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 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.
Miyazaki
Y
Y
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Murakami
H
H
Hirata
A
A
Fukuoka
M
M
Masuda
A
A
Ura
N
N
Shimamoto
K
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007333:Insulin Resistance; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D013841:Thiazepines / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D013841:Thiazepines; C055603:temocapril hydrochloride; D012964:Sodium