Cardiovascular effects of captopril and enalapril in obese Zucker rats

Duarte, Juan; Martínez, Andrés Sánchez; Bermejo, Almudena; Vera, Beatriz; Gamez, M. J.; Cabo, P.; Zarzuelo, Antonio

doi:10.1016/s0014-2999(98)00879-6

Cited by 43 publications

(25 citation statements)

References 40 publications

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“…Captopril did not affect NOS inhibition, although it completely prevented development of hypertension and left ventricular hypertrophy in this group [16,17] . In obese Zucker rats, a model of non-insulin-dependent diabetic hypertensive rats, captopril at a dose of 50 mg/kg was effective in reversing hypertension and cardiac hypertrophy in addition to correction of insulin resistance [18] . Endothelial NOS (eNOS) knockout mice showed age-dependent morphologic and functional cardiac dysfunction represented by dilated ventricles, at systole and diastole, together with reduced ejection fraction [19] .…”

Section: Discussionmentioning

confidence: 99%

“…Inhibition of the renin-angiotensin system by ACE inhibitor captopril was shown to protect against renal damage induced by chronic hypertension, diabetes or irradiation [18,[20][21][22][23][24] . Duarte et al [18] showed that the SH-containing ACE inhibitor captopril at a high dose level of 50 mg/kg inhibited proteinuria in obese Zucker rats, a model of non-insulin-dependent diabetic hypertensive rats.…”

Section: Discussionmentioning

confidence: 99%

“…Duarte et al [18] showed that the SH-containing ACE inhibitor captopril at a high dose level of 50 mg/kg inhibited proteinuria in obese Zucker rats, a model of non-insulin-dependent diabetic hypertensive rats. In rats with and without autoimmune Heymann nephritis and treated with L -NAME, captopril partly prevented albuminurea and inhibited the L -NAME-enhanced peritubular mononuclear cell infi ltration in rats with nephritis [21] .…”

Section: Discussionmentioning

confidence: 99%

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Effects of Captopril on Cardiac and Renal Damage, and Metabolic Alterations in the Nitric Oxide-Deficient Hypertensive Rat

Khattab¹,

Mostafa²,

Al‐Shabanah³

2005

Kidney Blood Press Res

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Chronic inhibition of nitric oxide (NO) synthesis is characterized by increased blood pressure accompanied with both cardiac hypertrophy as well as renal damage. We investigated whether the angiotensin-converting enzyme (ACE) inhibitor captopril can inhibit the cardiac hypertrophy and reverse the renal failure. We tested the influence of captopril on the nitrate-nitrite (NO_x) in plasma and heart and kidney tissues. Oxidative stress, in terms of glutathione and thiobarbituric acid-reactive substances measured as malondialdehyde, was monitored examining their involvement in the cardioprotective and renoproptective actions. Three groups of Wistar rats were used: untreated group, and rats treated with the NO synthase inhibitor N_w-nitro-L-arginine methyl ester (L-NAME) and L-NAME plus captopril (10 mg/kg/day). Systolic, diastolic and mean blood pressure (BPs, BPd and BPm respectively) was measured weekly in addition to the heart rate using rat-tail plethysmography. After 3 weeks, L-NAME significantly increased BPs, BPd and BPm. Captopril treatment reversed the increments in pressure back to normal values by the fourth week. ACE inhibition by captopril reverted the L-NAME-induced hypertrophy and inhibited the enzymatic indices of cardiac damage (glutamate oxaloacetate transaminase and lactate dehydrogenase) back to normal values. Furthermore, the NO synthesis inhibition produced renal damage as indicated by significant increase in creatinine. Captopril ameliorated the raised creatinine to normal. Chronic L-NAME treatment increased serum NO_x levels but concomitant treatment with captopril was without effect.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Effects of Captopril on Cardiac and Renal Damage, and Metabolic Alterations in the Nitric Oxide-Deficient Hypertensive Rat

Khattab¹,

Mostafa²,

Al‐Shabanah³

2005

Kidney Blood Press Res

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“…The present study used telemetric recording to test the hypothesis that hyperglycemic, diabetic obese (compared with normoglycemic, nondiabetic lean) Zucker rats have elevated arterial pressure and that a high salt diet further elevates arterial pressure in obese (but not lean) Zucker rats. The present study also tested the hypotheses that the sympathetic nervous system, 17,22 the renin-angiotensin system, 7,11 and changes in vascular reactivity 8,20,21,[27][28][29][30] contribute to the elevated arterial pressure observed in Zucker rats.…”

mentioning

confidence: 84%

Elevated Sympathetic Activity Contributes to Hypertension and Salt Sensitivity in Diabetic Obese Zucker Rats

