enalapril and Hyperglycemia

Diabetic nephropathy (DN) is a leading cause of kidney disease in the US. At least four factors influence whether people with diabetes will develop DN: (1) hypertension, (2) hyperglycemia, (3) dietary protein intake, and (4) intrarenal hemodynamics. The angiotensin-converting enzyme (ACE) inhibitors are known to affect blood pressure (BP) and intrarenal hemodynamics; thus, they may prevent the onset of DN or slow the decline in renal function once DN has been diagnosed.. English-language, controlled, and crossover studies published between 1973 and 1991 and indexed in MEDLINE under the headings diabetic nephropathies and angiotensin-converting enzyme inhibitors.. The primary outcome indicators of interest were the effects of the ACE inhibitors captopril, enalapril, and lisinopril on BP control and urinary albumin excretion rate.. ACE inhibitors delay the onset and slow the progression of DN in people with diabetes independent of BP effects. They also slow the progression of DN in people with diabetes who have poorly controlled hyperglycemia. The proper dose and time at which to initiate ACE inhibitor therapy to prevent the appearance of DN is not known. It is also not known how long the beneficial effects of ACE-inhibitor therapy persists as only two studies have followed patients for more than one year. Finally, large, long-term, controlled clinical trials are needed before ACE inhibitors can be considered for prophylactic use to prevent the onset and/or progression of DN.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Capillary Resistance; Captopril; Diabetic Nephropathies; Dipeptides; Enalapril; Humans; Hyperglycemia; Lisinopril

Diabetes mellitus reduces female gender-mediated protection against progression of renal disease but the mechanisms responsible for this loss of protection are unknown. The impact of gender on the diabetic hyperfiltration state has not previously been studied. Since hyperfiltration is a factor in the development of diabetic renal disease, and is influenced by hyperglycemia and renin-angiotensin system (RAS) blockade, we examined gender differences in the renal response to hyperglycemia and angiotensin-converting enzyme (ACE) inhibition in young males and females with uncomplicated type 1 diabetes mellitus.. Ten male and 12 female normoalbuminuric, normotensive, adolescents with type 1 diabetes mellitus were studied before ACE inhibition during clamped euglycemia and hyperglycemia, and then after 21 days treatment with enalapril (0.1 mg/kg daily x 1 week and then 0.1 mg/kg twice a day x 2 weeks).. During clamped euglycemia, males exhibited significantly higher effective renal plasma flow (ERPF) and renal blood flow (RBF) and a lower renal vascular resistance (RVR). During clamped hyperglycemia, females exhibited reductions in ERPF and RBF, and increased RVR and filtration fraction (FF). Males exhibited no significant renal hemodynamic changes during hyperglycemia. After ACE inhibition treatment, both genders exhibited significant declines in arterial pressure, but only females displayed a reduction in glomerular filtration rate (GFR) and FF.. The renal responses to hyperglycemia and ACE inhibition appear to differ between male and female adolescents with uncomplicated type 1 diabetes mellitus. Hyperglycemia-induced changes in RVR and FF in women may account, at least in part, for the loss of gender-based protection in diabetic renal disease.

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Cohort Studies; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Enalapril; Female; Glomerular Filtration Rate; Glucose Clamp Technique; Humans; Hyperglycemia; Hypertension, Renal; Kidney; Renal Circulation; Sex Characteristics; Treatment Outcome

To investigate whether endogenous bradykinin is involved in the antioxidant action of angiotensin-converting enzyme inhibitors (ACEIs) in acute hyperglycemia.. Male Wistar rats were divided into the normoglycemic group (n=40) and the hyperglycemic group (n=40). Hyperglycemia was induced by a single intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) dissolved in 0.1 mol/L citrate buffer (pH 4.5) 72 hours before sacrifice. The normoglycemic group received the same volume of citrate buffer. Each group was divided into five subgroups (n=8): control group, captopril group, captopril + bradykinin B1 and B2 receptor antagonists group, enalapril group, and enalapril + bradykinin B1 and B2 receptor antagonists group. Captopril, enalapril, B1 and B2 receptor antagonists, or 0.15 mol/L NaCl were given at 2 and 1 hour before sacrifice. Oxidative status was determined by measuring the concentration of malondialdehyde and H2O2, and the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx).. In STZ-induced hyperglycemic rats ACEIs significantly reduced H2O2 concentration, while they significantly enhanced SOD and GPx activity. The hyperglycemic group treated simultaneously with ACEIs and bradykinin B1 and B2 receptor antagonists showed a significant decrease in H2O2 concentration compared to the control hyperglycemic group.. These results suggest the existence of the bradykinin -independent antioxidative effect of ACEIs in hyperglycemic conditions, which is not related to the bradykinin mediation and the structure of the drug molecule.

