Troglitazone reduces activity of the Na+/H+ exchanger in fructose-fed borderline hypertensive rats.
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.
Fujioka
Yoshio
Y
Department of Internal Medicine, Cardiovascular Division, Hyogo College of Medicine, Nishinomiya, Japan. yfujioka@hyo-med.ac.jp
Masai
Miho
M
Tsuboi
Sayaka
S
Okumura
Takahiro
T
Morimoto
Shinji
S
Tsujino
Takeshi
T
Ohyanagi
Mitsumasa
M
Iwasaki
Tadaaki
T
D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology*; D004032:Diet; D015118:Eicosapentaenoic Acid; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005632:Fructose / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D006946:Hyperinsulinism / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism*; D015228:Hypertriglyceridemia / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008297:Male; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014280:Triglycerides / Q000097:blood; D000077288:Troglitazone; D014665:Vasodilator Agents / Q000494:pharmacology*
D001786:Blood Glucose; D002839:Chromans; D005231:Fatty Acids, Unsaturated; D000960:Hypolipidemic Agents; D007328:Insulin; D011422:Propionates; D017923:Sodium-Hydrogen Exchangers; D013844:Thiazoles; D045162:Thiazolidinediones; D014280:Triglycerides; D014665:Vasodilator Agents; D005632:Fructose; D015118:Eicosapentaenoic Acid; C514135:sodium propionate; D000077288:Troglitazone; C029658:propionic acid; D002118:Calcium; D001629:Bezafibrate