Cardiac Hypertrophy Index Research Articles

Zofenopril exerts a cardiovascular protective effect on rats infused with angiotensin II beyond angiotensin-converting enzyme inhibition.

Elevated levels of angiotensin II are implicated in the hypertensive pathophysiological process. Zofenopril has a sulphydryl group which gives it antioxidant properties. The aim of this study was to investigate its beneficial effects beyond angiotensin-converting enzyme (ACE) inhibition using angiotensin II-infused rats as hypertension model. Zofenopril was added in drinking water. Systolic blood pressure was assessed by the tail-cuff method. Left ventricular weight/body weight ratio was calculated as cardiac hypertrophy index. An estimate of the cardiac collagen was performed by measuring the content of hydroxyproline. Vascular reactivity was evaluated on aortic rings and isolated perfused kidney, and vascular structure in thoracic aorta was studied. Superoxide anion generation was quantified in aorta by lucigenin-enhanced chemiluminescence. Zofenopril partially prevented the increase in systolic blood pressure and cardiac hypertrophy induced by angiotensin II and avoided the increase in collagen deposition. The treatment improved vasorelaxing responses, reversed the vascular remodelling and abolished the effects of angiotensin II on the production of ·O2-. It is worth to mention that all these results are observed even with high levels of plasma angiotensin. Zofenopril could exert additional beneficial effects beyond ACE inhibition that would justify the improvement of pathophysiological processes triggered by angiotensin II.

Exercise preconditioning attenuates pressure overload-induced pathological cardiac hypertrophy: potential role of HSF1 and NF-κB p65 signaling

To observe the effect of exercise preconditioning (EP) on pressure overload-induced pathological cardiac hypertrophy and explore related mechanisms. Ten-week-old male Sprague-Dawley rats (n = 80) were randomly divided into four groups via random number table method: sham, TAC, EP + sham and EP + TAC. Two EP groups were subjected to 4 weeks of treadmill training, and followed by sham and TAC operations. Eight weeks after the surgery, mean arterial pressure (MAP), cardiac morphology, mRNA expressions of the B-type natriuretic peptide (BNP) and heat shock protein (HSP) 70 and protein expression of the BNP, heat shock transcription factor 1 (HSF1), HSP70, nuclear factor κB (NF-κB) p65, and interleukin-2 (IL-2) were examined. (1) Pathological cardiac hypertrophy index: eight weeks after TAC, MAP, heart size, HW/BW, cross-sectional area of the cardiomyocytes (CSA) and mRNA and protein expressions of BNP in the LV were all significantly higher in the TAC and EP + TAC groups than respective sham groups (all P < 0.05). HW/BW, CSA, and mRNA and protein expressions of BNP in the LV were significantly lower in EP + TAC group than in TAC group (all P < 0.05). (2) mRNA and protein expressions of HSF1 and HSP70 and nuclear HSF1 levels were significantly downregulated post TAC, however, EP treatment significantly increased the expression of HSF1 and nuclear HSF1 levels in TAC rats (all P < 0.05). (3) mRNA and protein expressions of NF-κB p65 and IL-2 were significantly increased in the TAC and EP + TAC groups compared with the respective sham groups (all P < 0.05), which were significantly downregulated in EP + TAC group compared to TAC group (all P < 0.05). EP could effectively reduce the cardiac hypertrophic responses induced by TAC possibly through upregulating the expressions of HSF1 and HSP70 and inhibiting the expression of NF-κB p65 and its nuclear translocation.

Cardioprotective effects of magnesium valproate in type 2 diabetes mellitus

We have evaluated the effect of magnesium valproate (210mg/kg/day, p.o.) in type 2 diabetes induced cardiovascular complications induced by streptozotocin (STZ, 90mg/kg, i.p.) in neonatal wistar rats. Various biochemical, cardiovascular and hemodynamic parameters were measured at the end of 8 weeks of treatment. STZ produced significant hyperglycaemia, hypoinsulinemia and dyslipidemia, which was prevented by magnesium valproate treatment. STZ produced increase in Creatinine Kinase, C-reactive protein and lactate dehydrogenase levels and treatment with magnesium valproate produced reduction in these levels. STZ produced increase in cardiac and LV hypertrophy index, LV/RV ratio, LV collagen deposition and LV cardiomyocyte diameter which were decreased by magnesium valproate treatment. Magnesium valproate also prevented STZ induced hemodynamic alterations and oxidative stress. These results were further supported by histopathological studies in which magnesium valproate showed marked reduction in fibrosis and cardiac fiber disarray. In conclusion, our data suggests that magnesium valproate is beneficial as an anti-diabetic agent in type-2 diabetes mellitus and also prevents its cardiac complications.

