glycogen and Hypertension

Topics: Carbohydrate Metabolism; Glucose; Glycogen; Humans; Hypertension; Neutrophils; Oxidation-Reduction; Renal Dialysis; Uremia

The use of beta-blockers in diabetes mellitus has largely been restricted because of the reported adverse effects. Clinical investigations aimed at elucidating the possible reactions associated with the use of beta-blockers have disclosed no evidence of masking or signs or insulin-induced hypoglycaemia or potentiation of the insulin effect. Prolonged hypoglycaemia may develop, however, as a result of physical effort. There is no proof that during insulin-induced hypoglycaemia the concentrations of counter-regulatory hormones are depressed, but that of glycerol, a gluconeogenic precursor, is slightly diminished. Intensification of the hypertensive reaction during hypoglycaemia is less likely to occur during treatment with beta-selective blockers. In insulin-dependent diabetics receiving beta 1-blockers there is no evidence of any change - either deterioration or improvement - in metabolic control. In one small controlled trial there was no sign of impairment of the peripheral arterial circulation over a short period of administration of a non-selective beta-blocker. In general, for patients suffering from insulin-dependent diabetes, cardioselective agents are preferable. Since cardioselectivity is a dose-dependent property, reasonable caution should also be observed when using this type of drug in diabetes.

Topics: Adrenergic beta-Antagonists; Alprenolol; Blood Glucose; Catecholamines; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Drug Synergism; Fatty Acids, Nonesterified; Gluconeogenesis; Glucose Tolerance Test; Glycerol; Glycogen; Humans; Hypertension; Hypoglycemia; Insulin; Lactates; Lactic Acid; Metoprolol; Oxprenolol; Propranolol

Topics: Adrenal Cortex Hormones; Animals; Anti-Inflammatory Agents; Arteries; Arteriosclerosis; Cats; Cattle; Cholesterol; Diabetes Complications; DNA; Epinephrine; Glycogen; Glycolysis; Humans; Hypertension; Hypoxia; Isoenzymes; L-Lactate Dehydrogenase; Lipid Metabolism; Oxidoreductases; Pentoses; Phosphofructokinase-1; Phospholipids; Phosphorylases; Rabbits; Rats; Swine; Thrombosis

Geriatric cardiology requires special knowledge and experience. It is not possible to extrapolate directly experience obtained with young patients to old people. Because of the multiple illnesses, many serious, in the elderly cardiac patients, it is imperative for the cardiologist to be, first of all, a master internist at all times. Old patients with their multiple illnesses are also sensitive to drugs, including digitalis and diuretics. There is a need to train more physicians in geriatric cardiology in order to offer the old patient the best of care since so many old people are living today. There is also a need to learn the effects of the aging process itself on the human heart. Such studies should command priorities in financial and other forms of support.

Topics: Age Factors; Aging; Aortic Valve Insufficiency; Aortic Valve Stenosis; Cardiac Output; Dyspnea; Edema; Electrocardiography; Female; Glycogen; Heart; Heart Diseases; Heart Function Tests; Histocytochemistry; Humans; Hypertension; Hypotension, Orthostatic; Male; Microscopy, Electron; Myocardium; Radiography; Rheumatic Heart Disease; Thyroid Diseases; Vectorcardiography

Topics: Acid-Base Equilibrium; Adrenergic beta-Agonists; Blood Glucose; Carbohydrate Metabolism; Cardiovascular System; Catechol O-Methyltransferase; Catecholamines; Cyclic AMP; Energy Metabolism; Fats; Female; Fetal Heart; Fetus; Glycogen; Humans; Hypertension; Hypotension; Infant, Newborn; Insulin; Maternal-Fetal Exchange; Placenta; Potassium; Pregnancy; Respiration; Time Factors; Uterine Contraction

The information that insulin sensitivity and glycogen synthesis are reduced in hypertension arises primarily from studies using insulin infusions. Whether glycogen metabolism is actually altered in a physiological condition, such as during and after prolonged exercise, is currently unknown.. To examine this issue, 9 hypertensive and 11 normotensive subjects were evaluated on a rest day and after intense and prolonged exercise on a separate day. Insulin sensitivity and hemodynamic variables were measured on both days. On the exercise day, whole-body substrate utilization was assessed and muscle biopsies were taken in the leg at baseline, immediately after exercise, and 2.5 and 4 hours after exercise. Insulin sensitivity at rest was lower in hypertensive than normotensive subjects (P<0.05) and increased after exercise in normotensive (P<0.01) but not in hypertensive (P=NS) subjects. Leg blood flow increased after exercise in both groups but to a lesser extent in hypertensive than normotensive subjects. Baseline glycogen content and maximal glycogen synthase activity were higher in hypertensive than normotensive subjects (P<0.001). Glycogen concentration decreased relatively less (-35 versus -66%) and returned to baseline levels faster in hypertensive subjects after exercise. Hypertensive subjects used approximately 40% less carbohydrates during exercise (P<0.001) at the expense of greater free fatty acid oxidation.. It is concluded that increased intramuscular glycogen storage and resynthesis in hypertension are independent of blood flow and may represent compensatory mechanisms for the reduced insulin sensitivity and carbohydrate metabolism in this condition.

Topics: Adult; Biopsy; Blood Pressure; Glucose Tolerance Test; Glycogen; Glycogen Synthase; Hemodynamics; Humans; Hypertension; Insulin Resistance; Leg; Male; Muscle, Skeletal; Oxygen Consumption; Physical Exertion; Reference Values; Regional Blood Flow

The hemodynamic and metabolic consequences of long-term antihypertensive treatment with beta 1- and beta 1/beta 2-adrenoceptor blockade was investigated in five young men with mild essential arterial hypertension (World Health Organization stages I and II) at rest and during submaximal exercise in a single-blind crossover study. The drugs (atenolol and alprenolol) were given in equipotent doses as estimated from their effects on blood pressure. Leg blood flow and oxygen uptake were the same during both treatment periods. Muscle glycogen decreased by 40% during exercise, irrespective of the drug. There was a positive relationship between muscle lactate release and concentration, but for a given muscle lactate concentration the release tended to be lower during treatment with alprenolol. A negative correlation was observed between the percentage of slow-twitch fibers versus lactate release and muscle lactate concentration. The results demonstrate that during exercise muscle glycogen breaks down despite beta blockade and is neither reduced when both beta 1- and beta 2-receptors are blocked, nor when only the beta 1-receptors are blocked. It is also shown that beta blockade impairs the translocation of lactate from the muscle cell to the blood and this is greater with alprenolol than with atenolol, probably due to a membrane effect.

Topics: Adrenergic beta-Antagonists; Glycogen; Hemodynamics; Humans; Hypertension; Lactates; Male; Muscles; Oxygen Consumption

The effects of microcapsules containing brewer's spent grain (BSG) peptides were evaluated on a hypertensive/insulin-resistant rat model induced by a sucrose-rich diet (SRD) administration. Animals received for 100 days the control diet (CD), SRD, and CD and SRD diets supplemented with microencapsulated peptides (CD-P and SRD-P). During the experimental period, blood pressure was monitored. Glycemia, tissue glycogen content, nitric oxide, and the activity of enzymes related to hypertensive and diabetogenic mechanisms were determined. The consumption of SRD caused hypertensive and hyperglycemic effects compared to CD. However, the SRD-P group presented lower systolic pressure at the middle of ingestion, achieving similar values than the CD. The SRD-P rats decreased all enzymes' activities compared to the SRD reaching the values of CD, except for those of α-amylase in cecal content and DPP-IV in serum. It was possible to corroborate potential antihypertensive and antidiabetogenic in vivo effects of the microencapsulated BSG peptides. PRACTICAL APPLICATIONS: Brewer's spent grain (BSG) is the main waste obtained from brewing industry. Bioactive peptides obtained after an enzymatic hydrolysis of proteins with in vitro antihypertensive and antidiabetogenic activity have been described. However, to corroborate the action of these bioactive peptides, in vivo studies are necessary. In the present work, microcapsules containing bioactive peptides from BSG were administered on the rat model with induced hypertension and insulin-resistance, corroborating an in vivo antihypertensive and antidiabetogenic effects by inhibition of enzymes related with blood pressure regulation and glucose metabolism. This work demonstrated that microcapsules of BSG peptides could be included into functional foods formulations, or used as dietary supplement for improving health and the prevention of non-communicable diseases, adding value to the brewing process by-product.

