enalapril and Metabolic-Syndrome

Arterial stiffness and blood pressure (BP) augmentation are independent predictors of cardiovascular events. In a randomized, open, parallel group study we compared the effect on these parameters of combination therapy with an ACE-inhibitor plus calcium channel blocker or thiazide diuretic in 76 hypertensive patients with metabolic syndrome uncontrolled by ACE-inhibitor monotherapy. After 4weeks run-in with enalapril (ENA, 20mg), patients were randomized to a combination therapy with lercanidipine (LER, 10-20mg) or hydrochlorothiazide (HCT, 12.5-25mg) for 24weeks. Aortic stiffness (carotid to femoral pulse wave velocity, PWV), central BP values and augmentation (augmentation index, AIx) were measured by applanation tonometry. The two groups showed similar office and central BP after run-in. Office (ENA/LER: from 149.1±4.9/94.5±1.5 to 131.7±8.1/82.2±5.3; ENA/HCT: from 150.3±4.7/94.7±2.1 to 133.1±7.1/82.8±5.3mmHg) and central BP (ENA/LER 127.4±17.1/85.2±12.1 to 120.5±13.5/80.0±9.5mmHg; ENA/HCT 121.6±13.4/79.3±9.5mmHg) were similarly reduced after 24weeks. PWV was comparable after run-in and not differently reduced by the two treatments (ENA/LER from 8.6±1.5 to 8.1±1.3m/s, p<0.05; ENA/HCT from 8.5±1.2 to 8.2±1.0m/s, p<0.05). Finally, both combinations reduced AIx, but its reduction was significantly greater (p<0.05) in ENA/LER (from 26.8±10.9 to 20.6±9.1%) than in ENA/HCT arm (from 28.2±9.0 to 24.7±8.7%). In conclusion, the combination with LER caused a similar PWV reduction as compared to HCT, but a greater reduction in AIx in hypertensive patients with metabolic syndrome not controlled by ENA alone. These results indicate a positive effect of the combination of ENA/LER on central BP augmentation, suggesting a potential additive role for cardiovascular protection.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Drug Therapy, Combination; Enalapril; Female; Humans; Hydrochlorothiazide; Hypertension; Italy; Male; Metabolic Syndrome; Middle Aged; Prospective Studies; Treatment Outcome; Vascular Stiffness

The aim of this work was the scintigraphic study of brain perfusion and the elucidation of the relationship between daily variations of arterial pressure (AP) and the results of single photon emission computed tomography (SPCT) of the brain in patients with metabolic syndrome (MS). The secondary objective was to estimate effect of combined antihypertensive therapy on cerebral circulation. 24 patients with MS underwent SPCT with 99mTc HMPOA and 24 hr AP monitoring before and 6 mo after therapy with long-acting verapamil combined with slow-release indapamide or enalapril. It was shown that all the patients suffered disturbances of regional cerebral blood flow even in the absence of focal neurological symptoms. Perfusion was especially impaired in the temporal, occipital and superior frontal lobes. The degree of the night-time fall in AP was related to the level of perfusion in the right temporal region (r = -0.5; p = 0.04) which confirms the danger of extreme AD decrease in hypertonics during sleep. Combined antihypertensive therapy has positive influence on cerebral perfusion. Verapamil plus enalapril has more pronounced effect than verapamil plus indapamide on cerebral blood flow in many brain regions.

Topics: Antihypertensive Agents; Biological Availability; Blood Pressure Monitoring, Ambulatory; Brain; Cerebrovascular Circulation; Drug Therapy, Combination; Enalapril; Female; Humans; Hypertension; Indapamide; Male; Metabolic Syndrome; Middle Aged; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Verapamil