Evaluation of Buspirone on Streptozotocin Induced Type 1 Diabetes and Its Associated Complications

We have evaluated the effect of buspirone (1.5 mg/kg/day, p.o.) type 1 diabetes induced cardiovascular complications induced by streptozotocin (STZ, 45 mg/kg, i.v.) in Wistar rats. Various biochemical, cardiovascular, and hemodynamic parameters were measured at the end of 8 weeks of treatment. STZ produced significant hyperglycaemia, hypoinsulinemia, and dyslipidemia, which was prevented by buspirone treatment. STZ produced increase in serum creatinine, urea, lactate dehydrogenase, creatinine kinase, and C-reactive protein levels and treatment with buspirone produced reduction in these levels. STZ produced increase in cardiac and LV hypertrophy index, LV/RV ratio, and LV collagen, which were decreased by buspirone treatment. Buspirone also prevented STZ induced hemodynamic alterations and oxidative stress. These results were further supported by histopathological studies in which buspirone showed marked reduction in fibrosis and cardiac fiber disarray. In conclusion, our data suggests that buspirone is beneficial as an antidiabetic agent in type 1 diabetes mellitus and also prevents its cardiac complications.

An orally active angiotensin-(1–7) inclusion compound and exercise training produce similar cardiovascular effects in spontaneously hypertensive rats

Low angiotensin-(1–7) (Ang-(1–7)) concentration is observed in some cardiovascular diseases and exercise training seems to restore its concentration in the heart. Recently, a novel formulation of an orally active Ang-(1–7) included in hydroxy-propyl-beta-cyclodextrin (HPB-CD) was developed and chronically administered in experimental models of cardiovascular diseases. The present study examined whether chronic administration of HPB-CD/Ang-(1–7) produces beneficial cardiovascular effects in spontaneously hypertensive rats (SHR), as well as to compare the results obtained with those produced by exercise training. Male SHR (15-week old) were divided in control (tap water) or treated with HPB-CD/Ang-(1–7) (corresponding to 30μgkg−1day−1 of Ang-(1–7)) by gavage, concomitantly or not to exercise training (treadmill, 10 weeks). After chronic treatment, hemodynamic, morphometric and molecular analysis in the heart were performed. Chronic HPB-CD/Ang-(1–7) decreased arterial blood pressure (BP) and heart rate in SHR. The inclusion compound significantly improved left ventricular (LV) end-diastolic pressure, restored the maximum and minimum derivatives (dP/dT) and decreased cardiac hypertrophy index in SHR. Chronic treatment improved autonomic control by attenuating sympathetic modulation on heart and vessels and the SAP variability, as well as increasing parasympathetic modulation and HR variability. Overall results were similar to those obtained with exercise training. These results show that chronic treatment with the HPB-CD/Ang-(1–7) inclusion compound produced beneficial effects in SHR resembling the ones produced by exercise training. This observation reinforces the potential cardiovascular therapeutic effect of this novel peptide formulation.

Abstract 392: Blood Pressure Variability: An Independent Marker to Morbimortality

