A1899 Antagonizing salt-sensitive hypertension by caffeine intake through promotion of CFTR-mediated intestinal secretion of Cl−

Objectives: The intestine plays an important part in sodium absorption. Chronic intake of caffeine has been reported to attenuate salt-sensitive hypertension through promotion of excretion of urinary sodium. We investigated if chronic consumption of caffeine antagonizes salt-sensitive hypertension through inhibition of intestinal sodium absorption. Methods: Dahl salt-sensitive rats were fed 8% NaCl chow and 0.1% caffeine in their drinking water for 2 weeks. Blood pressure and fecal sodium content were measured. The effect of caffeine on the movement of chloride ions (Cl−) in enterocytes was determined using an Ussing chamber. Results: Dahl rats treated with caffeine displayed significantly lower mean blood pressure than controls, accompanied by higher fecal sodium content. Consistently, caffeine intake decreased the fluid absorption by the intestine in the fluid-perfusion experiment. Results from the Ussing chamber experiment suggested that caffeine promoted Cl− secretion through enterocyte apical cystic fibrosis transmembrane conductance regulator (CFTR) to inhibit sodium absorption. NPPB, 5-nitro-2-(3-phenylpropylamino)-benzoic acid, an inhibitor of CFTR, blocked caffeine-induced short circuit current (ΔIsc) almost completely. Moreover, depletion of cyclic adenosine monophosphate by norepinephrine abolished the effect of caffeine on Cl− secretion completely. Blockade of calcium ion (Ca2+)-activated potassium ion (K+) channels by clotrimazole also decreased caffeine-induced ΔIsc, suggesting that K+ secretion evoked by Ca2+ release from the endoplasmic reticulum may also influence the effect of caffeine. Conclusion: Chronic consumption of caffeine can reduce sodium absorption by promoting CFTR-mediated Cl− secretion in intestine, which contributes to the anti-hypertensive effect of caffeine in salt-sensitive rats.