Dipeptidyl peptidase-IV inhibitors improve glucose homeostasis in type 2 diabetics by inhibiting degradation of the incretin hormones. Dipeptidyl peptidase-IV inhibition also prevents the breakdown of the vasoconstrictor neuropeptide Y and, when angiotensin-converting enzyme (ACE) is inhibited, substance P. This study tested the hypothesis that dipeptidyl peptidase-IV inhibition would enhance the blood pressure response to acute ACE inhibition. Subjects with the metabolic syndrome were treated with 0 mg of enalapril (n=9), 5 mg of enalapril (n=8), or 10 mg enalapril (n=7) after treatment with sitagliptin (100 mg/day for 5 days and matching placebo for 5 days) in a randomized, cross-over fashion. Sitagliptin decreased serum dipeptidyl peptidase-IV activity (13.08±1.45 versus 30.28±1.76 nmol/mL/min during placebo; P≤0.001) and fasting blood glucose. Enalapril decreased ACE activity in a dose-dependent manner (P<0.001). Sitagliptin lowered blood pressure during enalapril (0 mg; P=0.02) and augmented the hypotensive response to 5 mg of enalapril (P=0.05). In contrast, sitagliptin attenuated the hypotensive response to 10 mg of enalapril (P=0.02). During sitagliptin, but not during placebo, 10 mg of enalapril significantly increased heart rate and plasma norepinephrine concentrations. There was no effect of 0 or 5 mg of enalapril on heart rate or norepinephrine after treatment with either sitagliptin or placebo. Sitagliptin enhanced the dose-dependent effect of enalapril on renal blood flow. In summary, sitagliptin lowers blood pressure during placebo or submaximal ACE inhibition; sitagliptin activates the sympathetic nervous system to diminish hypotension when ACE is maximally inhibited. This study provides the first evidence for an interactive hemodynamic effect of dipeptidyl peptidase-IV and ACE inhibition in humans.

Topics: Adult; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Enalapril; Female; Heart Rate; Hemodynamics; Humans; Insulin; Male; Metabolic Syndrome; Middle Aged; Peptidyl-Dipeptidase A; Prospective Studies; Pyrazines; Renal Circulation; Sitagliptin Phosphate; Sodium; Triazoles

The aim of the study was to obtain a comparative evaluation of antihypertensive efficacy, tolerability and influence of combine therapy on myocardium mass, diastolic function of a left ventricle, lipid and carbohydrate exchange in patients with arterial hypertension in metabolic syndrome. Out of 40 examined cases 20 patients took enalapril and long-acting nifedipin and 20 ones--enalapril and moxonidine. All examination were been performed before administration of drugs and 6 months after the therapy. The dynamics of indices of ambulatory blood pressure monitoring, echocardiography, cycle ergometry, anthropometry, lipid, carbohydrate exchange and tolerability of conducted therapy was been evaluated. The use of this combination of the drugs may be recommended to be included in the treatment of arterial hypertension within the bounds of metabolic syndrome, as in most of cases they promote an achievement of target blood pressure level, have a cardioprotective action, high tolerability and favorable metabolic profile. The combination of enalapril and long-acting nifedipin has a more evident antihypertensive activity but a therapy with enalapril and moxonidine has a positive effect on the indices of carbohydrate exchange.

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Delayed-Action Preparations; Drug Therapy, Combination; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Male; Metabolic Syndrome; Middle Aged; Nifedipine; Treatment Outcome

To study effects of two hypotensive drugs--normodipin and spirapril--on intravascular activity of platelets in patients with metabolic syndrome (MS).. Normodipin was given to 25 patients with MS for 3 months, spirapril--to 20 patients for 3 months. The effect was evaluated by changes in lipid peroxidation in plasm and platelets, antioxidant defense of liquid blood and platelets, intravascular activity of platelets.. Administration of normodipin in MS patients had a positive effect on lipid peroxidation and normalized intravascular activity of platelets. Such pronounced positive effects on lipid peroxidation of plasm and platelets as well as on intravascular activity of the latter were not registered after use of spirapril.. Optimization of platelet function in MS patients can be achieved with long-term normodipin treatment.

Topics: Adult; Amlodipine; Antihypertensive Agents; Blood Platelets; Blood Pressure; Enalapril; Female; Humans; Lipid Peroxidation; Male; Metabolic Syndrome; Middle Aged; Platelet Activation; Venous Thrombosis

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

Efficacy of combination of trimetazidine (60 mg/day) and enalapril in patients with stable effort angina and metabolic syndrome was assessed in a randomized placebo controlled study of 64 patients. Anti-ischemic activity of trimetazidine was found to be significant. It was most pronounced in patients with abnormal 24-hour blood pressure index, waist/hip circumference ratio >1.0 at the background of satisfactory clinical and laboratory compensation of type 2 diabetes.