Introdution: The purpose of this study was to investigate the mechanisms enrolled in the relationship between increased BP variability, heart damage and mortality in different pathophysiological conditions as hypertension, heart failure and myocardial infarction. Method: Wistar rats were divided into control and S (n=10, 8weeks). Sinoaortic denervation (S) was performed using the method previously described. BP and HR were analysed using a data acquisition system. BP variability was analyzed by spectral analysis. Left ventricle systolic ejection and diastolic isovolumetric relaxation time were evaluated by echocardiography. Cardiac fibrosis and cardiomyocytes diameter were quantified by histological analysis. CO, cardiac blood flow and cardiac index were evaluated using colored microspheres. Result: No difference was observed in BP and HR (C:104±2 vs 106±2 mmHg; C:313±7 vs 329±3 bpm), while BP variability was increased after S (C:29±2 vs 46*±5 mmHg). Left ventricle systolic ejection was decreased (C:72±0.9 vs 64*±1.5%) and diastolic isovolumetric relaxation time (C:21±1 vs 35*±1 ms) was increased in S group. Moreover, it was observed a reduction in CO (C:111±5 vs 81*±5 mL/min), an increase in cardiac resistance (C:35±1.8 vs 66*±2.6 mL/min/mmHg) and a decreased in cardiac index (C:320±9.7 vs 270*±8.1 l/min/m2) in S group. Those alterations resulted in decreased myocardial blood flow (C:3.47±0.21 vs 1.6*±0.3 mL/min/g). An increased cardiomyocytes diameter (C:14.9±0.3 vs 18.9*±0.3μm),fibrosis (C:0.85±0.08 vs 3.28*±0.2%) and cardiac hypertrophy index (C:3.07±0.06 vs 3.97*±0.1) were observed in S group.The association of all those changes lead to a 72% higher mortality in animals with increased blood pressure variability.(*p&lt;0.03) Conclusion: An increased BP variability resulted in a reduced cardiac blood flow, CO and cardiac index and an increased in myocardial resistance this adaptations occours as a attempt to homeostasis maintenance. Howerer, the morphofunctional alterations showed a diastolic dysfunction, increased cardiac hypertrophy index and fibrosis as a resulted. These adjustements could be a determinant factor in cardiac damage and in mortality in different pathological conditions, independently of BP levels.

Papel de la quinasa regulada por suero y glucocorticoides 1 en las alteraciones cardiacas producidas por la aldosterona en ratas

IntroductionAldosterone induces cardiac hypertrophy and it is known to induce serum and glucocorticoid regulated kinase 1 (SGK-1) gene expression. AimWe aimed to evaluate structural, functional, inflammatory and oxidative alterations, as well as serum and glucocorticoid regulated kinase1 (SGK-1) expression, produced in rat heart by aldosterone+salt administration. Treatment with spironolactone was evaluated to prove mineralocorticoids mediation. Matherial and methodsMale Wistar rats received aldosterone (1mg/kg/day)+1% NaCl for 3 weeks. Half of the animals were treated with spironolactone (200mg/kg/day). At the end of treatment hemodynamics were measured: SBP, DBP, LVEDP, LVSP, +dP/dt and –dP/dt. Heart relative weight was measured as cardiac hypertrophy index. mRNA expression of TGF-β, CTGF, MMP2, TIMP2, TNF-α,IL-1β, p22phox, eNOS and SGK-1 were measured. Cardiac collagen content was measured by histological techniques. ResultsSBP and DBP, LVSP and LVEDP were elevated (P<.05) in aldosterone+salt-treated rats. –dP/dt decreased (P<.05) in aldosterone+salt-treated rats, but +dP/dt was similar in all groups. Spironolactone normalized (P<.05) SBP, DBP, LVSP, LVEDP and –dP/dt. Relative heart weight, collagen content, mRNA expression of TGF-β, CTGF, MMP2, TIMP2, TNF-α, IL-1β, p22phox, eNOS and SGK-1 were increased (P<.05) in aldosterone+salt-treated rats, being reduced by spironolactone (P<.05). ConlusionsSGK-1 might be a key mediator in the structural, functional and molecular cardiac alterations induced by aldosterone+salt in rats. All the observed changes and mediators are related with activation of mineralocorticoid receptors.

Perindopril protects against streptozotocin-induced hyperglycemic myocardial damage/alterations