Topics: alpha-Amylases; Animals; Antihypertensive Agents; Capsules; Edible Grain; Glucose; Glycogen; Hypertension; Insulin; Nitric Oxide; Peptides; Rats; Sucrose

Recent interest in the use of cannabinoids as therapeutic agents has revealed the involvement of the endogenous cannabinoid system (ECS) in the regulation of the cardiovascular system in hypertension. Abnormalities in glucose metabolism and insulin action are commonly detected in hypertensive animals. Thus, potential antihypertensive drugs should be investigated with respect to modulation of glucose homeostasis. Therefore, the aim of the present study was to evaluate the effects of the ECS activation after chronic fatty acid amide hydrolase inhibitor (URB597) administration on plasma glucose and insulin concentrations as well as parameters of myocardial glucose metabolism in the deoxycorticosterone acetate (DOCA)-salt hypertensive rats, an animal model of secondary hypertension.. Hypertension was induced by DOCA (25mg/kg) injections and addition of 1% NaCl in the drinking water for six weeks. Chronic activation of the ECS was performed by URB597 (1mg/kg) injections for two weeks. We examined fasting plasma levels of insulin (ELISA), glucose and intramyocardial glycogen (colorimetric method). Expressions of glucose transporters (GLUT1, 4) and selected proteins engaged in GLUT translocation as well as glucose metabolism were determined using Western blotting.. Hypertension induced hypoinsulinemia with concomitant lack of significant changes in glycemia, reduced intramyocardial glycogen content and increased pyruvate dehydrogenase (PDH) expression in the cardiac muscle. Importantly, chronic URB597 administration in the hypertensive rats increased insulin concentration, elevated plasmalemmal GLUT1 and GLUT4 expression and concomitantly improved myocardial glycogen storage.. Chronic administration of fatty acid amide hydrolase (FAAH) inhibitor has potential protective properties on myocardial glucose metabolism in hypertension.

Topics: Animals; Benzamides; Blood Glucose; Carbamates; Desoxycorticosterone Acetate; Glucose; Glucose Transporter Type 1; Glucose Transporter Type 4; Glycogen; Hypertension; Insulin; Ketone Oxidoreductases; Male; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Myocardium; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar

Vascular abnormalities and glycogen accumulation in vascular smooth muscle fibres have been described in Pompe disease. Using carotid-femoral pulse wave velocity (cfPWV), the gold standard methodology for determining aortic stiffness, we studied whether aortic stiffness is increased in patients with Pompe disease. Eighty-four adult Pompe patients and 179 age- and gender-matched volunteers participated in this cross-sectional case-controlled study. Intima media thickness and the distensibility of the right common carotid artery were measured using a Duplex scanner. Aortic augmentation index, central pulse pressure, aortic reflexion time and cfPWV were assessed using the SphygmoCor® system. CfPWV was higher in patients than in volunteers (8.8 versus 7.4 m/s, p < 0.001). This difference was still present after adjustment for age, gender, mean arterial blood pressure (MAP), heart rate and diabetes mellitus (p = 0.001), and was shown by subgroup analysis to apply to the 40-59 years age group (p = 0.004) and 60+ years age group (p = 0.01), but not to younger age groups (p = 0.99). Except for a shorter aortic reflexion time (p = 0.02), indirect indicators of arterial stiffness did not differ between patients and volunteers. Relative to volunteers (20%), more Pompe patients had a history of hypertension (36%, p = 0.005), and the MAP was higher than in volunteers (100 versus 92 mmHg, p < 0.001). This study shows that patients with non-classic Pompe disease have increased aortic stiffness and blood pressure. Whether this is due to glycogen accumulation requires further investigation. To reduce the potential risk of cardiovascular diseases, we recommend that blood pressure and other common cardiovascular risk factors are monitored regularly.

Topics: Adult; Blood Pressure; Case-Control Studies; Cross-Sectional Studies; Enzyme Replacement Therapy; Female; Glycogen; Glycogen Storage Disease Type II; Humans; Hypertension; Male; Middle Aged; Muscle, Smooth, Vascular; Pulse Wave Analysis; Vascular Stiffness

The Spontaneously Hypertensive Heart Failure (SHHF) rat mimics the human progression of hypertension from hypertrophy to heart failure. However, it is unknown whether SHHF animals can exercise at sufficient levels to observe beneficial biochemical adaptations in skeletal muscle. Thirty-seven female SHHF and Wistar-Furth (WF) rats were randomized to sedentary (SHHFsed and WFsed) and exercise groups (SHHFex and WFex). The exercise groups had access to running wheels from 6-22 months of age. Hindlimb muscles were obtained for metabolic measures that included mitochondrial enzyme function and expression, and glycogen utilization. The SHHFex rats ran a greater distance and duration as compared to the WFex rats (P<0.05), but the WFex rats ran at a faster speed (P<0.05). Skeletal muscle citrate synthase and beta-hydroxyacyl-CoA dehydrogenase enzyme activity was not altered in the SHHFex group, but was increased (P<0.05) in the WFex animals. Citrate synthase protein and gene expression were unchanged in SHHFex animals, but were increased in WFex rats (P<0.05). In the WFex animals muscle glycogen was significantly depleted after exercise (P<0.05), but not in the SHHFex group. We conclude that despite robust amounts of aerobic activity, voluntary wheel running exercise was not sufficiently intense to improve the oxidative capacity of skeletal muscle in adult SHHF animals, indicating an inability to compensate for declining heart function by improving peripheral oxidative adaptations in the skeletal muscle.

Topics: 3-Hydroxyacyl CoA Dehydrogenases; Adaptation, Physiological; Animals; ATP Citrate (pro-S)-Lyase; Disease Models, Animal; Energy Metabolism; Female; Glycogen; Glycolysis; Heart Failure; Hindlimb; Hypertension; Muscle Contraction; Muscle, Skeletal; Physical Exertion; Rats; Rats, Inbred SHR; Rats, Inbred WF; RNA, Messenger; Running; Time Factors

Type 2 diabetes is quite diverse, including the improvement of insulin sensitivity by dipeptidylpeptidase-4 (DPP-4) inhibitor, α-glucosidase inhibitors, and the protection of β-cells islet. The aim of this study was to search the effect of trigonelline (Trig) on DPP-4, α-glucosidase and angiotensin converting enzyme (ACE) activities as well as β-cells architecture, and starch and glucose tolerance test. In surviving diabetic rats, the supplement of Trig potentially inhibited DPP-4 and α-glucosidase activities in both plasma and small intestine. The pancreas islet and less β-cells damage were observed after the administration of trig to diabetic rats. The increase of GLP-1 in surviving diabetic rats suppressed the increase of blood glucose level and improved results in the oral glucose and starch tolerance test. Trig also normalized key enzyme related to hypertension as ACE and improved the hemoglobin A1c and lipid profiles (plasma triglyceride, HDL-cholesterol, LDL-cholesterol, and total cholesterol), and liver indices toxicity. Therefore, these results revealed that Trig was successful in improving glycemic control, metabolic parameters, and liver function in diabetic rats. It is therefore suggested that Trig may be a potential agent for the treatment of type 2 diabetes.

Topics: Alkaloids; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Glucose Tolerance Test; Glycated Hemoglobin; Glycogen; Hypertension; Insulin-Secreting Cells; Intestines; Liver; Liver Function Tests; Male; Rats; Rats, Wistar

The goal of this study was to examine the effect of Virgin Argan Oil (VAO) obtained from the fruit of Argania spinosa in a model of type 2 diabetes and hypertensive rats. Neonatal diabetes was induced by a single i.p. injection of streptozotocin (90 mg/kg) 2 days after birth. To induce NO-deficient hypertension, the adult diabetic animals were treated with l-nitroarginine methylester (l-NAME) (30 mg/kg/day) given orally for 21 days.. Following treatment with VAO (21 days), the hyperglycemia decreased to 1.3 ± 0.07 g/l compared with 1.92 ± 0.09 g/l (p < 0.01) in the untreated diabetic-hypertensive rats. The simultaneous administration of VAO with l-NAME prevented the increase in blood pressure during the 3 weeks of treatment. Blood pressure remained constant at 131 ± 1 mm Hg after 21 days - vs 157 ± 0.64 mm Hg in untreated animals (p < 0.001).. The treatment with VAO to diabetic-hypertensive rats caused a significant increase of hepatic glycogen levels (13.3 ± 1.8 vs 6.34 ± 0.75 mg/g tissue in untreated diabetic-hypertensive control group; p < 0.01).. In conclusion, the overall findings indicate that VAO possesses antidiabetic and antihypertensive activity in n-stz/l-NAME rats. This effect may be related to its high content of tocopherols, phenolic compounds, and unsaturated fatty acids.