Topics: Adrenergic beta-Agonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin Receptor Antagonists; Captopril; Catalase; Enalapril; Glutathione Peroxidase; Hydrogen Peroxide; Hyperglycemia; Male; Malondialdehyde; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase

To evaluate the frequency of normalization, the persistence of remission, and the impact on normalization of glycemic control and lipid profile, we analyzed data from a retrospective observational cohort study of type 1 diabetic children and adolescents with abnormal urinary albumin excretion (UAE).. All diabetic children and adolescents (n = 41) who had persistent abnormal UAE in the period of 1984 to 2008 and followed up until 2009 (follow-up duration = 13.1 ± 6.2 years) were included in the study. Nine patients progressed to macroalbuminuria; 24 patients were administered ACE inhibitor treatment.. The cumulative prevalence of abnormal UAE was 9%. During follow-up, 14 of 17 untreated and 19 of 24 treated patients reverted to normoalbuminuria. In the remission group compared with the nonremission group, A1C levels during follow-up decreased (7.5 ± 1.0 vs. 9.4 ± 1.2%, P < 0.0001) and serum HDL cholesterol increased (52.7 ± 11.3 vs. 42.7 ± 8.6 mg/dL, P < 0.05). The micro-macroalbuminuric patients had lower HDL cholesterol (51.0 ± 11.4 vs. 62.4 ± 13.6 mg/dL, P < 0.0001) than 134 normoalbuminuric diabetic patients.. Microalbuminuria and macroalbuminuria were not permanent in most of our diabetic children and adolescents. If abnormal UAE values are high and persist for >1 year, only long-lasting treatment with ACE inhibitors seems able to induce persistent remission, especially when associated with good metabolic control and high HDL cholesterol levels.

Topics: Adolescent; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Child; Cholesterol, HDL; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Disease Progression; Enalapril; Follow-Up Studies; Humans; Hyperglycemia; Longitudinal Studies; Prevalence; Remission Induction; Retrospective Studies

Many adrenergic agonists including isoproterenol, a beta1,2-adrenergic agonist, reduce alcohol consumption, but the mechanism of this effect is not known. Adrenergic agonists have a variety of effects, among which are their ability to raise both angiotensin (ANG) II activity and plasma glucose levels. Previous research has shown that ANG II and enhanced glucose levels are accompanied by reductions in alcohol intake. Therefore, the following experiments assessed the roles of each of these factors in the suppression of alcohol intake by isoproterenol. Male Wistar rats were trained to drink a quantity of 6% (w/v) alcohol using the limited access procedure, which offers a daily 40-min access to alcohol and water. In experiment 1, isoproterenol or vehicle was administered s.c. just prior to alcohol availability, and only the group receiving isoproterenol showed a marked reduction in alcohol intake. Following this, the groups were pretreated i.p. with either vehicle or ascending doses of the prostaglandin synthetase inhibitor, indomethacin (2, 4 mg/kg), followed by either isoproterenol or vehicle. Control groups received either two vehicle injections or vehicle and indomethacin. Indomethacin alone did not affect alcohol intake at any of the doses tested but did dose-dependently attenuate the reduction in alcohol intake produced by isoproterenol. In experiment 2, isoproterenol was administered just prior to alcohol availability and when the suppression of alcohol intake stabilized, ascending doses of the angiotensin converting enzyme inhibitor, enalapril (1, 20, 40 mg/kg), were given i.p. 1 h prior to the isoproterenol. Enalapril altered water intake but had no effect on the isoproterenol-induced reduction in alcohol intake. These results show that the inhibition of alcohol drinking by isoproterenol varies more closely with altered glucose levels than with increased ANG II synthesis. They also demonstrate that downstream consequences of a drug may play a role in its effect on alcohol intake.

Topics: Adrenergic beta-Agonists; Alcohol Drinking; Analysis of Variance; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Glucose; Drinking; Enalapril; Ethanol; Hyperglycemia; Indomethacin; Isoproterenol; Male; Rats; Rats, Wistar

Glomerular ultrafiltration coefficient, Kf, is diminished in established diabetic nephropathy. To determine whether Kf is decreased because of a decrease in capillary area, A, and or in hydraulic conductivity, Lp, glomerular Kf and morphometric parameters were measured, and Lp was calculated in glomeruli of young rats with STZ-induced DM and in control rats. STZ was administered to Fischer 344 rats that weighted 50-75 g; glomeruli were examined after 3 or 5 mo of DM, and their structure and function was compared with that of control rats. The effects of insulin or of an ACEI, enalapril, also were assessed after 3 or 5 mo. Growth of DM rats was markedly impaired, and their ratio of kidney weight to body weight was increased. Ccr was proportional to rat weight, and the ratio of Ccr to body weight was not different in DM and control rats. At 3 mo, average volume of glomeruli isolated from DM rats was less than that of glomeruli from control rats. In contrast, glomerular volume after 5 mo was equal in DM and control rats. No increase in GBM thickness or mesangial volume was observed, nor was any decrease seen in GBM area in DM rats at 5 mo. Kf was lower in DM rats than controls after 3 mo, but not after 5 mo. The Lp of DM and control glomeruli did not differ at 3 mo, but was lower in DM at 5 mo. Insulin therapy improved somatic growth and increased kidney and glomerular size in DM rats; the kidney weight/body weight ratio remained elevated.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Basement Membrane; Capillary Permeability; Cell Membrane Permeability; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Enalapril; Glomerular Filtration Rate; Glomerular Mesangium; Hemodynamics; Hyperglycemia; Insulin; Kidney; Male; Organ Culture Techniques; Organ Size; Rats; Rats, Inbred F344