High blood pressure, obesity, abnormal lipid profile, which often coexist with diabetes, tend to be associated with preclinical cardiovascular abnormalities and may contribute to the association of diabetes with cardiovascular events. Many studies have proved that streptozotocin (STZ) is responsible for type-2-diabetes-induced cardiovascular complications. Long-term perindopril therapy in patients with hypertension and diabetes has been observed to correct carotid remodeling by reducing hypertrophy. We studied the effect of perindopril (1 mg/kg/d orally [po]) on cardiovascular complications in neonatal model of rats, which was induced by administering STZ (90 mg/kg, intraperitoneally [ip]), in 5-d-old wistar rats and cardiac hypertrophy induced by isoprenaline (ISO; 5 mg/kg, ip) for 10 d. Various biochemical, cardiac, and hemodynamic parameters were measured at the end of 8 weeks of treatment in diabetes model and 10 d in hypertrophy model. STZ produced hyperglycemia, hyperinsulinemia, dyslipidemia, hypertension, bradycardia, increased creatinine kinase (CK-MB), lactate dehydrogenase enzymes (LDH) and C-reactive protein (CRP) levels, cardiac hypertrophy, and oxidative stress. Chronic treatment with perindopril significantly prevented STZ-induced hyperglycemia and hyperinsulinemia and controlled dyslipdemia in diabetic rats. Further, perindopril produced a significant reduction in elevated levels of CRP, LDH, and CK. STZ-induced hypertension and bradycardia were also prevented by perindopril treatment. Perindopril also produced beneficial effect by preventing cardiac hypertrophy as evident from cardiac hypertrophy index and left ventricular hypertrophic index. Perindopril also prevented STZ-induced oxidative stress. Similar results were obtained in ISO-induced cardiac hypertrophic model, which confirms the beneficial role of perindopril in cardiac hypertrophy. In conclusion, our data from both studies suggest that perindopril produced beneficial effect on cardiac complications.

Benefi cial role of spironolactone, telmisartan and their combination on isoproterenol-induced cardiac hypertrophy

Introduction Although spironolactone and telmisartan are reported to reduce the risk of morbidity and death, direct studies on their eff ects on isoproterenol-induced cardiac hypertrophy are scanty. Hence the present investigation was carried out to study the eff ect of spironolactone, telmisartan and their combination on isoproterenol-induced cardiac hypertrophy.Methods Isoproterenol was administered intra-peritoneally in a dose of 5 mg/kg once daily for 10 days to Wistar rats. Spironolactone (20 mg/kg/day) (SL), telmisartan (5 mg/kg/day) (TM) or their combination (SLTM) was administered for 10 days after which various biochemical and cardiac parameters were measured.Results Isoproterenol produced dyslipidaemia, hypertension, elevated cardiac enzyme and C-reactive protein levels (CRP), worsened haemodynamic parameters and produced cardiac hypertrophy, left ventricular (LV) hypertrophy and oxidative stress. Chronic treatment with SL, TM or SLTM signifi cantly controlled dyslipidaemia and produced a signifi cant reduction in the elevated creatine-kinase (CK) and CRP levels. TM or SLTM produced a decrease in elevated lactate de-hydrogenase levels; however, SL failed to produce this eff ect. Hypotension, tachycardia, and decreased rate of pressure development and decay were prevented by SL, TM and SLTM treatment. Chronic treatment with SL, TM or SLTM also produced signifi cant reduction in LV collagen levels, cardiac and LV hypertrophy index and prevented oxidative stress.Conclusions Our data suggests that SL, TM and SLTM produced a benefi cial eff ect on cardiac hypertrophy.

Antioxidant Protective Effects of the Resveratrol on the Cardiac and Vascular Tissues from Renal Hypertensive Rats

Background: Accumulating reactive oxygen species (ROS) is involved in cellular signaling and function disturbances due to the oxidative stress, which contributes to several diseases. The consequences of ROS activity represent an im-portant mechanism on the pathogenesis of vascular diseases, such as hypertension. Increased blood pressure observed in renal hypertension of the 2 kidneys-1 clip (2K-1C) model involves increased ROS levels in the cardiovascular system. Resveratrol, a polyphenolic compound primarily found in red wine, has many biological and pharmacological proper-ties. Considering the antioxidant properties of resveratrol, the present study was aimed to investigate the effects of the chronic treatment with resveratrol on cardiovascular system from renal hypertensive rats. Results: 2K-1C hypertension presented increased blood pressure, which was reduced at the end of the fifth week of resveratrol treatment. The cardiac hypertrophy index and the basal levels of ROS in rat aortic rings were also reduced by resveratrol treatment. Conclusions: The present findings clearly show the protective effects from resveratrol on the blood pressure, the car-diac growth and the vascular ROS generation in renal hypertension.