Topics: Animals; Animals, Newborn; Antihypertensive Agents; Blood Glucose; Blood Pressure; Diabetes Mellitus, Experimental; Glycogen; Hyperglycemia; Hypertension; Hypoglycemic Agents; Liver; NG-Nitroarginine Methyl Ester; Phytotherapy; Plant Oils; Rats; Rats, Wistar; Sapotaceae

Cilnidipine (Cil) is an L/N-type calcium channel blocker (CCB) that is known to provide renal protection by decreasing the activity of the sympathetic nervous system and the renin-angiotensin system (RAS). However, very few studies have evaluated the renoprotective effects of Cil in hypertension complicated by diabetes mellitus. In this study, we compared the effects of cilnidipine and the L-type CCB, amlodipine (Aml), in combination with an angiotensin II receptor blocker (ARB) on diabetic nephropathy that developed as a result of inducing diabetes in hypertensive rats.. Diabetes was induced in 9-week-old male spontaneously hypertensive rats by intraperitoneally injecting them with streptozotocin (40 mg/kg twice) and the rats (8 per group) were randomly assigned to receive valsartan (Val), Cil + Val, Aml + Val, or vehicle for 8 weeks through a gastric tube.. There were no significant differences in systolic blood pressure or plasma parameters between the two combination therapy groups. Blood pressure lowering by neither combination therapy significantly affected the glycemic variables. However, the increased glycogen levels in the kidney as a result of hyperglycemia were significantly suppressed in the groups that received combination therapy, and the increased proteinurea and glomerulosclerosis due to progression of the diabetic nephropathy were significantly suppressed in the Cil + Val group. In addition, a significant decrease in ED-1-positive cells was observed in the Cil + Val group alone.. The results of this study suggested that the L/N-type CCB, cilnidipine, had additive antihypertensive and proteinuria-lowering effects when administered in combination with an ARB, even in type-1 diabetic rats, and that the L-type CCB, amlodipine, did not. Furthermore, combination therapy with cilnidipine and valsartan significantly reduced glycogen accumulation and ED-1-positive cell infiltration, suggesting that cilnidipine suppressed the excessive increase in the activity of the sympathetic nervous system and RAS through N-type calcium channel blockade.

Topics: Amlodipine; Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Biomarkers; Blood Glucose; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Dihydropyridines; Disease Progression; Drug Therapy, Combination; Glomerulonephritis; Glucagon; Glucose Transporter Type 1; Glycated Hemoglobin; Glycogen; Hypertension; Kidney; Male; Norepinephrine; Proteinuria; Rats; Rats, Inbred SHR; Renin-Angiotensin System; Tetrazoles; Transforming Growth Factor beta1; Valine; Valsartan

Transient administration of inhibitors of the renin-angiotensin system (RAS) during the prehypertensive period in rats and humans leads to a long-lasting lowering of blood pressure (BP). Our aim was to unravel the critical period in which activation of the RAS induces chronic effects on BP and to determine the role of renal function and structure in this process.. Studies were performed in Cyp1a1-Ren2 rats, which harbor a construct for the production of mouse renin. This construct becomes activated when indole-3-carbinol (I3C) is added to the diet. Young (4 weeks old) and adult (30 weeks old) Cyp1a1-Ren2 rats were randomly assigned to either the I3C treatment group or the control group. Renin production was stimulated from week 4 to 8 in young and week 30 to 34 in adult rats. BP follow-up was performed via photoelectric/oscillometric tail cuff method and intra-arterial BP was determined at 4, 8, 12 and 20 weeks of age or 34 and 38 weeks of age. Additionally, renal vascular resistance, albuminuria, renal inflammation and renal pathology were determined.. Up to 20 weeks of age, that is, 12 weeks after I3C withdrawal, mean arterial pressure (MAP) was significantly elevated in young I3C-treated rats (141 ± 7 mmHg) compared with controls (125 ± 6 mmHg). In adult rats, renin stimulation caused only a transient elevation in MAP, which returned to control values after I3C withdrawal. In young rats, the sustained pressor response was associated with increased indices of renal vascular resistance, glomerulosclerosis and tubulointerstitial damage as well as with a moderate inflammatory response. In adult rats, renal pathology and inflammation was significantly less than in young rats and was reversible.. Transient RAS stimulation causes sustained elevation in BP in young, but not in adult Cyp1a1-Ren2 transgenic rats and is associated with irreversible changes in renal structure and function and a moderate renal inflammatory response.

Topics: Age Factors; Animals; Arteries; Blood Pressure; Disease Models, Animal; Gene Expression; Glomerulosclerosis, Focal Segmental; Glycogen; Hypertension; Indoles; Kidney; Nephritis, Interstitial; Periodic Acid-Schiff Reaction; Rats; Rats, Transgenic; Receptors, Angiotensin; Renin; Renin-Angiotensin System

Fatty acids (FAs) are acquired from free FA associated with albumin and lipoprotein triglyceride that is hydrolyzed by lipoprotein lipase (LpL). Hypertrophied hearts shift their substrate usage pattern to more glucose and less FA. However, FAs may still be an important source of energy in hypertrophied hearts. The aim of this study was to examine the importance of LpL-derived FAs in hypertensive hypertrophied hearts. We followed cardiac function and metabolic changes during 2 wk of angiotensin II (ANG II)-induced hypertension in control and heart-specific lipoprotein lipase knockout (hLpL0) mice. Glucose metabolism was increased in ANG II-treated control (control/ANG II) hearts, raising it to the same level as hLpL0 hearts. FA uptake-related genes, CD36 and FATP1, were reduced in control/ANG II hearts to levels found in hLpL0 hearts. ANG II did not alter these metabolic genes in hLpL0 mice. LpL activity was preserved, and mitochondrial FA oxidation-related genes were not altered in control/ANG II hearts. In control/ANG II hearts, triglyceride stores were consumed and reached the same levels as in hLpL0/ANG II hearts. Intracellular ATP content was reduced only in hLpL0/ANG II hearts. Both ANG II and deoxycorticosterone acetate-salt induced hypertension caused heart failure only in hLpL0 mice. Our data suggest that LpL activity is required for normal cardiac metabolic compensation to hypertensive stress.

Topics: Adenosine Triphosphate; Angiotensin II; Animals; Blood Pressure; Cardiomegaly; Desoxycorticosterone; Fatty Acids; Glucose; Glycogen; Hypertension; Lipid Metabolism; Lipids; Lipoprotein Lipase; Mice; Mice, Knockout; Myocardium; Oxidation-Reduction; Protein Serine-Threonine Kinases; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Triglycerides

Chronic treatment of rats with N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) biosynthesis, results in hypertension mediated partly by enhanced angiotensin-I-converting enzyme (ACE) activity. We examined the influence of L-NAME on rat liver morphology, on hepatic glycogen, cholesterol, and triglyceride content, and on the activities of the cytochrome P450 isoforms CYP1A1/2, CYP2B1/2, CYP2C11, and CYP2E1. Male Wistar rats were treated with L-NAME (20 mg/rat per day via drinking water) for 2, 4, and 8 weeks, and their livers were then removed for analysis. Enzymatic induction was produced by treating rats with phenobarbital (to induce CYP2B1/2), beta-naphthoflavone (to induce CYP1A1/2), or pyrazole (to induce CYP2E1). L-NAME significantly elevated blood pressure; this was reversed by concomitant treatment with enalapril (ACE inhibitor) or losartan (angiotensin II AT(1) receptor antagonist). L-NAME caused vascular hypertrophy in hepatic arteries, with perivascular and interstitial fibrosis involving collagen deposition. Hepatic glycogen content also significantly increased. L-NAME did not affect fasting glucose levels but significantly reduced insulin levels and increased the insulin sensitivity of rats, based on an intraperitoneal glucose tolerance test. Immunoblotting experiments indicated enhanced phosphorylation of protein kinase B and of glycogen synthase kinase 3. All these changes were reversed by concomitant treatment with enalapril or losartan. L-NAME had no effect on hepatic cholesterol or triglyceride content or on the basal or drug-induced activities and protein expression of the cytochrome P450 isoforms. Thus, the chronic inhibition of NO biosynthesis produced hepatic morphological alterations and changes in glycogen metabolism mediated by the renin-angiotensin system. The increase in hepatic glycogen content probably resulted from enhanced glycogen synthase activity following the inhibition of glycogen synthase kinase 3 by phosphorylation.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Chronic Disease; Cytochrome P-450 Enzyme System; Enalapril; Enzyme Activation; Enzyme Inhibitors; Fasting; Glucose; Glycogen; Glycogen Synthase Kinase 3; Hypertension; Hypertrophy; Liver; Liver Cirrhosis; Losartan; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Peptidyl-Dipeptidase A; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Renin-Angiotensin System

