sodium-propionate and Hypertension

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.

Topics: Animals; Bezafibrate; Blood Glucose; Blood Platelets; Blood Pressure; Calcium; Chromans; Diet; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Fructose; Hydrogen-Ion Concentration; Hyperinsulinism; Hypertension; Hypertriglyceridemia; Hypolipidemic Agents; Insulin; Male; Propionates; Rats; Sodium-Hydrogen Exchangers; Thiazoles; Thiazolidinediones; Triglycerides; Troglitazone; Vasodilator Agents

To determine whether sex influences the rate of sodium-proton (Na+-H+)-exchange-dependent swelling of platelets from patients with essential hypertension and normotensive controls.. Platelet swelling was detected by measuring the change in optical density of platelet suspensions added to sodium propionate buffer, pH 6.7, at 37 degrees C. We studied 56 subjects, 28 men and 28 women, each group containing 14 normotensive and 14 hypertensive subjects. The groups were well matched for sex, ethnicity and age.. That platelet swelling was dependent on Na+-H+ exchange was demonstrated by performing blockade by 5-(N,N-hexamethylene)-amiloride and by measuring its dependence on extracellular Na+ concentration. The rate of swelling of platelets from hypertensive men [(14.2 +/- 0.9) x 10(-3)/s] was higher than that of those from normotensive men [(10.1 +/- 0.5) x 10(-3)/s], normotensive women [(10.0 +/- 0.5) x 10(-3)/s] and hypertensive [(11.1 +/- 0.8) x 10(-3)/s] women. The interaction between sex and hypertension was significant (P < 0.05 by analysis of variance).. Sex influences the effect of hypertension on the rate of swelling of platelets exposed to sodium propionate (pH 6.7).

Topics: Adult; Blood Platelets; Female; Humans; Hypertension; Male; Middle Aged; Propionates; Reference Values; Sex Characteristics; Sodium-Hydrogen Exchangers

Using a Coulter-based cell sizing method, we have previously demonstrated that, in response to cytoplasmic acidification by 140 mmol/l sodium propionate, both the mean initial rate of amiloride-sensitive platelet volume swelling and the net volume change achieved at steady-state are greater in essential hypertensives than in normotensives. In the present study, we extend this observation by showing that, in response to graded propionate exposure (56-140 mmol/l), steady-state amiloride-sensitive volume responsiveness (as percentage increase over baseline) increases linearly, and the mean slope of the line relating amiloride-sensitive volume change and propionate concentration is increased in hypertensives (0.40 +/- 0.02 versus 0.32 +/- 0.02% per mmol/l propionate, P less than 0.003). In 56 mmol/l propionate, average amiloride-sensitive platelet swelling is significantly less in hypertensives than in normotensives (7.6 +/- 0.8 versus 11.1 +/- 0.9%, P less than 0.05), but in 140 mmol/l propionate, swelling is significantly increased in hypertensives (40.8 +/- 1.7 versus 36.2 +/- 1.5%, P less than 0.05). Since platelet intracellular calcium concentration is elevated in some hypertensives and Ca2+ is known to stimulate Na(+)-H+ antiport, the transport system that is the primary determinant of amiloride-sensitive cell swelling during propionate incubation, we studied the effects of the Ca2+ ionophore, ionomycin, on volume regulation. In both normotensives and hypertensives, ionomycin (2 x 10(-10 to 2 x 10(-7) mol/l) causes dose-related increases in amiloride-sensitive platelet swelling during graded propionate exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Amiloride; Blood Platelets; Calcium; Carrier Proteins; Female; Humans; Hydrogen-Ion Concentration; Hypertension; Ionomycin; Male; Propionates; Sodium-Hydrogen Exchangers