Topics: Adult; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Drug Therapy, Combination; Electrocardiography, Ambulatory; Enalapril; Female; Follow-Up Studies; Humans; Male; Metabolic Syndrome; Middle Aged; Treatment Outcome; Trimetazidine; Vasodilator Agents

The metabolic syndrome is a cluster of risk correlates that can progress to type 2 diabetes. The present study aims to evaluate a novel molecule with a dual action against the metabolic syndrome and type 2 diabetes.. We developed and tested a novel dual modulator, RB394, which acts as a soluble epoxide hydrolase (sEH) inhibitor and a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist in rat models of the metabolic syndrome-the obese spontaneously hypertensive (SHROB) rat and the obese diabetic Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat. In SHROB rats we studied the ability of RB394 to prevent metabolic syndrome phenotypes, while in ZSF1 obese diabetic rats we compared RB394 with the ACE inhibitor enalapril in the treatment of type 2 diabetes and associated comorbid conditions. RB394 (10 mg/kg daily) and enalapril (10 mg/kg daily) were administered orally for 8 weeks.. RB394 blunted the development of hypertension, insulin resistance, hyperlipidaemia and kidney injury in SHROB rats and reduced fasting blood glucose and HbA. These findings demonstrate that a novel sHE inhibitor/PPAR-γ agonist molecule targets multiple risk factors of the metabolic syndrome and is a glucose-lowering agent with a strong ability to treat diabetic complications.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Enalapril; Enzyme Inhibitors; Epoxide Hydrolases; Fatty Liver; Glucose Tolerance Test; Hypertension; Insulin Resistance; Kidney Glomerulus; Liver Cirrhosis; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; PPAR gamma; Rats; Rats, Zucker

We have explored how enalapril affects ghrelin levels in serum and renal tissues of rats with fructose-induced MetS, using 5-week-old Wistar albino male rats weighing 220 ± 20 g. They divided into 5 groups: (i) control (CT), no fructose supplement fed on standard rat pellet and tap water for 60 days, (ii) metabolic syndrome (MetS) fed with 10% fructose for 60 days, (iii) rats after metabolic syndrome developed treated with enalapril over 30 days (MetS+E30), (iv) rats in which only enalapril was administered for 60 days (E60), and (v) MetS-treated with enalapril for 60 days (MetS+E60). Enalapril maleate was given at 20mg/kg per day by gavage. Fasting serum insulin, uric acid, triglyceride, low-density lipoprotein cholesterol and total cholesterol levels were significantly higher, and the amount of high density lipoprotein cholesterol, and acylated and desacyl ghrelin levels was significantly lower in the MetS groups. Ghrelins were significantly lower in all 3 groups, which were administered enalapril than that of MetS and the control group. Immunohistochemical staining showed that the density of ghrelin was parallel to the serum levels of the peptide. Ghrelin immunoreactivity in the kidneys was of moderate density in the distal and collecting tubules, mild density in the proximal tubule and glomeruli, whereas the density decreased in the MetS group and other enalapril-treated groups. In conclusion, ghrelin levels in MetS groups were significantly lower than control group, and thus Enalapril treatment improves components of MetS and has direct effects on serum ghrelin levels that are independent of MetS.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Glucose; Drug Evaluation, Preclinical; Enalapril; Fructose; Ghrelin; Insulin; Kidney; Male; Metabolic Syndrome; Rats, Wistar

The antihypertensive treatment in patients with metabolic syndrome is unclear. We therefore used a rat model of the metabolic syndrome and compared the effects of enalapril, an angiotensin-converting-enzyme inhibitor, with candoxatril, a neutral endopeptidase inhibitor that inhibits degradation of atrial natriuretic peptide and, in addition to lowering blood pressure, exerts metabolically beneficial activity. Ten male Sprague Dawley rats were fed regular rat chow for 5 weeks. Fifty male Sprague Dawley rats were fed a high-fructose diet for 3 weeks, followed by addition of enalapril, 10 mg/Kg/d, or candoxatril, 25, 50, or 100 mg/Kg/d, for 2 weeks. Systolic blood pressure, plasma triglyceride level, and insulin level were measured at baseline and after 3 weeks and 5 weeks. Three weeks of a high-fructose diet led to a significant increase in all metabolic parameters. Candoxatril and enalapril lowered systolic blood pressure significantly (candoxatril -10 ± 1 to -22 ± 1 mm Hg and enalapril -27 ± 2 mm Hg). High-dose candoxatril and enalapril significantly decreased plasma triglyceride levels (by 17.8% and 32.8%, respectively), but only high-dose candoxatril decreased plasma insulin levels significantly (by 25.3%). High-dose candoxatril is a metabolically favorable option for lowering blood pressure in a rat model of metabolic syndrome.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Disease Models, Animal; Enalapril; Indans; Insulin; Male; Metabolic Syndrome; Propionates; Rats; Rats, Sprague-Dawley; Triglycerides

