Dietary fructose enhances angiotensin II-stimulated Na transport via activation of PKC-α in renal proximal tubules.

Angiotensin II (ANG II) stimulates proximal nephron transport via activation of classical protein kinase C (PKC) isoforms. Acute fructose treatment stimulates PKC and dietary fructose enhances ANG II's ability to stimulate Na transport, but the mechanisms are unclear. We hypothesized that dietary fructose enhances ANG II's ability to stimulate renal proximal tubule Na reabsorption by augmenting PKC-α activation and increases in intracellular Ca. We measured total and isoform-specific PKC activity, basal and ANG II-stimulated oxygen consumption, a surrogate of Na reabsorption, and intracellular Ca in proximal tubules from rats given either 20% fructose in their drinking water (fructose group) or tap water (control group). Total PKC activity was measured by ELISA. PKC-α, PKC-β, and PKC-γ activities were assessed by measuring particulate-to-soluble ratios. Intracelluar Ca was measured using fura 2. ANG II stimulated total PKC activity by 53 ± 15% in the fructose group but not in the control group (-15 ± 11%, < 0.002). ANG II stimulated PKC-α by 0.134 ± 0.026 but not in the control group (-0.002 ± 0.020, < 0.002). ANG II increased PKC-γ activity by 0.008 ± 0.003 in the fructose group but not in the control group ( < 0.046). ANG II did not stimulate PKC-β in either group. ANG II increased Na transport by 454 ± 87 nmol·min·mg protein in fructose group, and the PKC-α/β inhibitor Gö6976 blocked this increase (-96 ± 205 nmol·min·mg protein, < 0.045). ANG II increased intracellular Ca by 148 ± 53 nM in the fructose group but only by 43 ± 10 nM in the control group ( < 0.035). The intracellular Ca chelator BAPTA blocked the ANG II-induced increase in Na transport in the fructose group. We concluded that dietary fructose enhances ANG II's ability to stimulate renal proximal tubule Na reabsorption by augmenting PKC-α activation via elevated increases in intacellular Ca.