enalapril and Weight-Gain

The safety of testosterone supplements in men remains unclear. In the present study, we tested the hypothesis that in young and old male spontaneously hypertensive rats (SHR), long-term testosterone supplements increase blood pressure and that the mechanism is mediated in part by activation of the renin-angiotensin system.. In untreated males, serum testosterone exhibited a sustained decrease after 5 months of age, reaching a nadir by 18 to 22 months of age. The reductions in serum testosterone were accompanied by an increase in body weight until very old age (18 months). Testosterone supplements were given for 6 weeks to young (12 weeks-YMSHR) and old (21-22 months-OMSHR) male SHR that increased serum testosterone by 2-fold in young males and by 4-fold in old males. Testosterone supplements decreased body weight, fat mass, lean mass, and plasma leptin, and increased plasma estradiol in YMSHR but had no effect in OMSHR. Mean arterial pressure (MAP) was significantly higher in OMSHR than in YMSHR and testosterone supplements decreased MAP in OMSHR, but significantly increased MAP in YMSHR. Enalapril, the angiotensin-converting enzyme inhibitor, reduced MAP in both control and testosterone-supplemented YMSHR, but had a greater effect on MAP in testosterone-treated rats, suggesting the mechanism responsible for the increase in MAP in YMSHR is mediated at least in part by activation of the renin-angiotensin system.. Taken together with previous studies, these data suggest that testosterone supplements may have differential effects on men depending on age, cardiovascular and metabolic status, and dose and whether given long-term or short-term.

Topics: Adiposity; Age Factors; Aging; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Arterial Pressure; Disease Models, Animal; Enalapril; Estradiol; Hormone Replacement Therapy; Hypertension; Leptin; Male; Rats, Inbred SHR; Renin-Angiotensin System; Risk Factors; Testosterone; Weight Gain

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Enalapril; Longevity; Male; Weight Gain

Neuroglucopenia induced by 2-deoxy-D-glucose (2DG) activates hypothalamic glucoreceptors leading to increased hepatic glucose production and insulin inhibition. This response is similar to what is observed with intravenous injection of angiotensin II (Ang II). However, the involvement of an angiotensin-converting enzyme inhibitor on neuroglucopenia has not been investigated. The aim of this study was to determine the effects of chronic enalapril treatment on plasma glucose, insulin and lipid levels in response to neuroglucopenia. Male Holtzman rats (120-170 g) were chronically treated with enalapril (10 mg/kg per day) in the drinking water for two weeks. On the day of experiment the animals received an i.v. enalapril final dose one hour before the neuroglucopenic stress by 2DG infusion (500 mg/kg), and blood samples were drawn before and 5, 10, 20, 30 and 60 minutes following infusion. The hyperglycaemic response to 2DG was not significantly changed by enalapril treatment. The enalapril-treated group exhibited a peak of plasma insulin higher than controls. Plasma triglyceride showed a significant increase only in the enalapril group after neuroglucopenic stress (p < 0.05).These data show that chronic enalapril treatment changes insulin and triglyceride responses to neuroglucopenia, suggesting an effect on glucose-induced insulin secretion and the storage of triglycerides.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Glucose; Body Weight; Cholesterol; Deoxyglucose; Drinking Behavior; Enalapril; Glucose; Insulin; Male; Neurons; Peptidyl-Dipeptidase A; Rats; Stress, Physiological; Time Factors; Triglycerides; Weight Gain

Renin-angiotensin system is involved in homeostasis processes linked to renal and cardiovascular system and recently has been linked to metabolic syndrome. We analyzed the influence of long term angiotensin I converting enzyme (ACE) inhibitor enalapril treatment in normotensive adult Wistar rats fed with standard or palatable hyperlipidic diets. Our results show that long term enalapril treatment decreases absolute food intake, serum leptin concentration and body weight gain. Moreover, in adipose tissue, enalapril treatment led to decreased ACE activity, enhanced the expression of peroxisome proliferator activated receptor gamma, adiponectin, hormone-sensitive lipase, fatty acid synthase, catalase and superoxide dismutase resulting in prolonged life span. On the other hand, the ACE inhibitor was not able to improve the transport of leptin through the blood brain barrier or to alter the sensitivity of this hormone in the central nervous system. The effect of enalapril in decreasing body weight gain was also observed in older rats. In summary, these results extend our previous findings and corroborate data from the literature regarding the beneficial metabolic effects of enalapril and show for the first time that this ACE inhibitor prolongs life span in rats also fed with palatable hyperlipidic diet, an action probably correlated with adipose tissue metabolic modulation and body weight reduction.