Metabolism of arachidonic acid by cytochrome P450 (CYP) to biologically active eicosanoids has been recognized increasingly as an integral mediator in the pathogenesis of cardiovascular and metabolic disease. CYP epoxygenase-derived epoxyeicosatrienoic and dihydroxyeicosatrienoic acids (EET + DHET) and CYP ω-hydroxylase-derived 20-hydroxyeicosatetraenoic acid (20-HETE) exhibit divergent effects in the regulation of vascular tone and inflammation; thus, alterations in the functional balance between these parallel pathways in liver and kidney may contribute to the pathogenesis and progression of metabolic syndrome. However, the impact of metabolic dysfunction on CYP-mediated formation of endogenous eicosanoids has not been well characterized. Therefore, we evaluated CYP epoxygenase (EET + DHET) and ω-hydroxylase (20-HETE) metabolic activity in liver and kidney in apoE(-/-) and wild-type mice fed a high-fat diet, which promoted weight gain and increased plasma insulin levels significantly. Hepatic CYP epoxygenase metabolic activity was significantly suppressed, whereas renal CYP ω-hydroxylase metabolic activity was induced significantly in high-fat diet-fed mice regardless of genotype, resulting in a significantly higher 20-HETE/EET + DHET formation rate ratio in both tissues. Treatment with enalapril, but not metformin or losartan, reversed the suppression of hepatic CYP epoxygenase metabolic activity and induction of renal CYP ω-hydroxylase metabolic activity, thereby restoring the functional balance between the pathways. Collectively, these findings suggest that the kinin-kallikrein system and angiotensin II type 2 receptor are key regulators of hepatic and renal CYP-mediated eicosanoid metabolism in the presence of metabolic syndrome. Future studies delineating the underlying mechanisms and evaluating the therapeutic potential of modulating CYP-derived EETs and 20-HETE in metabolic diseases are warranted.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Apolipoproteins E; Cytochrome P-450 CYP2J2; Cytochrome P-450 Enzyme System; Diet, High-Fat; Eicosanoids; Enalapril; Gene Expression Regulation, Enzymologic; Hypercholesterolemia; Insulin Resistance; Kidney; Liver; Male; Metabolic Syndrome; Mice; Mice, Knockout; Random Allocation; Renin-Angiotensin System; RNA, Messenger; Severity of Illness Index

Diabetic nephropathy (DN) is a major cause of end-stage renal disease. Yet the pathogenic mechanisms underlying the development of DN are not fully defined, partially due to lack of suitable models that mimic the complex pathogenesis of renal disease in diabetic patients. In this study, we describe early and late renal manifestations of DN and renal responses to long-term treatments with rosiglitazone or high-dose enalapril in ZSF1 rats, a model of metabolic syndrome, diabetes, and chronic renal disease. At 8 weeks of age, obese ZSF1 rats developed metabolic syndrome and diabetes (hyperglycemia, glucosuria, hyperlipidemia, and hypertension) and early signs of renal disease (proteinuria, glomerular collagen IV deposition, tubulointerstitial inflammation, and renal hypertrophy). By 32 weeks of age, animals developed renal histopathology consistent with DN, including mesangial expansion, glomerulosclerosis, tubulointerstitial inflammation and fibrosis, tubular dilation and atrophy, and arteriolar thickening. Rosiglitazone markedly increased body weight but reduced food intake, improved glucose control, and attenuated hyperlipidemia and liver and kidney injury. In contrast, rosiglitazone markedly increased cardiac hypertrophy via a blood pressure-independent mechanism. High-dose enalapril did not improve glucose homeostasis, but normalized blood pressure, and nearly prevented diabetic renal injury. The ZSF1 model thus detects the clinical observations seen with rosiglitazone and enalapril in terms of primary and secondary endpoints of cardiac and renal effects. This and previous reports indicate that the obese ZSF1 rat meets currently accepted criteria for progressive experimental diabetic renal disease in rodents, suggesting that this may be the best available rat model for simulation of human DN.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Glucose; Blood Pressure; Body Weight; Diabetic Nephropathies; Disease Models, Animal; Enalapril; Humans; Hypoglycemic Agents; Kidney; Liver; Male; Metabolic Syndrome; Myocardium; Obesity; PPAR gamma; Rats; Rosiglitazone; Thiazolidinediones