Beneficial role of telmisartan on cardiovascular complications associated with STZ-induced type 2 diabetes in rats

We studied the effect of an eight-week treatment with telmisartan (5mg kg–1day–1) on cardiovascular complications that are associated with type 2 diabetes in a neonatal rat model. Type 2 diabetes was induced by the administration of 90mg/kg streptozotocin (STZ), ip, in two-day-old rats. The development of diabetes was checked 12 weeks after STZ administration, and the animals were divided into different groups. Telmisartan treatment was given for eight weeks. At the end of the eight-week treatment, various biochemical and cardiac parameters were measured. Diabetic rats exhibited hyperglycemia, hyperinsulinemia, hyperlipidemia, increased blood pressure and heart rate, increased creatinine, cardiac enzyme and C-reactive protein (CRP) levels, a reduction in the rate of pressure development and decay, cardiac hypertrophy and oxidative stress. Chronic treatment with telmisartan significantly prevented STZ-induced hypertension and tachycardia and elevated fasting glucose and insulin levels. It significantly prevented the dyslipidemia and significantly reduced the elevated creatinine and CRP levels and the levels of other cardiac enzyme markers, like lactate dehydrogenase and creatinine kinase, in diabetic rats. There was an increase in rate of blood pressure development and decay with telmisartan treatment. Telmisartan also produced beneficial effects by preventing cardiac hypertrophy, which was evident from left ventricular collagen levels, the cardiac hypertrophy index and the left ventricular hypertrophy index in diabetic rats. Telmisartan successfully prevented oxidative stress, which was evidenced by a decrease in malondialdehyde and an increase in glutathione, catalase, superoxide dismutase levels. In conclusion, our data suggest that telmisartan prevented STZ-induced metabolic abnormalities and cardiovascular complications in type 2 diabetes.

Chronic treatment with an orally active angiotensin‐(1‐7) formulation decreases arterial pressure, cardiac hypertrophy and improves cardiac function in spontaneously hypertensive rats

Considering that ANG‐(1‐7) counterbalances angiotensin II hypertensive and hypertrophic effects, we aimed to assess whether chronic treatment with ANG‐(1‐7) modifies arterial blood pressure (BP), cardiac hypertrophy (CH), and cardiac function in spontaneously hypertensive rats (SHR). Male SHR (15 weeks) were treated with tap water (n=9) or oral administration of an ANG‐(1‐7)‐cyclodextrin inclusion compound (corresponding to 30mg/Kg/day Ang‐(1‐7), n=8) by gavage (10 weeks). BP (mmHg) was assessed by intraarterial catheterization, and the left ventricle (LV) pressures through carotid catheterization. CH index (CHI) was estimated by heart/body weight ratio. Data are presented as mean±SD. ANG‐(1‐7) reduced diastolic (147±5 vs 162±7), systolic (222±7 vs 202±7), and mean arterial pressures (191±6 vs 178±7). The end‐diastolic (17±5 vs 10±2) and the systolic (247±35 vs 216±34) LV pressures were decreased after treatment. Chronic ANG‐(1‐7) also slightly decreased CHI (4.12±0.10 vs 3.90±0.15) in SHR. These results indicate that chronic ANG‐1‐7) treatment decreased BP and improved cardiac function in SHR with established hypertension. The data reinforce the potential pharmacological use of ANG‐(1‐7) in managing cardiovascular diseases. Supported by: INCT‐Nanobiofar, CNPq, CAPES.

Investigation Into the Cardiac Effects of Spironolactone in the Experimental Model of Type 1 Diabetes

We have studied the effect of 8-week treatment with spironolactone (20 mg*kg(-1)*day(-1)) on cardiovascular complications associated with streptozotocin (STZ)-diabetic rats. Wistar rats were made diabetic with STZ (45 mg/kg, intravenously). Various biochemical and cardiac parameters were measured at the end of 8 weeks. STZ produced hyperglycemia; hypoinsulinemia; hyperlipidemia; increased blood pressure; increased creatinine, cardiac enzyme, and C-reactive protein levels; reduction in heart rate; and cardiac hypertrophy. Chronic treatment with spironolactone significantly prevented STZ-induced bradycardia, hypertension, and elevated fasting glucose level with simultaneous increase in serum insulin levels. It significantly reduced the elevated cholesterol, very-low-density lipoprotein, and triglyceride levels and increased the lower high-density lipoprotein-cholesterol levels in diabetic rats. Furthermore, spironolactone also produced a significant reduction in the elevated creatinine levels, C-reactive protein, and levels of lactate dehydrogenase and creatinine kinase. It also produced beneficial effect in diabetic rats by preventing cardiac hypertrophy as evident from decrease in left ventricular collagen levels, cardiac hypertrophy index, and left ventricular hypertrophy index. Our data suggest that spironolactone prevents not only the STZ-induced metabolic abnormalities but also cardiovascular complications.