Topics: Biological Transport; Erythrocyte Membrane; Glucose; Glycogen; Humans; Hyperinsulinism; Hypertension; Insulin; Insulin Resistance; Membrane Fluidity; Muscle, Skeletal

Compared with normal hearts, those with pathology (hypertrophy) are less tolerant of metabolic stresses such as ischemia. Pharmacologic intervention administered prior to such stress could provide significant protection. This study determined, firstly, whether the pentose sugar ribose, previously shown to improve postischemic recovery of energy stores and function, protects against ischemia when administered as a pretreatment. Secondly, the efficacy of this same pretreatment protocol was determined in hearts with pathology (hypertrophy). For study 1, Sprague-Dawley rats received equal volumes of either vehicle (bolus i.v. saline) or ribose (100 mg/kg) before global myocardial ischemia. In study 2, spontaneously hypertensive rats (SHR; blood pressure approximately 200/130) with myocardial hypertrophy underwent the same treatment protocol and assessments. In vivo left ventricular function was measured and myocardial metabolites and tolerance to ischemia were assessed. In normal hearts, ribose pretreatment significantly elevated the heart's energy stores (glycogen), and delayed the onset of irreversible ischemic injury by 25%. However, in vivo ventricular relaxation was reduced by 41% in the ribose group. In SHR, ribose pretreatment did not produce significant elevations in the heart's energy or improvements in tolerance to global ischemia, but significantly improved ventricular function (maximal rate of pressure rise (+dP/dt(max)), 25%; normalized contractility ((+dP/dt)/P), 13%) despite no change in hemodynamics. Thus, administration of ribose in advance of global myocardial ischemia does provide metabolic benefit in normal hearts. However, in hypertrophied hearts, ribose did not affect ischemic tolerance but improved ventricular function.

Topics: Adenosine Triphosphate; Anaerobic Threshold; Animals; Cardiotonic Agents; Disease Models, Animal; Drug Administration Schedule; Glycogen; Hypertension; Hypertrophy, Left Ventricular; Injections, Intravenous; Male; Myocardial Ischemia; Myocardium; Phosphocreatine; Rats; Rats, Sprague-Dawley; Ribose; Structure-Activity Relationship; Ventricular Function, Left; Ventricular Function, Right

In order to explore the possible effects of physical therapy interventions on people with hypertension, we evaluated the effects of aerobic exercise training on myocardial energy metabolism in an animal model of hypertension.. We used 36 female spontaneously hypertensive rats (rats with genetically induced hypertension) and 12 normotensive Wistar-Kyoto rats.. The normotensive rats were sedentary and formed the CONsed group. The spontaneously hypertensive rats were randomly divided into 3 experimental groups (12 rats per group). Hypertensive rats that were sedentary formed the HTNsed group, those that received 8 weeks of exercise training formed the HTNx8 group, and those that received 16 weeks of exercise training formed the HTNx16 group. We measured systolic blood pressure, heart wet weight, maximal activities of cardiac energy metabolism enzymes, glucose transporter content, and total concentrations of protein, glycogen, and triglyceride.. Systolic blood pressure was greater than 200 mm Hg in the CONsed group at the time of testing. Exercise training modestly (approximately 11-18 mm Hg) lowered blood pressure in the HTNx8 and HTNx16 groups. Fatty acid enzyme activity was greater in the CONsed group than in HTNsed and HTNx8 groups, but activity was roughly equivalent between the CONsed group and the HTNx16 group. Glucose enzyme activity was greater in the HTNx16 group than in the CONsed group and HTNsed group. Intracellular glycogen concentration was greater in the HTNx8 group than in HTNsed group.. Results of this study suggest that aerobic exercises may help to normalize cardiac energy metabolism in mammals with hypertension.

Topics: Animals; Blood Pressure; Carnitine O-Palmitoyltransferase; Citrate (si)-Synthase; Disease Models, Animal; Energy Metabolism; Female; Glycogen; Glycolysis; Hexokinase; Hypertension; Myocardium; Physical Conditioning, Animal; Physical Therapy Modalities; Random Allocation; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Systole

The aim of this study was to ascertain whether the presence of hypertension conveys a more severe degree of insulin resistance in type 2 diabetes mellitus and, if so, which biochemical pathways are involved. We quantitated the rates of total glucose disposal, glycogen synthesis (GS), glycolysis, glucose oxidation, endogenous glucose production, and LOX in the basal state and during a 4-h euglycemic ( approximately 5 mM) hyperinsulinemic ( approximately 300 pM) clamp carried out in combination with a dual-tracer infusion ([(3)H]-3- and [(14)C]-U-D-glucose) and indirect calorimetry in 42 nonobese noninsulin-treated type 2 diabetic subjects (22 hypertensive and 20 normotensive) and 23 nonobese nondiabetic subjects (9 without and 14 with essential hypertension). Compared with normotensive controls, both groups of diabetic subjects were markedly insulin resistant. In the basal state, all glucose fluxes were similar in diabetic subjects with or without hypertension. During insulin infusion, total glucose disposal was significantly reduced in hypertensive diabetic subjects, compared with their normotensive counterparts (18.7 +/- 1.0 vs. 28.6 +/- 3.0 micromol/min.kg lean body mass; P < 0.01). This difference was almost entirely explained by a marked reduction in GS (4.5 +/- 2.0 vs. 12.5 +/- 3.3 micromol/min.kg lean body mass; P < 0.01). Endogenous glucose production was not different in the two diabetic groups during insulin infusion and was significantly higher than in normotensive controls. Lipid oxidation was less suppressed by hyperinsulinemia in hypertensive than in normotensive diabetic subjects (1.46 +/- 0.1 vs. 0.91 +/- 0.1 micromol/min.kg lean body mass; P < 0.01). Glucose fluxes were not significantly different in nondiabetic subjects with essential hypertension and in normotensive diabetic individuals. These results indicate that hypertension markedly aggravates insulin resistance featuring type 2 diabetes mellitus. The molecular defects underlying this phenomenon involve primarily GS.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycogen; Humans; Hypertension; Insulin Resistance; Lipid Metabolism; Male; Middle Aged; Oxidation-Reduction

A subgroup of patients with type 2 diabetes shows a clustering of abnormalities such as peripheral insulin resistance, hypertension, and microalbuminuria. To evaluate whether these traits reflect intrinsic disorders of cell function rather than in vivo environmental effects, we studied a group of 7 nondiabetic hypertensive subjects with an altered albumin excretion rate (AER) (HyMA+) and 3 groups of patients with type 2 diabetes: 7 with normal blood pressure and normal AER (DH-MA-), 7 with high blood pressure and normal AER (DH+MA-), and 7 with both high blood pressure and altered AER (DH+MA+). Glucose disposal was measured during an hyperinsulinemic clamp (40 mU. m(2)(-1). min(-1)) with primed deuterated [6.6 (2)H(2)] glucose infusion. In the same subjects, a skin biopsy was performed and the following parameters were investigated: glucose transport (as determined by [(3)H]2-deoxyglucose uptake); glycogen synthase activity (as determined by [(14)C] glucose incorporation from UDP-[U-(14)C] glucose into glycogen); glycogen phosphorylase activity (as measured by the incorporation of [U-(14)C]glucose 1-phosphate into glycogen); and total glycogen content. In vivo glucose disposal was significantly reduced in DH+MA- and DH+MA+, with respect to DH-MA-, HyMA+, and controls. Insulin-stimulated glucose transport was similar in the 3 groups of patients with diabetes. A significant reduction of intracellular glycogen content was observed in DH+MA- and DH+MA+ compared with DH-MA- in both basal and insulin-stimulated conditions, probably because of a major impairment of glycogen synthase activity. Glycogen phosphorylase activity did not show differences between the groups. These results suggest that (1) the combination of type 2 diabetes with hypertension and altered AER is associated with impaired insulin sensitivity, and (2) intrinsic, possibly genetic, factors may account for increased peripheral insulin resistance in hypertensive microalbuminuric patients with type 2 diabetes, pointing to the reduction of glycogen synthase activity as a shared common defect.