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Drug Therapy, Combination; Enalapril; Heart Rate; Hemodynamics; Humans; Metabolic Syndrome; Models, Biological; Peptidyl-Dipeptidase A; Pyrazines; Sitagliptin Phosphate; Triazoles

Our previous studies have shown vascular dysfunction in small coronary and mesenteric arteries in Zucker obese rats, a model of the metabolic syndrome, and Zucker Diabetic Fatty (ZDF) rats, a model of type 2 diabetes. Because of their lipid lowering action and antioxidant activity, we predicted that treatment with Rosuvastatin, an HMG-CoA reductase inhibitor (statin) or Enalapril, an angiotensin converting enzyme (ACE) inhibitor would improve vascular dysfunction associated with the metabolic syndrome and type 2 diabetes.. 20-week-old Zucker obese and 16-week-old ZDF rats were treated with Rosuvastatin (25 mg/kg/day) or Enalapril (20 mg/kg/day) for 12 weeks. We examined metabolic parameters, indices of oxidative stress and vascular dysfunction in ventricular and mesenteric small arteries (75-175 microm intraluminal diameter) from lean, Zucker obese and ZDF rats (untreated and treated).. Endothelial dependent responses were attenuated in coronary vessels from Zucker obese and ZDF rats compared to responses from lean rats. Both drugs improved metabolic parameters, oxidative stress, and vascular dysfunction in Zucker obese rats, however, only partial improvement was observed in ZDF rats, suggesting more aggressive treatment is needed when hyperglycemia is involved.. Vascular dysfunction is improved when Zucker obese and, to a lesser degree, when ZDF rats were treated with Rosuvastatin or Enalapril.

Topics: Age Factors; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Glucose; Blood Pressure; Body Weight; Cardiovascular Diseases; Cholesterol; Coronary Vessels; Diabetes Mellitus, Type 2; Enalapril; Endothelium, Vascular; Fatty Acids; Fluorobenzenes; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Mesenteric Arteries; Metabolic Syndrome; Oxidative Stress; Pyrimidines; Rats; Rats, Zucker; Rosuvastatin Calcium; Sulfonamides; Triglycerides

Obese Zucker rats, animal model for the metabolic syndrome, develop a diabetes-like neuropathy that is independent of hyperglycemia. The purpose of this study was to determine whether drugs used to treat cardiovascular dysfunction in metabolic syndrome also protect nerve function.. Obese Zucker rats at 20 weeks of age were treated for 12 weeks with enalapril or rosuvastatin. Lean rats were used as controls. Vasodilation in epineurial arterioles was measured by videomicroscopy. Endoneurial blood flow (EBF) was measured by hydrogen clearance and nerve conduction velocity was measured following electrical stimulation of motor or sensory nerves.. Enalapril treatment decreased serum angiotensin-converting enzyme (ACE) activity and both drugs reduced serum cholesterol levels. In obese Zucker rats at 32 weeks of age superoxide levels were elevated in the aortas and epineurial arterioles, which were reduced by treatment with either drug. Nitrotyrosine levels were increased in epineurial arterioles and reduced with enalapril treatment. EBF was decreased and corrected by treatment with either drug. Motor nerve conduction velocity was decreased and significantly improved with enalapril treatment. Obese Zucker rats were hypoalgesic in response to a thermal stimulus and this was significantly improved with either treatment. Treatment with either enalapril or rosuvastatin significantly reversed the decrease in acetylcholine-mediated vascular relaxation of epineurial arterioles in obese Zucker rats.. Even though obese Zucker rats have normal glycemia vascular and neural dysfunctions develop with age and can be improved by treatment with either enalapril or rosuvastatin.