Cardiovascular changes in spontaneously hypertensive rats are improved by chronic treatment with zofenopril

The aim of this study was to investigate the effect of chronic treatment with antihypertensive and non-antihypertensive doses of zofenopril on cardiovascular changes in spontaneously hypertensive rats (SHR). Male SHR were treated with 0.5 or 10 mg kg(-1) per day of zofenopril (Z(0.5) and Z(10)) for 3 months. SHR and Wistar-Kyoto rats (WKY) receiving vehicle were used as controls. Systolic blood pressure was measured using the tail cuff method. Left ventricular weight/body weight ratio was calculated as cardiac hypertrophy index. Angiotensin converting enzyme (ACE) activity was determined in plasma and tissues by a fluorimetric method. Vascular reactivity was evaluated on aortic rings by acetylcholine and sodium nitroprusside relaxations. Effects on vascular structure were assessed by lumen diameter, wall thickness and medial cross-sectional area determination. Superoxide anion generation was quantified using lucigenin-amplified chemiluminescence in aorta. Long-term daily administration of zofenopril (10 mg kg(-1)) to SHR reduced blood pressure to WKY values, decreased cardiac hypertrophy, improved the acetylcholine-induced relaxant response and reversed the vascular remodelling. ACE inhibition and antioxidant activity were involved in these effects. 0.5 mg kg(-1) per day of zofenopril slightly modified blood pressure and the other effects were weaker. Antihypertensive effects of chronic treatment with zofenopril were accompanied by recovery of endothelial function and improvement of cardiovascular structure. Low-dose zofenopril had little effect on blood pressure, with some benefits on cardiovascular structure and function. Inhibition of ACE and antioxidant activity were involved in these effects.

Modulation of impact of high fat diet in pathological and physiological left ventricular cardiac hypertrophy by fluvastatin

The male wistar rats were kept at high fat diet for 90 days and subjected to partial abdominal aortic constriction (PAAC) at 62nd and continued up to 90th day. Similarly, rats were kept at high fat diet for 90 days and subjected to chronic swimming training (CST) at 46th day and continued up to 90th day. Obesity was assessed by %age change in body weight, WHR ratio and adiposity index whereas cardiac hypertrophy was assessed by using index of cardiac hypertrophy, i.e., left ventricular weight, left ventricular weight to body weight, (LVW/BW), left ventricular wall thickness (LVWT), cardiomyocyte diameter, LV, protein content and collagen content. Further, mean arterial blood pressure (MABP) was also recorded. Oxidative stress was assessed by measuring the levels of thiobarbituric acid reactive species (TBARS), levels of superoxide anion generation and levels of reduced glutahione in left ventricular tissue. The PAAC and CST increased the index of cardiac hypertrophy. Moreover, PAAC has significantly increased MABP. Fluvastatin, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, significantly attenuated PAAC induced left ventricular cardiac hypertrophy and MABP whereas no significant change was observed in CST-induced cardiac hypertrophy. Furthermore, fluvastatin significantly attenuated the oxidative stress by decreasing the levels of TBARS and superoxide anion generation and increasing the levels of reduced glutathione. These results suggest that fluvastatin prevented the PAAC-induced cardiac hypertrophy.

