The possibility of an impaired hepatic de‐esterification of enalapril to enalaprilat due to hepatic dysfunction was assessed in seven patients with compensated liver cirrhosis and 10 normal control subjects. The peak serum concentration and time to the peak serum concentration of enalaprilat, as well as the suppression of serum angiotensin converting enzyme activity, following a single oral dose of enalapril maleate (10 mg) were not different in the two groups. The elimination half‐life of enalaprilat was related to renal function. The results suggest that hepatic biotransformation of the drug may not be disturbed in a clinically significant manner in patients with moderate hepatic dysfunction due to compensated liver cirrhosis.

A possible link between hyperinsulinaemia or insulin resistance and hypertension is currently debated. Recent evidence suggests that patients with essential hypertension are insulin resistant'2 and that hyperinsulinaemia is associated with raised blood pressure in subjects with normal glucose tolerance.3 Insulin enhances sodium reabsorption from the renal tubules and stimulates the activity of the sympathetic nervous system.5 Nevertheless, it is yet unknown whether hyperinsulinaemia itself is causally related to increased blood pressure or is merely the consequence of insulin resistance in hypertensive patients. This study was designed to evaluate the relation between serum insulin concentration and blood pressure in non-obese patients with insulinoma in order to study the effect of chronic hyperinsulinaemia on blood pressure. Patients, methods, and resultsWe evaluated data obtained from eight Japanese patients with insulinoma (six women and two men, mean (range) age 41 (24-56), mean (range) body mass index 22-5 (21-25) kg/m2) admitted to Hirosaki University Hospital during . The mean duration of the disease was assumed to be 34-8 (range 2-62) months, estimated from the time of appearance of the first hypoglycaemic symptom(s). The diagnosis of insulinoma was confirmed by histological examination of the resected insuloma in all patients. The renal, hepatic, and cardiac functions of the eight patients were all within normal ranges. Two patients had a familial history of hypertension and the remaining six did not. Ninety three non-obese subjects (45 women and 48 men, mean (range) age 48 (20-65), mean (range) body mass index 23-2 (18-26) kg/M2) with normal glucose tolerance, according to the World Health Organisation criteria, served as controls.We compared, firstly, the blood pressure of the patients with insulinoma with that of the controls and, secondly, blood pressure, and serum insulin and fasting plasma glucose concentrations before and after resection of the insulinoma. Blood pressure was measured in the supine position at 8 00 am and fasting Geometric mean of serum insulin and blood pressure concentrations (95% confidence interval) in eight patients with insulinoma before and after operation and controls CommentInsulin is considered to have a role as a pressor factor.45 Nevertheless, blood pressure in our patients with insulinoma, who were assumed to be sensitive to insulin, was not higher than in the controls and was not reduced after resection of the insulinoma. These results suggest that hyperinsulinaemia in patients with insulinoma is not associated with increased blood pressure. The precise reason(s) for the lack of association between serum insulin concentration and blood pressure in our patients is unclear. The period of hyperinsulinaemia in the patients with insuloma might have been too short for a change in blood pressure to develop compared with that experienced by hypertensive patients. Although the results obtained from this small number of patients need to be interpreted with caution, the obser...

To assess the relationship between blood pressure (BP) and serum insulin level in non-obese (body mass index (BMI) < or = 27 kg m-2), middle-aged (40-64 years of age) Japanese subjects with normal glucose tolerance, a three-phase study protocol was designed. First, the responses of plasma glucose and serum insulin to an oral glucose load were compared between 40 patients with untreated essential hypertension and 40 age-, sex- and BMI-matched normotensive control subjects. Second, the glucose and insulin responses to an i.v. glucose load were evaluated in 7 non-obese hypertensive, 7 non-obese normotensive and 7 obese hypertensive subjects. Third, BP and serum lipid profile were compared between 21 hyperinsulinaemic (serum insulin level (while fasting, after glucose loading, or both) > 2 SDs higher than the mean) and 21 age-, sex- and BMI-matched normoinsulinaemic subjects (serum insulin level within 1 SD of the mean). The glucose and insulin responses to the oral glucose load were comparable between the hypertensive and normotensive groups. Similarly, the glucose and insulin responses to the i.v. glucose load were comparable between the non-obese hypertensive and normotensive groups, whereas the mean AUCinsulin in the obese hypertensive group was significantly greater (p < 0.01) than that in either of the non-obese groups. The respective mean values for systolic and diastolic BPs did not differ between the hyperinsulinaemic and normoinsulinaemic groups. The mean serum triglyceride and HDL cholesterol concentrations were significantly higher (p < 0.01) and lower (p < 0.05), respectively, in the hyperinsuslinaemic than in the normoinsulinaemic group.(ABSTRACT TRUNCATED AT 250 WORDS)

We measured the urinary excretions of dopamine, noradrenaline and adrenaline, their conjugated metabolites, urinary excretion of sodium and creatinine clearance simultaneously in 21 patients with Type 2 (non-insulin-dependent) diabetes and 6 normal subjects. The mean (+/- SEM) value for urinary excretion of dopamine (52.4 +/- 8.8 micrograms/day) in diabetic patients with nephropathy (Group C, n = 12) was significantly lower (P less than 0.01) than in the normal subjects (Group A, 179.7 +/- 15.5 micrograms/day) and in diabetic patients without nephropathy (Group B, n = 9, 131.5 +/- 16.5 micrograms/day). The mean values for the urinary excretions of noradrenaline and adrenaline were also significantly lower (P less than 0.01) in Group C than in Groups A and B. In addition, the mean urinary excretion of conjugated metabolite of dopamine in Group C was significantly lower (P less than 0.05) than in Group A. There was a trend toward the observation that the mean 24-h urinary excretion of sodium in Group C (121.6 less than 12.9 mEq) was lower as compared with that in Group A (140.8 +/- 8.9 mEq) or B (150.7 +/- 17.9 mEq). A multiple regression analysis revealed that the 24-h urinary excretion of dopamine correlated significantly with creatinine clearance, systolic (P less than 0.01) and diastolic (P less than 0.05) blood pressures. The results indicate that synthesis or secretion of renal dopamine might decrease with a progression of diabetic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

The renal effects of oral maintenance doses of nicardipine 60-120 mg/day have been studied in 18 hypertensive patients with Type 2 (non-insulin-dependent) diabetes mellitus: 6 with normoalbuminuria (urinary albumin excretion rate, AER less than 20 micrograms.min-1, Group A); 6 with incipient nephropathy, (AER 20-200 micrograms.min-1, Group B); and 6 with overt nephropathy (AER greater than 200 micrograms.min-1, Group C). Treatment for 4 weeks significantly lowered the systolic and diastolic blood pressures and reduced total renal vascular resistance in all three groups. Nicardipine increased renal blood flow significantly in Group C and slightly in Group B, and had no effect in Group A. Glomerular filtration rate remained unchanged in all three groups. It significantly reduced AER and the fractional clearance of albumin in Group B, whereas AER in Groups A and C was not altered. Plasma renin activity, aldosterone concentration, osmotic pressure, serum total protein and albumin concentrations and haemoglobin A1c level were similar in the control and nicardipine phases in all three groups. The results suggest that nicardipine may preserve renal function whilst having a concomitant hypotensive action in hypertensive Type 2 diabetic patients with normoalbuminuria and incipient nephropathy, and that the drug may improve renal blood flow in patients with overt nephropathy. The effect of the drug on urinary albumin excretion may deserve further investigation.