EFFECTS OF THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR TEMOCAPRIL ON INSULIN SENSITIVITY AND ITS EFFECTS ON RENAL SODIUM HANDLING AND THE PRESSOR SYSTEM IN ESSENTIAL HYPERTENSIVE PATIENTS

The effects of the angiotensin converting enzyme (ACE) inhibitor temoc april on insulin sensitivity and its effects on renal sodium handling and the presser system were investigated in essential hypertensive pat ients (EHT). Seven EHT were hospitalized and underwent a 2-h euglycemi c hyperinsulinemic glucose clamp before and after 2 weeks' administrat ion of temocapril (4 mg/day). Insulin sensitivity was calculated using the M value from the infusion rate of glucose with hyperinsulinemia u sing the glucose clamp method. Renal clearances of sodium, lithium, cr eatinine, and paraaminohippuric acid were used to calculate fractional proximal and distal tubular reabsorption of sodium (FPRNa, FDRNa) and renal plasma now (RPF) before and during insulin infusion by the gluc ose 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 o f sodium (UNaV) and fractional excretion of sodium (FENa). After treat ment, these decreases were attenuated, and the change of UNaV (Delta U NaV) with hyperinsulinemia was significantly higher and Delta FENa sho wed a higher tendency, compared with before the treatment. FPRNa showe d no change with hyperinsulinemia before treatment, but significantly decreased after treatment. Delta FPRNa was significantly lower after t reatment than that before treatment. FDRNa showed an increase with hyp erinsulinemia, and Delta FDRNa was similar between before and after tr eatment. RPF showed no change with hyperinsulinemia, and no difference was found in Delta RPF between before and after treatment. Plasma nor epinephrine level (PNE) and plasma renin activity (PRA) showed increas es, whereas plasma aldosterone concentration (PAC) did not change with hyperinsulinemia. There were no significant differences in Delta PNE, Delta PRA, and Delta PAC between before and after treatment. From the se results, it is suggested that in EHT 1) temocapril improves insulin resistance, and 2) although temocapril shows no significant influence on the augmentation of presser systems by hyperinsulinemia, this agen t attenuates the sodium-retaining action of hyperinsulinemia, which ma y be attributable to suppression of insulin-induced sodium reabsorptio n at the proximal tubules. These effects may lead to additional benefi cial effects in the treatment of essential hypertensives with insulin resistance. Am J Hypertens 1998;11:962-970 (C) 1998 American Journal o f Hypertension, Ltd.