Topics: Albuminuria; Cells, Cultured; Deoxyglucose; Diabetes Mellitus, Type 2; Female; Fibroblasts; Glucose; Glucose Clamp Technique; Glycogen; Glycogen Synthase; Humans; Hypertension; Insulin; Insulin Resistance; Liver; Male; Middle Aged

Abnormalities in glucose metabolism and insulin action are frequently detected in patients with essential hypertension. Spontaneously hypertensive rats (SHR) have been used as an experimental model to understand this pathological condition. The objective of the present study was to assess glucose metabolism and insulin action in SHR and Wistar rats under fed and fasting conditions. Peripheral glucose utilization was estimated by kinetic studies with [6-(3)H]-glucose and gluconeogenetic activity was measured during continuous [(14)C]-bicarbonate infusion. Plasma glucose levels were higher in the SHR group. Plasma insulin levels in the fed state were higher in the SHR group (99.8 +/- 6.5 microM) than in the control group (70.4 +/- 3.6 microM). Muscle glycogen content was reduced in SHR compared to control under the various experimental conditions. Peripheral glucose utilization was slightly lower in the SHR group in the fed state (8.72 +/- 0.55 vs 9.52 +/- 0.80 mg kg(-1) min(-1) in controls). Serum free fatty acid levels, hepatic glycogen levels, hepatic phosphoenolpyruvate carboxykinase activity and gluconeogenetic activity were similar in the two groups. The presence of hyperglycemia and hyperinsulinemia and the slightly reduced peripheral glucose utilization suggest the presence of resistance to the action of insulin in peripheral tissues of SHR. Hepatic gluconeogenesis does not seem to contribute to the metabolic alterations detected in these animals.

Topics: Animals; Glucose; Glycogen; Hyperglycemia; Hypertension; Male; Phosphoenolpyruvate Carboxykinase (ATP); Rats; Rats, Inbred SHR; Rats, Wistar

In a previous report, we observed an altered proportion of fiber types and a reduction of capillary per fiber ratio in extensor digitorus longus (EDL) and soleus (SOL) muscles of deoxicorticosterone acetate (DOCA)-salt hypertensive rats when compared with controls. The aim of the present study was to ascertain various carbohydrate and lipid enzyme activities and substrates that may be involved in the morphological changes reported. In the SOL muscle of hypertensive rats, glucose, glycogen and triglycerides (TG) levels were increased, citrate synthase (CS) and beta-hydroxy-acyl-CoA dehydrogenase (HAD) activities were reduced, while hexokinase (HK) and lipoprotein lipase (LPL), LPL mass, lactate and free fatty acids (FFA) levels were unchanged. In EDL muscles of hypertensive rats, glycogen levels and LPL mass were higher than in controls, while CS, HAD, HK, and LPL activities and glucose, lactate, FFA and TG levels were unmodified. Serum levels of insulin, TG, cholesterol and FFA were increased while glucose levels were decreased and high-density lipoprotein-cholesterol levels were similar in hypertensive rats when compared with controls. In conclusion, hypertensive rats showed increased glycogen in both EDL and SOL muscles, with hyperinsulinemia and reduced glycemia. Hyperinsulinemia might have been a compensatory response to insulin resistance. The oxidative capacity of SOL muscle was reduced indicating that glucose uptake was conduced via non-oxidative metabolism. TG, FFA and cholesterol were increased in serum and TG in SOL muscle.

Topics: 3-Hydroxyacyl CoA Dehydrogenases; Animals; Blood Glucose; Cholesterol; Citrate (si)-Synthase; Desoxycorticosterone; Fatty Acids, Nonesterified; Glucose; Glycogen; Hexokinase; Hypertension; Insulin; Lactic Acid; Lipoprotein Lipase; Muscle, Skeletal; Rats; Rats, Sprague-Dawley; Sodium Chloride; Triglycerides

The spontaneously hypertensive/NIH-corpulent (SHR/N-cp) rat is a genetic model that exhibits both non-insulin-dependent diabetes mellitus (NIDDM) and hypertension. To determine the impact of long-term treatment with the long-acting angiotensin-converting enzyme (ACE) inhibitor perindopril (PE) on the glucose metabolism, lipid levels, and heart in this model, studies were performed in three groups of SHR/N-cp rats maintained on a diet containing 54% carbohydrate with 18% sucrose and 36% starch. One group of obese rats received PE (0.5 to 1.0 mg/kg body weight/d) for 3 to 4 months, a second group of obese rats received no treatment, and a third group of lean rats were used as controls. The mean systolic blood pressure (SBP) increased gradually in both untreated obese and lean rats, with lean animals showing slightly higher levels compared with untreated obese rats. By contrast, SBP was reduced to normal levels in PE-treated obese rats throughout the treatment period. Compared with lean rats, obese rats showed significantly higher body weight and fasting serum levels of glucose, insulin, total cholesterol (TC), and triglyceride (TG). However, no significant differences were observed in these metabolic parameters between PE-treated and untreated obese rats. Plasma renin activity measured at the end of the treatment period was significantly higher in PE-treated rats compared with untreated obese and untreated lean rats. The mean heart weight and left ventricular weight, expressed in absolute terms or indexed to body weight, were significantly lower in PE-treated versus untreated obese and untreated lean rats. To further determine whether glucose metabolism is directly affected by PE treatment, in vitro glycogen synthesis was evaluated in isolated soleus muscles obtained from three additional groups of animals. The basal rate of muscle glycogen synthesis was significantly lower in obese compared with lean rats (P < .05), but did not differ between PE-treated and untreated obese rats. Maximal insulin-stimulated glycogen synthesis increased threefold in PE-treated obese rats, but this increase did not differ from the increases observed in untreated obese and lean rats. In conclusion, the present study shows that long-term PE treatment in obese SHR/N-cp rats with NIDDM and hypertension effectively controlled systemic arterial pressure and resulted in a significant reduction in left ventricular weight. However, these favorable effects of PE were not associated with

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Diabetes Mellitus, Type 2; Glycogen; Heart; Hypertension; Indoles; Male; Perindopril; Rats; Rats, Inbred SHR

The spontaneously hypertensive rat (SHR) has been reported to be insulin-resistant compared to the Wistar-Kyoto (WKY) parent strain. Because insulin resistance usually reflects a defect in insulin action at the muscle, we compared the ability of muscle (gastrocnemius) to store glycogen in response to a standard oral glucose challenge in SHR to that in WKY. As a control, we examined the glycogen response in liver in these two rat strains. However, in vivo insulin action reflects both tissue responsiveness as well as substrate and hormone availability at the tissue level. To evaluate tissue responsiveness in vitro, we examined two parameters of insulin action: 1) muscle glycogen synthesis using 3H-glucose and 2) muscle glucose transport using 3H-2-deoxy-glucose (3H-2-DG). Thirteen-week-old male rats were studied after overnight fasting. Liver glycogen increased similarly (mean +/- SD shown) in response to glucose gavage feeding in both groups [WKY: 15.2 +/- 6.9 to 50.6 +/- 17.9 micromol/g wet wt (P < .05); SHR: 30 +/- 18 to 63.5 +/- 33.3 micromol/g wet wt (P < .01)]. On the other hand, muscle glycogen increased in WKY [13.7 +/- 2 to 17.8 +/- 1.1 micromol/g wet wt (P < .05)], whereas in SHR there was no significant change [14.6 +/- 2.1 to 15.3 +/- 2.99 micromol/g wet wt P = NS)]. Results of in vitro studies demonstrated that glycogen synthesis increased from 377 +/- 120 to 439 +/- 175 disintegrations per minute (dpm) 3H-glucose/mg extensor digitorum longus (EDL) in WKY when insulin increased from 0 to 1000 microU/mL (P < .05), whereas SHR the increase was from 289 +/- 89 to 565 +/- 187 (P < .05). Glucose transport increased from 483 +/- 74 to 785 +/- 369 dpm 3H-2-DG/mg EDL in WKY when insulin was increased from 0 to 500 microU/mL (P < .03), whereas in SHR the increase was 516 +/- 61 to 997 +/- 347 (P < .001). In summary, liver glycogen increased in response to feeding in a similar manner in both WKY and SHR, whereas muscle glycogen increased only in WKY. We conclude that in vivo muscle glycogen accumulation may represent an index of insulin resistance in SHR. In contrast, in vitro data suggest that both muscle glucose transport and glycogen synthesis were stimulated to a comparable degree by insulin in EDL strips from WKY and SHR; there were no significant differences between WKY and SHR. Further studies are needed to clarify these differences.

