enalapril and Glucose-Intolerance

Achievement of target blood pressure (BP) levels in subjects with metabolic syndrome (MS) by the method of stepwise antihypertensive therapy and assessment of metabolic effects of combination of spirapril and nifedipine retard.. Patients (n=20, 12 women, 8 men, mean age 54+/-3 years) with MS were first given spirapril (6 mg/day). Nifedipine retard (40 mg/day) was added if target BP was not achieved after 4 weeks. Study duration was 12 weeks. The following parameters were measured at baseline and at study end: heart rate, blood pressure, body mass, waist circumference, parameters of lipid spectrum, content of insulin including index HOMA IR, blood glucose (fasting and during oral glucose tolerance test).. Target BP levels were achieved in 18 patients (90%)--in 11 with moexipril monotherapy, in 9--after addition of nifedipine. Lowering of systolic and diastolic BP from baseline was 11 and 14%, respectively. After 3 months of combination antihypertensive therapy triglyceride levels decreased by 28% while high density lipoprotein cholesterol (CH) increased 6%. Total, low density lipoprotein CH and coefficient of atherogenecity did not change as well as fasting blood glucose after fast and oral glucose tolerance test. Concentration of fasting immunoreactive insulin significantly decreased by 34% entailing 35% decrease of insulin resistance. Therapy was well tolerated, side effects were transitory and did not cause withdrawal of treatment.. In patients with MS and mild hypertension monotherapy with spirapril and combination of spirapril with nifedipine retard caused lowering of BP to target level in 55 and 90%, respectively. Combination of spirapril and nifedipine retard exerts positive metabolic action.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cholesterol, LDL; Drug Therapy, Combination; Enalapril; Female; Glucose Intolerance; Humans; Hypertension; Male; Metabolic Syndrome; Middle Aged; Nifedipine; Severity of Illness Index

Circulating soluble E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1) concentrations were evaluated in 93 nonobese essential hypertensive patients, of whom 16 had impaired glucose tolerance and hyperlipidemia (group I); 25 had impaired glucose tolerance (group II); 28 had hyperlipidemia (group III); and 24 had no metabolic abnormalities (group IV). A group of 22 healthy volunteers served as a control group. All groups were without clinical or ultrasound evidence of vascular lesion and were matched for age, sex, and BMI. Endothelial soluble adhesion molecules were measured at baseline, during an oral glucose tolerance test, and after 12 weeks of either enalapril or placebo treatments. Plasma soluble E-selectin, ICAM-1, and VCAM-1 were higher (P < 0.05) in group I and II than in the other groups (group I: E-selectin, 96.1+/-27.1; ICAM-1, 304.0+/-102.1; VCAM-1, 626.1+/-156.2 microg/l. Group II: E-selectin, 88.0+/-18.0; ICAM-1, 268.0+/-84.1; VCAM-1, 594.1+/-140.9 microg/I. Group III: E-selectin, 70.1+/-18.1; ICAM-1, 195.1+/-68.0; VCAM-1, 495.9+/-110.1 microg/l. Group IV: E-selectin, 65.1+/-16.1; ICAM-1, 168.1+/-64.0; VCAM-1, 472.1+/-108.2 microg/l). Soluble adhesins levels were not higher than normal in groups III and IV. Plasma soluble ICAM-1 concentrations increased in group I after glucose administration and were directly correlated with 2-h insulin levels (r=0.648, P=0.007). Compared with placebo, 12 weeks of enalapril treatment significantly (P < 0.0001) reduced soluble E-selectin, ICAM-1, and VCAM-1. Decrements of soluble adhesins were not dependent on enalapril-related blood pressure changes. Therefore, an early endothelial activation was present in essential hypertensive patients with impaired glucose tolerance, regardless of the presence of hyperlipidemia. ACE inhibition counteracted such endothelial activation.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Drug Therapy, Combination; E-Selectin; Enalapril; Endothelium, Vascular; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertension; Intercellular Adhesion Molecule-1; Male; Solubility; Vascular Cell Adhesion Molecule-1; von Willebrand Factor

Recent studies indicate that the coexistence of hypertension and glucose intolerance leads to impairment in saline volume-induced diuresis and natriuresis. Furthermore, taurine and enalapril affect renal function and blood pressure (BP). Therefore, we tested the hypothesis that therapy combining taurine and enalapril would confer greater antihypertensive activity and responsiveness to saline volume loading in the hypertensive glucose-intolerant (HGI) rat than either agent alone.. Hypertensive (H) and HGI rats were treated from 6 weeks to 6 months with tap water containing no addition, taurine (0.25%), enalapril (15 mg/kg/day), or the taurine-enalapril combination. Hemodynamic and renal responses to an intravenous isotonic saline volume load were then determined in the conscious animal.. The vehicle-treated HGI rats displayed reduced saline volume-induced diuresis and natriuresis relative to their H counterparts. Although none of the three drug regimens affected BP, they were similarly effective in increasing the renal excretory responses to saline volume loading and in eliminating differences that existed between the untreated H and HGI groups. Although reduced tubular reabsorption activity contributed to the taurine- and enalapril-mediated augmentation in renal excretory function, enalapril also enhanced glomerular function. The augmentation in the glomerular filtration rate was greatest in the HGI rat treated with the combination of taurine and enalapril. Furthermore, all three drug regimens significantly reduced protein excretion in both H and HGI rats.. Despite exerting no influence on BP, all three drug regimens were renoprotective, as indicated by the drug-mediated improvement in kidney function of the HGI rat.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Animals, Newborn; Antihypertensive Agents; Body Weight; Diabetes Mellitus, Experimental; Enalapril; Glomerular Filtration Rate; Glucose Intolerance; Glucose Tolerance Test; Hemodynamics; Hypertension; Hypertension, Renal; Kidney; Kidney Function Tests; Male; Organ Size; Rats; Rats, Inbred WKY; Sodium; Taurine