Effect of telmisartan on cardiovascular complications associated with streptozotocin diabetic rats

Angiotensin receptor blockers provide cardiovascular protection in heart failure patients. We have studied the effect of 8 weeks treatment with telmisartan (5 mg kg(-1) day(-1)) on cardiovascular complications associated with streptozotocin (STZ) diabetic rats. Wistar rats were made diabetic with STZ (45 mg kg(-1), iv). Various biochemical and cardiac parameters were measured at the end of 8 weeks. STZ produced hyperglycemia, hypoinsulinemia, hyperlipidemia, increased blood pressure, increased creatinine, cardiac enzyme and C-reactive protein (CRP) levels, reduction in heart rate and cardiac hypertrophy. Chronic treatment with telmisartan significantly (P < 0.05) prevented STZ induced hypertension and elevated fasting glucose level with simultaneous increase in serum insulin levels. It significantly (P < 0.05) reduced the elevated cholesterol, very low density lipoprotein (VLDL) and triglyceride levels in diabetic rats and increased the lower high density lipoprotein (HDL)-cholesterol levels. Further, telmisartan produced a significant (P < 0.05) reduction in the elevated creatinine levels, CRP and levels of other cardiac enzyme markers like Lactate de-hydrogenase and creatinine kinase of diabetic rats. STZ-induced bradycardia was also prevented by telmisartan treatment and it also produced beneficial effect by preventing cardiac hypertrophy as evident from left ventricular collagen levels, cardiac hypertrophy index and left ventricular hypertrophy index of diabetic rats. Our data suggest that telmisartan prevents not only the STZ-induced metabolic abnormalities, but also cardiovascular complications.

Neostigmine and pilocarpine attenuated tumour necrosis factor α expression and cardiac hypertrophy in the heart with pressure overload

The inflammatory cytokine tumour necrosis factor alpha (TNF alpha) is known to be a major factor contributing to cardiac remodelling and dysfunction. Parasympathetic nervous system cholinergic function can inhibit TNF alpha expression during systemic infection. In the present study, we tested the effects of a cholinesterase inhibitor, neostigmine, and a muscarinic cholinergic agonist, pilocarpine, on cardiac hypertrophy and TNF alpha levels during pressure overload. Rats with transverse aortic constriction exhibited elevated TNF alpha protein levels in the heart, increased heart weight to body weight ratios (an index of cardiac hypertrophy) and decreased left ventricular diastolic function. Two weeks of infusion with neostigmine (6 microg kg(-1) day(-1)) or pilocarpine (0.3 mg kg(-1) day(-1)) significantly reduced cardiac hypertrophy, reduced TNF alpha levels and elevated interleukin-10 levels in heart tissues, and improved ventricular function in rats with transverse aortic constriction. Neither of these treatments significantly changed ventricular pressure load. Furthermore, in primary cultured neonatal cardiac cells, treatment with pilocarpine attenuated adrenergic agonist phenylephrine-induced increased TNF alpha expression and [3H]leucine (a marker of protein synthesis) incorporation in the cells. Collectively, both cholinergic agents decreased TNF alpha levels and attenuated cardiac hypertrophy. Since both agents potentially enhanced cholinergic function, the anti-inflammatory action may be involved in the cardioprotective effect of the treatments with these agents.

P38 Mitogen-Activated Protein Kinase Inhibition Ameliorates Angiotensin II–Induced Target Organ Damage

We investigated whether or not p38 mitogen-activated protein kinase inhibition ameliorates angiotensin II-induced target organ damage. We used double transgenic rats harboring both human renin and angiotensinogen genes (dTGRs). dTGR, with or without p38 inhibitor (BIRB796; 30 mg/kg per day in the diet), and nontransgenic Sprague-Dawley rats were studied in 2 protocols. In protocol 1 (week 7), systolic blood pressure of untreated dTGRs was 204+/-4 mm Hg, but partially reduced after BIRB796 treatment (166+/-7 mm Hg), whereas Sprague-Dawley rats were normotensive. The cardiac hypertrophy index was unchanged in untreated and BIRB796-treated dTGRs. The beta-myosin heavy chain expression of BIRB796-treated hearts was significantly lower in BIRB796 compared with dTGRs, indicating a delayed switch to the fetal isoform. BIRB796 treatment significantly reduced cardiac fibrosis, connective tissue growth factor, tumor necrosis factor-alpha, interleukin-6, and macrophage infiltration. Albuminuria was not reduced in BIRB796-treated dTGRs. Tubular and glomerular damage with tumor necrosis factor-alpha expression was unaltered, although serum creatinine and cystatin C were normalized. Renal macrophage infiltration, fibrosis, and vessel damage were reduced. In protocol 2 (week 8), we focused on mortality and arrhythmogenic electrical remodeling. Mortality of untreated dTGRs was 100% but was reduced to 10% in the BIRB796 group. Cardiac magnetic field mapping showed prolongation of depolarization and repolarization in untreated dTGRs compared with Sprague-Dawley rats with a partial reduction by BIRB796. Programmed electrical stimulation elicited ventricular tachycardias in 81% of untreated dTGRs but only in 48% of BIRB796-treated dTGRs. In conclusion, BIRB796 improved survival, target organ damage, and arrhythmogenic potential in angiotensin II-induced target organ damage.