Topics: Animals; Biological Transport; Glucose; Glycogen; Hypertension; In Vitro Techniques; Insulin; Insulin Resistance; Male; Muscle, Skeletal; Rats; Rats, Inbred SHR; Rats, Inbred WKY

Studies of the effect of sex on the metabolic state of rats with chronic hypertension and concomitant myocardial hypertrophy were conducted. Female and male spontaneously hypertensive rats (SHRs) with early myocardial hypertrophy (5.5 mo old) were used. Serum fatty acids, liver glycogen, and myocardial glycogen were measured at baseline and after the rats were deprived of food for 24 h. The metabolic effects of progressive myocardial hypertrophy in females were assessed in additional groups of female SHRs (5.5 or 12 mo old) under the following conditions: control, food deprived, or food deprived and refed with equienergetic lipid-rich (38.9% of total energy) or carbohydrate-rich (76.5% of total energy) diets. Despite no differences in serum fatty acids, females had significantly higher baseline myocardial glycogen and liver glycogen concentrations than males. In response to food deprivation, females continued to have significantly higher myocardial glycogen and fatty acid concentrations than males, whereas there were no sex differences in liver glycogen, which was depleted in both males and females. Older hypertensive females had higher baseline fatty acid concentrations and lower liver glycogen concentrations than younger females, whereas there were no differences in myocardial glycogen. Food deprivation doubled fatty acid concentrations, depleted liver glycogen, and increased myocardial glycogen in both age groups. In both age groups, fatty acid concentrations and liver glycogen did not return to baseline values after food deprivation and refeeding. In both age groups, fatty acid concentrations increased further after the lipid-rich diet whereas liver glycogen concentrations returned to approximately 50% of baseline values after the carbohydrate-rich diet. Refeeding with either diet did not significantly increase myocardial glycogen further. Thus, the metabolic response to dietary manipulation was influenced by both sex and, in females, progressive pathology.

Topics: Aging; Animals; Cardiomegaly; Diet; Fatty Acids; Female; Food Deprivation; Glycogen; Hypertension; Liver; Male; Rats; Rats, Inbred SHR; Sex Characteristics

Topics: Adipocytes; Animals; Cells, Cultured; Glucose; Glycogen; Hypertension; Insulin; Insulin Resistance; Lipids; Muscle, Skeletal; Organ Specificity; Rats; Rats, Inbred SHR; Rats, Inbred WKY

To explore the relationship between insulin resistance and hypertension, we examined whether acute induction of hypertension can engender insulin resistance. For this purpose we measured rates of insulin-mediated glucose uptake in awake unstressed rats with the euglycemic hyperinsulinemic (12 microns.kg-1.min-1) clamp technique during infusions of saline alone or after induction of hypertension by bolus administration of NG-monomethyl-L-arginine (L-NMMA, 30 and 15 mg/kg), a competitive inhibitor of nitric oxide synthase. Arterial pressure was approximately 20% greater with L-NMMA bolus than with saline alone. Isotopically determined steady-state rates of glucose uptake were 36 +/- 1 mg.kg-1.min-1 during saline alone and 26 +/- 2 and 19 +/- 1 mg.kg-1.min-1 with low- and high-dose L-NMMA (P < 0.001 vs. saline), respectively. To rule out that insulin resistance induced by L-NMMA was adrenergically mediated, clamp studies were repeated with alpha- and beta-blockade. Rates of glucose uptake remained approximately 20% below those observed with saline alone (P < 0.001). A significant inverse correlation was observed between the height of the blood pressure and the rate of glucose uptake (r = 0.32, P = 0.04). In conclusion, acute induction of hypertension with L-NMMA can cause marked insulin resistance. We postulate that reduced skeletal muscle perfusion and/or sympathetic nervous system activation may contribute to insulin resistance induced by L-NMMA.

Topics: Animals; Arginine; Blood Glucose; Glucose; Glycogen; Hypertension; Insulin; Insulin Resistance; Liver; Male; Muscle, Skeletal; Nitric Oxide Synthase; omega-N-Methylarginine; Osmolar Concentration; Rats; Rats, Sprague-Dawley

Several studies on both humans and animal models have reported a pathogenetic relationship among hyperinsulinism, insulin resistance, and hypertension. We have previously evaluated whole body glucose disposal and insulin sensitivity in different models of hypertensive rats, showing an increase rather than an impairment of glucose metabolism, which in turn was due to an improved ability of insulin to channel the absorbed glucose towards the nonoxidative disposal. Aiming to confirm our previous findings we performed the direct assay of skeletal muscle glycogen synthase on tissue samples from the previous clamp studies, as a rate limiting step enzyme of glycogen synthesis, under conditions of physiologic hyperinsulinemia and euglycemia. Glycogen synthase was assayed on samples from rectus muscle tissues of spontaneously hypertensive rats and high sodium, one kidney, one figure-8 hypertensive rats. Compared to controls, our data show an increased activity of glycogen synthase in the hypertensive animals, which is consistent with the increased glycogen synthesis previously reported. In conclusion, under our experimental conditions, hypertension and chronic hyperadrenergism are associated with an increased ability of insulin to stimulate glucose uptake and disposal. These latter effects are mainly due to an increase in nonoxidative disposal and glycogen synthase activity.

Topics: Animals; Disease Models, Animal; Glucose; Glycogen; Glycogen Synthase; Hypertension; Muscle, Skeletal; Rats; Rats, Inbred SHR; Rats, Inbred WKY

Angiotensin-converting enzyme (ACE) inhibitors can improve cardiac function independent of their blood pressure (BP)-lowering actions. We investigated the effect of chronic subantihypertensive ACE inhibitor treatment on functional and biochemical cardiac parameters in stroke-prone spontaneously hypertensive rats (SHRSP). Animals were treated in utero and subsequently to age 20 weeks with the ACE inhibitor perindopril (0.01 mg/kg/day). The contribution of endogenous bradykinin (BK) potentiation to the actions of the ACE inhibitor was assessed by cotreatment with the BK beta 2-receptor antagonist Hoe 140 (500 micrograms/kg/day subcutaneously, s.c.) from age 6 to 20 weeks and by measurement of myocardial prostacyclin and cyclic GMP concentrations. Chronic low-dose perindopril treatment had no effect on development of hypertension and left ventricular hypertrophy (LVH), but perindopril improved cardiac function, as demonstrated by increased LV pressure (LVP) (19.4%) and LVdp/dtmax (27.8%) but no change in heart rate (HR). The activities of lactate dehydrogenase (LDH) and creatine kinase (CK) as well as lactate concentrations in the coronary venous effluent were reduced by 39.3, 50, and 60.6%, respectively. Myocardial tissue concentrations of glycogen and the energy-rich phosphates ATP and CK were increased by 16.3, 33.1, and 28.2%, respectively. All ACE inhibitor-induced effects on cardiac function and metabolism were abolished by concomitant chronic BK receptor blockade. Cardiac prostacyclin concentrations were threefold elevated in perindopril-treated animals whereas cardiac cyclic GMP concentration remained unchanged as compared with that of controls. Our data demonstrate that chronic low-dose ACE inhibitor treatment can improve cardiac function and metabolism by potentiating endogenous BK.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Bradykinin; Cerebrovascular Disorders; Coronary Circulation; Creatine Kinase; Cyclic GMP; Disease Models, Animal; Glycogen; Heart; Heart Rate; Hypertension; Hypertrophy, Left Ventricular; Indoles; L-Lactate Dehydrogenase; Myocardium; Perindopril; Rats; Rats, Inbred SHR

The effect of chronic low- and high-dose treatment with the angiotensin-converting enzyme (ACE) inhibitor ramipril (0.01 and 1 mg/kg per day) on the development of hypertension and left ventricular hypertrophy as well as on functional and biochemical alterations of the heart was studied in stroke-prone spontaneously hypertensive rats treated prenatally and subsequently up to the age of 20 weeks. The contribution of endogenous bradykinin potentiation to the ACE inhibitor actions was assessed by cotreatment of rats with the bradykinin B2-receptor antagonist Hoe 140 (500 micrograms/kg per day SC) from 6 to 20 weeks of age. High- but not low-dose ACE inhibitor treatment prevented the development of hypertension and left ventricular hypertrophy. Chronic bradykinin receptor blockade did not attenuate the antihypertensive and antihypertrophic actions of ramipril. High-dose ramipril treatment improved cardiac function, as demonstrated by an increase in left ventricular pressure (29.9%), dP/dtmax (34.9%), and coronary flow (22.1%), without a change in heart rate. The activities of lactate dehydrogenase and creatine kinase and lactate concentration in the coronary effluent were reduced by 39.3%, 55.5%, and 66.7%, respectively. Myocardial tissue concentrations of glycogen and the energy-rich phosphates ATP and creatine phosphate were increased by 31.3%, 39.9%, and 73.7%, respectively, whereas lactate was decreased by 20.8%. Chronic low-dose ACE inhibitor treatment led to a pattern of changes in cardiodynamics and cardiac metabolism similar to that observed with the high dose. All ACE inhibitor-induced effects on cardiac function and metabolism were abolished by chronic bradykinin receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Administration, Oral; Animals; Bradykinin; Cerebrovascular Disorders; Coronary Circulation; Creatine Kinase; Dose-Response Relationship, Drug; Female; Glycogen; Heart; Hypertension; Hypertrophy, Left Ventricular; L-Lactate Dehydrogenase; Lactates; Male; Myocardium; Phosphocreatine; Pregnancy; Ramipril; Rats; Rats, Inbred SHR; Rats, Wistar; Ventricular Pressure

