The effects of the
angiotensin converting enzyme (
ACE) inhibitor temocapril on
insulin sensitivity and its effects on renal
sodium handling and the pressor system were investigated in essential hypertensive patients (EHT). Seven EHT were hospitalized and underwent a 2-h euglycemic hyperinsulinemic
glucose clamp before and after 2 weeks' administration of
temocapril (4 mg/day).
Insulin sensitivity was calculated using the M value from the infusion rate of
glucose with
hyperinsulinemia using the
glucose clamp method. Renal clearances of
sodium,
lithium,
creatinine, and paraaminohippuric
acid were used to calculate fractional proximal and distal tubular reabsorption of
sodium (FPR(Na), FDR(Na)) and renal plasma flow (RPF) before and during
insulin infusion by the
glucose clamp method.
Temocapril decreased blood pressure and increased M value significantly. Before
temocapril treatment,
hyperinsulinemia by the
glucose clamp induced significant decreases of urinary excretion of
sodium (U(Na) V) and fractional excretion of
sodium (FENa).
After treatment, these decreases were attenuated, and the change of U(Na) V (deltaU(Na) V) with
hyperinsulinemia was significantly higher and deltaFENa showed a higher tendency, compared with before the treatment. FPR(Na) showed no change with
hyperinsulinemia before treatment, but significantly decreased
after treatment. DeltaFPR(Na) was significantly lower
after treatment than that before treatment. FDR(Na) showed an increase with
hyperinsulinemia, and deltaFDR(Na) was similar between before and
after treatment. RPF showed no change with
hyperinsulinemia, and no difference was found in deltaRPF between before and
after treatment. Plasma
norepinephrine level (PNE) and plasma
renin activity (PRA) showed increases, whereas plasma
aldosterone concentration (PAC) did not change with
hyperinsulinemia. There were no significant differences in deltaPNE, deltaPRA, and deltaPAC between before and
after treatment. From these results, it is suggested that in EHT 1)
temocapril improves
insulin resistance, and 2) although
temocapril shows no significant influence on the augmentation of pressor systems by
hyperinsulinemia, this agent attenuates the
sodium-retaining action of
hyperinsulinemia, which may be attributable to suppression of
insulin-induced
sodium reabsorption at the proximal tubules. These effects may lead to additional beneficial effects in the treatment of essential hypertensives with
insulin resistance.