Aortic-banding induces myocardial oxidative stress and changes in concentration and activity of antioxidants in male Wistar rats

Myocardial activity and gene expression of antioxidant defenses and oxidative damage were examined in an experimental model of pressure overload hypertrophy. Male Wistar rats were divided into abdominal aortic-banded or sham-operated groups. After 30 days, arterial pressure and heart rate were measured. Heart, lung, and liver were extracted and weighted to evaluate cardiac hypertrophy and pulmonary and hepatic congestion. Heart homogenates were prepared to quantify lipid peroxidation (LPO); the activities of superoxide dismutase (SOD), catalase (CAT), glutathione- S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GR); and Cu–Zn SOD and GST concentrations. Total glutathione (GSH) myocardial content was also measured. Arterial pressure (142 ± 17 mmHg) and cardiac hypertrophy index (3.4 ± 0.45 mg/g) were significantly increased (by 38% and 22%, respectively, p < 0.0001) in the aortic-banded group. LPO was enhanced by 55% in the aortic-banded group (11891 ± 766 cps/mg protein, p < 0.001) compared with that in the controls. SOD activity and concentration were higher (40% and 38%, 15.15 ± 1.03 U/mg protein, 49.187 pixels, respectively, p < 0.05) in the aortic-banded group than in the controls. Aortic-banding induced a decrease by 28% in GST (48 ± 10 pmol/min/mg protein, p < 0.005), by 36% in GPx (38.2 ± 9.5 nmol/min/mg protein, p < 0.005), by 31% in GR activities (1.55 ± 0.23 nmol/mg protein, p < 0.0005), and by 43% in GSH content (0.13 ± 0.02 nmol/mg protein, p < 0.005). In conclusion, in this model it was observed that myocardial oxidative stress induces alterations in antioxidant enzyme activities and protein expression. The follow up of these parameters could afford an early therapeutical window to avoid heart failure progression.

Anaerobic training and nandrolone treatment induce cardiac hypertrophy and increase left ventricle collagen content

The isolated and interactive effects of anaerobic physical training and nandrolone (N) treatment on cardiac hypertrophy and collagen content were evaluated. Male Wistar rats were randomized into 4 groups: sedentary vehicle (SV), trained vehicle (TV), sedentary nandrolone (SN) and trained nandrolone (TN − 5mg/Kg, 2x week, im). Trained rats performed jumps into water (4 sets, 10 repetitions, 50–70% body wt-load, 5 days/week, 6 weeks). Two days after the last session, the animals were sacrificed, the heart was excided, weighted and prepared to histological analysis for quantification of collagen content. The microscopic analysis consisted of measuring the fluorescent areas taken by collagen infiltration. Data were compared by bifatorial ANOVA and Tukey test (p<0.05). TN rats presented higher heart weight / body weight ratio (cardiac hypertrophy index) than the other groups (TN:2.85± 0.06 >TV:2.66± 0.04> SN:2.54± 0.05 = SV:2.47± 0.04 mg/g, p<0.05). Moreover, TN rats presented increase on cardiac collagen content compared to the other groups (TN:20.69±2.6 > SV:8.4±1.07 = SN:5.01±1.04 = TV:6.45±1.02 um2, p<0.05). These findings suggest that the association between physical training and nandrolone treatment induce cardiac hypertrophy and deleterious alterations on cardiac muscle structure. Whether the potentially detrimental influence of these factors occurs in humans and/or contributes toward sudden death in young athletes has yet to be determined. Financial Support: FAPESP, FAEP - UNICAMP, CNPq.