Forty spontaneously hypertensive rats (SHRs) and forty normotensive Wistar-ST rats (NRs) were used to assess the influence of anesthetics on myocardial and hepatic energy metabolism after hemorrhage. They were divided into five pairs of groups: a control group (pentobarbital 6 mg.100 g BW-1 ip), and four others which received 1.2% halothane, 2.2% enflurane, 1.4% isoflurane, and 3.3% sevoflurane, respectively. Following a 10 min stabilization period, blood (2 ml.100 g BW-1) was gradually withdrawn over a 5 min period from a femoral artery. Thirty min after the induction of hemorrhage, the heart and liver were removed and myocardial and hepatic metabolites (ATP, lactate, pyruvate and glycogen) were measured by enzymatic methods. There were no significant differences in myocardial metabolites among either the anesthetic groups or between SHRs and NRs. However, hepatic ATP levels in all SHR groups were significantly lower than those in NR groups. Moreover, ATP levels in the inhalation anesthetic groups of SHRs were significantly higher than that in the control group of SHRs. All inhalation anesthetics, especially isoflurane, may reduce metabolic deterioration of the liver during hemorrhage when compared to barbiturate anesthesia.

Topics: Adenosine Triphosphate; Alkalosis; Anesthesia, Inhalation; Anesthetics; Animals; Blood Pressure; Energy Metabolism; Enflurane; Ethers; Glycogen; Halothane; Heart; Hematocrit; Hemorrhage; Hypertension; Isoflurane; Lactates; Liver; Methyl Ethers; Myocardium; Pyruvates; Rats; Rats, Inbred SHR; Rats, Wistar; Sevoflurane

1. The relationship between hypertension, obesity, non-insulin-dependent diabetes mellitus and various parameters of glucose metabolism was studied. Lean and obese rats of the SHR/N-cp and LA/N-cp congenic strains were studied at four months of age. 2. Tritium and 14C-labeled glucoses were infused in one set of rats while tritiated water and 14C-labeled alanine were infused in a second group. 3. Glucose oxidation, turnover, conversion to glycogen, fatty acid synthesis, and alanine conversion to glucose were determined, as were blood pressure, pulse pressure and heart rate. 4. The presence of obesity influenced body weight, body fat, de novo fatty acid synthesis, organ weights, glucose mass, glucose oxidation, glucose synthesis, glucose carbon turnover and pulse pressure. 5. It had no effect on glycogen synthesis, tissue glycogen levels, blood glucose, glucose space, or blood pressure. 6. Strain differences were observed in final body weight, organ weights, blood pressure, pulse pressure, hepatic fatty acid synthesis, glucose mass, glucose space, glucose synthesis, liver glycogen levels and glucose conversion to muscle glycogen. 7. Strain-phenotype interaction effects were observed on glucose incorporation into hepatic glycogen, Cori cycle activity, hepatic de novo fatty acid synthesis, final body weight, fat pad weight, heart weight, and mean arterial pressure. 8. These results suggest that although obesity and hypertension are genetic traits in these rats, these traits are independent in their influence on the metabolism of glucose and the development of non-insulin-dependent diabetes mellitus.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Disease Models, Animal; Fatty Acids; Glucose; Glycogen; Hemodynamics; Hypertension; Liver; Male; Muscles; Obesity; Organ Size; Rats; Rats, Inbred SHR

We investigated the preventive effects of long-term treatment with the angiotensin converting enzyme inhibitor ramipril on myocardial left ventricular hypertrophy and capillary length density in spontaneously hypertensive rats. Rats were treated in utero and subsequently up to 20 weeks of age with a high dose (1 mg/kg per day) or with a low dose (0.01 mg/kg per day) of ramipril. Animals given a high dose of ramipril remained normotensive, whereas those given a low dose developed hypertension in parallel to vehicle-treated controls. At the end of the treatment period, converting enzyme activity in heart tissue was inhibited dose-dependently in the treated groups. Both groups revealed an increase in myocardial capillary length density together with increased myocardial glycogen and reduced citric acid concentrations. Left ventricular mass was reduced only in high dose- but not in low dose-treated animals. Our results demonstrate that early onset treatment with a converting enzyme inhibitor can induce myocardial capillary proliferation, even at doses too low to antagonize the development of hypertension or left ventricular hypertrophy. We hypothesize that potentiation of kinins is responsible for this effect, probably by augmenting myocardial blood flow, which is a well-known trigger mechanism of angiogenesis in the heart.

Topics: Administration, Oral; Age Factors; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Animals; Animals, Newborn; Cardiomyopathy, Hypertrophic; Citrates; Citric Acid; Coronary Vessels; Dose-Response Relationship, Drug; Female; Glycogen; Hypertension; Hypertrophy; Maternal-Fetal Exchange; Microscopy, Electron; Myocardium; Peptidyl-Dipeptidase A; Pregnancy; Ramipril; Rats; Rats, Inbred SHR

We have assessed the in vivo activity of the Na(+)-H+ antiporter skeletal muscle in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) controls using phosphorus (31P) nuclear magnetic resonance spectroscopy to measure changes in cytosolic acid concentrations during isometric contraction. During contraction there was a small rate of rise in skeletal muscle cytosolic acid concentration to a smaller maximum concentration in SHR. This difference in acid response was removed by amiloride and was not attributable to differences in cell buffering or the rate of production of lactic acid, suggesting that the difference in acid response in SHR skeletal muscle is due to increased in vivo Na(+)-H+ antiporter activity. Amiloride reduced resting muscle glycogen concentration and increased muscle lactate concentration in the SHR. This could be related to altered in vivo calcium metabolism. The maximum tension produced by skeletal muscle during contraction in SHR was less than in WKY rats, and relaxation between twitches was significantly greater, consistent with the finding of increased vascular smooth muscle relaxation in essential hypertension. Since increased Na(+)-H+ antiporter activity occurs in association with increased relaxation of both skeletal and vascular smooth muscle, these data are not consistent with a relationship between increased Na(+)-H+ antiporter activity and increased maximal muscle tension development. However, they show that increase Na(+)-H+ antiporter activity is associated with increased muscle relaxation.

Topics: Amiloride; Animals; Carrier Proteins; Cytosol; Glycogen; Hypertension; Isometric Contraction; Lactates; Lactic Acid; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sodium-Hydrogen Exchangers

The present study was performed to investigate as to whether peripheral insulin resistance exists in spontaneously hypertensive rats (SHR). After a 12 h fasting period, SHR had significantly higher serum glucose and higher plasma glucagon values in comparison to normotensive control rats (WKY). There was a tendency for higher serum insulin concentrations as well, but this difference did not reach significance. After oral glucose loading or glucose/insulin administration, serum glucose and insulin levels were also higher in SHR compared to WKY rats. Muscle glycogen and glucose concentrations were identical in fasted SHR and WKY rats. With an oral glucose load or glucose/insulin treatment there was a significant increase in muscle glycogen, whereas glucose values declined in skeletal muscle. Both total (a+b-form) phosphorylase activity as well as the active a-form of the enzyme were similar in skeletal muscle of SHR and WKY rats. Glucose/insulin administration or oral glucose loading induced a considerable reduction of both a+b-form and a-form activities. The decrease in muscle phosphorylase activities was almost identical in both groups of animals. There was also a comparable activity of muscle glycogen synthetase activity in all groups of rats. Despite subtile changes of glucose, glucagon and to a lesser degree insulin levels which would be suggestive of insulin resistance, the data obtained from skeletal muscle argue against peripheral insulin resistance in spontaneously hypertensive rats.

