS did not. Rats fed FHS+T and GHS+T showed no significant increases in SBP. Ang II increased O₂^- production by 11±1 relative light units (RLU)/µg protein/s in proximal tubules from FHS-fed rats (n=6; p < 0.048) but not in tubules from rats fed GHS. Ang II did not significantly stimulate O₂^- production by proximal tubules from rats fed FHS+T or FHS+L. The PKC inhibitor Gö6976 blunted Ang II-stimulated O₂^- production. Conclusion: A FHS diet enhances the sensitivity of proximal tubule O₂^- production to Ang II, and this contributes to fructose-induced salt-sensitive hypertension.