Troglitazone Reduces Activity of the Na⁺/H⁺ Exchanger in Fructose-Fed Borderline Hypertensive Rats

Abstract

Activation of the Na⁺/H⁺ exchanger (NHE) is known to be related to elevated blood pressure in hyperinsulinemia. We previously demonstrated that a fructose-enriched diet induced hyperinsulinemia and hypertriglyceridemia, elevated NHE activity, increased intracellular calcium concentrations ([Ca²⁺]_i), and increased blood pressure in borderline hypertensive rats (BHR). This study examines whether pharmacologically reducing plasma triglyceride or insulin concentrations lowers blood pressure and reduces NHE activity in fructose-fed BHR. Eicosapentaenoic acid (EPA), bezafibrate (BEZ), and troglitazone (TRO) were administered to treat hypertriglyceridemia and/or hyperinsulinemia. Rats were fed a 60% fructose diet or a control diet for 4 weeks, followed by a diet with either vehicle, EPA, BEZ, or TRO for 4 weeks. Intracellular pH (pHi) was measured in platelets by fluorescent dye. Platelet NHE activity was evaluated by the recovery of pHi following addition of sodium propionate (Vmax). [Ca²⁺]_i in platelets were measured fluorometrically. In fructose-fed rats, EPA prevented further increase in blood pressure, and reduced triglyceride concentration and [Ca²⁺]_i without affecting Vmax or plasma insulin concentrations. BEZ reduced triglyceride concentrations without affecting blood pressure, Vmax, [Ca²⁺]_i, or insulin concentrations. TRO prevented an increase in blood pressure, and reduced Vmax, [Ca²⁺]_i, and insulin, but not triglycerides. Plasma insulin and Vmax were positively correlated. In conclusion, improvement of hyperinsulinemia can decrease NHE activity and blood pressure in fructose-fed BHR. (Hypertens Res 2003; 26: 111-116)