Topics: Acetylcholine; Angiotensin-Converting Enzyme Inhibitors; Animals; Arterioles; Cardiovascular System; Disease Models, Animal; Enalapril; Fluorobenzenes; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Metabolic Syndrome; Motor Neurons; Neural Conduction; Neurons, Afferent; Nociceptors; Obesity; Peripheral Nerves; Pyrimidines; Rats; Rats, Zucker; Rosuvastatin Calcium; Sciatic Nerve; Sulfonamides; Superoxides; Tyrosine; Vasodilator Agents

Moexipril (7.4-15 mg/day) was given to 34, spirapril (3-6 mg/day) -- to 18 postmenopausal women with hypertension and metabolic syndrome for 16 weeks. Hydrochlorthiazide was added when therapy was not sufficiently effective. Both angiotensin converting enzyme inhibitors had similar hypotensive activity: blood pressure normalized in 71 and 61% of moexipril and spirapril treated women, respectively. Both drugs promoted normalization of metabolism of lipid (lowering of levels of cholesterol, atherogenic lipoproteins and triglycerides) and carbohydrates (lowering of hyperinsulinemia). Patients with postmenopausal metabolic syndrome had elevation of leptin level up to 27.5+/-5.5 pg/ml. Moexipril and spirapril caused lowering of elevated levels of leptin. These drugs did not affect levels of sex hormones. They exerted vasoprotective (normalization of endothelium dependent and independent vasodilatation) and nephroprotective (attenuation and normalization of microalbuminuria) effects. Thus spirapril and moexipril are effective in treatment of hypertension in patients with postmenopausal metabolic syndrome.

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Drug Therapy, Combination; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Lipids; Metabolic Syndrome; Middle Aged; Postmenopause; Tetrahydroisoquinolines; Treatment Outcome

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diuretics; Drug Therapy, Combination; Enalapril; Glomerular Filtration Rate; Humans; Hypertension; Male; Metabolic Syndrome; Ramipril; Tetrazoles; Valine; Valsartan

Topics: Blood Platelets; Blood Pressure; Enalapril; Humans; Hypertension; Metabolic Syndrome

Evidence links the insulin resistance syndrome with endothelial dysfunction. Previously, we have described a decreased endothelial nitric oxide synthase (eNOS) activity in both aortic endothelium and cardiac tissue, and an increased proliferation of aortic primary cultured vascular smooth muscle cells (pC-VSMCs), obtained from fructose-fed rats (FFR), an experimental model of syndrome X. Because the participation of the renin-angiotensin system (RAS) in this model is still unclear, the present study examined the effect of chronic administration of an angiotensin converting enzyme (ACE) inhibitor enalapril (E) on pC-VSMCs proliferation and eNOS activity in a conduit artery (aorta) and in resistance vessels (mesenteric vascular bed) from fructose-fed rats. Male Wistar rats were used: Control, FFR, Control + E, and FFR + E (n = 8 in each group). After 8 weeks, tissue samples were obtained and 10% fetal calf serum (FCS) proliferative effect was examined in pC-SMCs of aortic and mesenteric arteries by [(3)H]thymidine incorporation. The eNOS activity was estimated in endothelial lining from both origins by conversion of [(3)H]arginine into [(3)H]citrulline. The FFR aortic and mesenteric pC-VSMCs showed a significantly increased 10% FCS-induced [(3)H]thymidine incorporation compared to controls. The FFR aortic and mesenteric endothelium eNOS activity was significantly decreased. Chronic treatment with E abolished the increased proliferation and restored eNOS activity. These data confirm that changes in VSMCs proliferation and endothelial dysfunction at different levels of the vascular system are involved in syndrome X, and that the inhibition of angiotensin II production can revert those changes, suggesting an important role for RAS and possibly kinins, in the physiopathologic mechanism of this model of syndrome X.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta; Blood Pressure; Cells, Cultured; Coronary Vessels; Disease Models, Animal; Enalapril; Fructose; Male; Mesenteric Arteries; Metabolic Syndrome; Muscle, Smooth, Vascular; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Rats; Rats, Wistar