Topics: Animals; Blood Glucose; Glycogen; Glycogen Synthase; Hypertension; Insulin; Insulin Resistance; Male; Muscles; Phosphorylases; Rats; Rats, Inbred SHR; Rats, Inbred WKY

The purpose of this study was to determine whether repeated exposure to high sustained +Gz (HS + Gz) stress induced persistent changes in the functional state of the cardiovascular system. Three groups of rabbits--centrifuged, restrained, and control--were studied. After being placed in the restraining system of the centrifuge, the animals were submitted three times in a row to 8-9 +Gz sustained for 40 s. This exposure was repeated three times a week for 3-6 weeks. Restrained animals were not exposed to HS + Gz. Control animals were not restrained. The two types of stress (centrifuge + restraint; restraint alone) determined the appearance of two types of arterial hypertension. Systolic arterial pressure (AP) and left ventricular pressure (LVP) significantly increased in restrained animals. The function of the cardiovascular system was more perturbed in centrifuged rabbits since the significant changes affected not only systolic AP and LVP but alos systemic diastolic AP and the maximum rate of rise of LVP. The myocardium of rabbits repeatedly subjected to HS + Gz exposures, except for those that suffered a fracture of the lumbar spine, was significantly glycogen-depleted.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Aerospace Medicine; Animals; Blood Pressure; Glycogen; Gravitation; Heart Rate; Hypertension; Male; Myocardial Contraction; Myocardium; Phosphocreatine; Rabbits

The metabolic effects of beta-adrenoceptor blocking agents during hypoglycaemia in patients prone to hypoglycaemia are of interest as diabetics are often treated with these drugs because of hypertension or angina pectoris. Compared with non-diabetics these patients also have impaired glucose compensation after hypoglycaemia, partly secondary to deficient release of glucagon. This makes the diabetics more dependent on adrenergic mechanisms to recover from low blood glucose concentrations. Non-selective beta-adrenoceptor blockade (propranolol) significantly impairs the glucose recovery rate after hypoglycaemia in insulin dependent diabetics, whereas selective beta-adrenoceptor blockade (metoprolol) does not have this side effect. The mechanism of the effect of propranolol is probably an attenuation of the gluconeogenesis secondary to deficient release of the important gluconeogenic substrates lactate and glycerol.

Topics: Adrenergic beta-Antagonists; Blood Glucose; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Glucagon; Gluconeogenesis; Glycerol; Glycogen; Humans; Hypertension; Hypoglycemia; Insulin; Lactates; Lactic Acid; Liver; Metoprolol; Propranolol

Topics: Adult; Aortic Diseases; Arteriosclerosis; Capillaries; Coronary Disease; Glycerolphosphate Dehydrogenase; Glycogen; Glycolysis; Humans; Hypertension; L-Lactate Dehydrogenase; Middle Aged; Periodontium

Muscle biopsies from the vastus muscle were taken at rest and immediately after upright bicycle exercise at 50% of the individual VO2max, before and during 6 wk of alprenolol treatment (200 to 400 mg twice daily) in 6 untrained patients with essential hypertension. Resting muscle concentrations (mmole - kg-1 - wet weight) of glycogen, glucose, lactate, and high-energy phosphates [adenosine triphosphate (ATP) and creatine phosphate (CP)] were not affected by alprenolol treatment, but after 10 min after exercise the glycogenolysis increased and depletion of ATP and CP was enhanced. The relationship between blood and muscle lactate was altered by alprenolol, indicating that alprenolol prevents lactate translocation from the muscle to the blood. The results show that during moderate exercise, leg muscle metabolism is influenced by long-term antihypertensive therapy.

Topics: Adenosine Triphosphate; Adult; Alprenolol; Blood Pressure; Glucose; Glycogen; Heart Rate; Humans; Hypertension; Lactates; Male; Muscles; Phosphocreatine; Physical Exertion

Spontaneously hypertensive rats and normotensive Kyoto Wistar controls were divided into 3 groups of 10 animals each and treated with phenoxybenzamine (5 mg/kg once daily), propranolol (25 mg/kg twice daily) or saline (once daily). After 5 weeks the in vitro incorporation of D-[U-14C]-glucose into aortic lipids and glycogen was measured in the presence and absence of insulin (1 mU/ml). In both normotensive and hypertensive rats treated with propranolol 14C-incorporation into triglycerides was reduced. Furthermore, insulin significantly stimulated 14C-incorporation into triglycerides, phospholipids and glycogen in propranolol-treated hypertensive rats. This effect was not statistically significant (0.05 less than p less than 0.1) in propranolol-treated normotensives. Phenoxybenzamine treatment did not significantly modify aortic lipogenesis or glycogen synthesis from glucose. Chronic propranolol treatment of spontaneously hypertensive rats resulted in aortic tissue becoming sensitized to insulin. Possible mechanisms and explanations for this are discussed.

Topics: Animals; Aorta; Blood Pressure; Body Weight; Chromatography, Thin Layer; Drug Interactions; Glucose; Glycogen; Hypertension; In Vitro Techniques; Insulin; Male; Phospholipids; Propranolol; Rats; Receptors, Adrenergic; Triglycerides

In order to study if rapid elevation of blood pressure is associated with cerebral ischemia, anesthetized (70% N2O) and artificially ventilated rats were subjected to angiotensin-induced hypertension. After a 5 min hypertensive period, cerebral cortex tissue was frozen in situ for subsequent measurements of labile glycolytic metabolites, ammonia, and organic phosphates. The degree of hypertension induced, which gave evidence of blood-brain barrier damage in 7 of 8 rats, did not affect the tissue concentrations of labile metabolites. It is concluded that ischemia does not contribute to the barrier damage, nor is it likely to be the cause of the clinical symptoms that may occur in conscious rats in the same experimental model.

Topics: Acute Disease; Ammonia; Angiotensin II; Animals; Blood-Brain Barrier; Brain; Energy Metabolism; Glucose; Glycogen; Hypertension; Ischemic Attack, Transient; Male; Organophosphorus Compounds; Rats; Rats, Inbred Strains

Topics: Animals; Blood Pressure; Cyclic AMP; Glucagon; Glycerol; Glycogen; Heart; Hypertension; In Vitro Techniques; Isoproterenol; Male; Myocardium; Phosphoric Diester Hydrolases; Rats; Rats, Inbred Strains; Time Factors

Topics: Adult; Aged; Aging; Cataract; Cytoplasm; Diabetes Mellitus; Epithelium; Female; Glaucoma; Glycogen; Humans; Hypertension; Iris; Male; Melanins; Microscopy, Electron; Middle Aged; Pigments, Biological

Topics: Adrenergic beta-Antagonists; Animals; Arrhythmias, Cardiac; Cardiovascular System; Digestive System; Glycogen; Heart Failure; Hemodynamics; Humans; Hypertension; Lipid Metabolism; Lung; Myocardial Infarction; Spleen; Sympatholytics

Topics: Acid Phosphatase; Alkaline Phosphatase; Capillaries; Coronary Disease; Coronary Vessels; Dihydrolipoamide Dehydrogenase; Electron Transport Complex IV; Esterases; Glycogen; Heart Conduction System; Heart Neoplasms; Histocytochemistry; Humans; Hypertension; Lipase; Methods; Myocardial Infarction; NAD; NADP; Regional Blood Flow; Succinate Dehydrogenase

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Chlorides; Electron Transport Complex IV; Esterases; Female; Glucose-6-Phosphatase; Glucuronidase; Glycogen; Histocytochemistry; Hypertension; Methacholine Compounds; Microscopy, Electron; Monoamine Oxidase; Potassium; Rats; Sodium; Succinate Dehydrogenase; Sweat Glands; Sweating; Uremia

Topics: Adenosine Triphosphate; Adrenalectomy; Animals; Bradycardia; Catecholamines; Epinephrine; Glycogen; Hypertension; Hypoxia; Lactates; Methods; Myocardium; Nitrogen; Phosphocreatine; Rabbits; Statistics as Topic; Sympatholytics

Topics: Diabetes Insipidus; Diuretics; Edema; Glycogen; Humans; Hypertension; Kidney Tubules

Topics: Glycogen; Humans; Hypertension; Kidney Diseases

Topics: Animals; Brain; Carbohydrate Metabolism; Central Nervous System; Conditioning, Classical; Dogs; Glycogen; Hypertension; Reflex

Topics: Glycogen; Glycogen Storage Disease; Humans; Hypertension; Medical Records; Prognosis

Topics: Electrocardiography; Glycogen; Glycogenolysis; Hypertension; Myocardium; Phosphorus; Phosphorus Compounds