Topics: Adiponectin; Adipose Tissue; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Catalase; Eating; Enalapril; Energy Intake; Fatty Acid Synthases; Insulin; Leptin; Longevity; Male; PPAR gamma; Random Allocation; Rats; Rats, Wistar; Sterol Esterase; Superoxide Dismutase; Time Factors; Weight Gain

Recently, we have shown that chronic administration of N-Nitro-L-Arginine Methyl Ester (L-NAME, an inhibitor of nitric oxide synthase) precipitates stroke in stroke-prone spontaneously hypertensive rats (SHRSP). Enalapril maleate, an angiotensin converting enzyme inhibitor was shown to delay the onset of such stroke. In the present study, five groups of 4-week-old SHRSP were used. Three groups of SHRSP were made diabetic using streptozotocin (100 mg/kg i.p.). One week later, the SHRSP from groups I (non-diabetic) and III (diabetic) chronically received L-NAME (0.5 g/L) in saline as drinking water. Two SHRSP groups, II (non-diabetic) and IV (diabetic) received L-NAME (0.5 g/L) and enalapril maleate (20 mg/L) in saline as drinking water. Control SHRSP (group C; diabetic) received only saline to drink. SHRSP groups I and III developed stroke in 10+/-2 and 11+/-2 days, respectively. The average stroke-free period in groups II and IV was 19+/-2 and 28+/-2 days, respectively. Protective effect of streptozotocin-induced diabetes disappeared when SHRSP drinking L-NAME and enalapril, concurrently received subcutaneous injections of insulin (2 units daily per 100 g rat). Present data suggest that experimental diabetes delays the onset of L-NAME-induced stroke in SHRSP only in the absence of angiotensin converting enzyme activity. In addition, diabetes-induced enhancement of stroke-protective effect of enalapril appears to be independent of reduction in mean and systolic blood pressures.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cerebrovascular Disorders; Diabetes Mellitus, Experimental; Enalapril; Endothelin-1; Hypertension; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Rats; Rats, Inbred SHR; Streptozocin; Weight Gain

Angiotensin-converting enzyme inhibitors (ACEIs) have been suggested to reduce interdialytic fluid weight gain, presumably via suppression of the dipsogenic angiotensin II. We retrospectively studied 25 (76% black) chronic hemodialysis patients who received ACEIs for blood pressure control. The mean arterial blood pressure decreased from 115.4 +/- 10.4 mm Hg to 112.7 +/- 9.0 mm Hg (mean +/- SD; P = NS) and there was no change in the interdialytic weight gain (3.74 +/- 1.5 kg v 3.72 +/- 1.5 kg; P = NS). Only 10 (40%) patients had some reduction in their interdialytic weight gain; in four of them the reduction was more than 20% of the pre-ACEI weight gain. When nine patients who had no decline in blood pressure were excluded due to possible noncompliance, the mean arterial blood pressure in the remaining 16 patients (75% black) declined from 119.3 +/- 9.9 mm Hg to 111.6 +/- 9.9 mm Hg (P < 0.0001), but there was no change in the interdialytic fluid weight gain (3.7 +/- 1.4 kg v 3.8 +/- 1.4 kg; P = NS). There was no correlation between age, race, etiology of renal failure, or blood pressure response and change in the interdialytic weight gain after ACEI treatment. Our results do not support the previous report that ACEIs significantly decrease the interdialytic weight gain in chronic hemodialysis patients. The multifactorial nature of excessive fluid intake in the hemodialysis patients and the differences in patient population and study design may account for this discrepancy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Black People; Captopril; Enalapril; Fosinopril; Humans; Hypertension; Kidney Failure, Chronic; Middle Aged; Renal Dialysis; Retrospective Studies; Weight Gain