et al. 2000

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Abstract-Zucker rats are a useful model in which to define the mechanisms that link obesity to diabetes and associated cardiovascular disease. The present study tests the hypothesis that diabetic obese (compared with nondiabetic lean) Zucker rats are hypertensive and display a further increase in arterial pressure when fed a high salt diet. Male, nondiabetic lean and diabetic obese Zucker rats were chronically instrumented with telemetry probes and fed a basal salt diet for 3 weeks followed by exposure to a high salt diet for 11 days. On the basal diet, obese (vs lean) rats had significantly higher arterial pressures (Ϸ13 mm Hg), and the high salt diet significantly elevated mean arterial pressure (MAP) in obese (but not lean) Zucker rats (Ϸ12 mm Hg). Blockade of the sympathetic nervous system with hexamethonium caused a significantly larger decrease in MAP in obese (vs lean) Zucker rats fed the basal diet (51 vs 33 mm Hg), but the high salt diet did not increase the hexamethonium-induced reduction in arterial pressure in obese rats. Acute blockade of angiotensin receptors with losartan resulted in similar decreases in MAP in both groups on either diet. Acetylcholine-induced vasodilatory capacity of the carotid artery was significantly less in the obese (vs lean) Zucker rats. Together these data indicate that increased sympathetic nervous system activity and decreased vascular reactivity may contribute to elevated arterial pressure in type 2 diabetic, obese Zucker rats, but the sympathetic nervous system does not appear to contribute to the dietary salt-sensitive hypertension in this model. which results in numerous pathological changes, including nephropathy, retinopathy, neuropathy, and cardiovascular disease. Of these factors, cardiovascular disease is the single largest cause of death in diabetes mellitus, accounting for an estimated 80% of deaths in diabetic individuals. 2 The risk of cardiovascular disease in diabetic individuals is increased by concomitant hypertension, which occurs in an estimated 70% of type 2 diabetic patients. 3 Results from the Framingham 4 and MRFIT 5 trials indicate that the coexistence of the 2 diseases triples the risk of cardiovascular disease. Moreover, the presence of hypertension probably accelerates diabetic nephropathy, which in turn exacerbates the hypertension, creating a vicious feedforward cycle that contributes to the extremely high occurrence of end-stage kidney failure in type 2 diabetic patients. 6

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“…Group I received citrate buffer and normal saline and served as the control, group II received citrate buffer and enalapril treatment, group III received STZ and normal saline and served as the diabetic control, while group IV received STZ and enalapril treatment. The dose of enalapril 10 mg/kg body weight was selected based on earlier studies in which enalapril shows the protective effect in STZ-induced diabetic model (Duarte et al 1999;Baluchnejadmojarad et al 2004). Enalapril was freshly prepared in distilled water and given at the dose of 10 mg/kg orally by gavage for four and eight consecutive weeks.…”

Section: Experimental Design and Dosing Schedulementioning

confidence: 99%

Enalapril reduces germ cell toxicity in streptozotocin-induced diabetic rat: investigation on possible mechanisms

Kushwaha

Jena

2011

Naunyn-Schmiedeberg's Arch Pharmacol

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Diabetes mellitus, a state of persistent hyperglycemia, is a major cause of micro- and macrovascular diseases. It affects nearly every system in the body including the reproductive system. Abnormalities in spermatogenesis and sexual function have been documented in animal models for both types of diabetes. The purpose of the present study is to determine the possible protective effects of enalapril against the germ cell toxicity in diabetic rat. Sprague-Dawley rats were divided into four groups: (1) control, (2) control + enalapril, (3) diabetic, and (4) diabetic + enalapril. Enalapril was administered per orally for 4 and 8 weeks continuously. After the treatment, animals were sacrificed and blood glucose level, sperm count, sperm DNA damage, apoptotic cell death, immunohistochemistry of 8-oxo- 7,8-dihydro- 2'-deoxyguanosine, and the cellular toxicity were performed. Furthermore, western blotting was performed to evaluate the expression of NFκB and COX-2 in testes. The results of the present study indicate that intervention of enalapril ameliorates the sperm DNA damage, reduces the oxidative stress, and down-regulates the expression of NFκB and COX-2 expression in streptozotocin-induced diabetic rat.

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Cardiovascular effects of captopril and enalapril in obese Zucker rats

Cited by 43 publications

References 40 publications

Effects of Captopril on Cardiac and Renal Damage, and Metabolic Alterations in the Nitric Oxide-Deficient Hypertensive Rat

Effects of Captopril on Cardiac and Renal Damage, and Metabolic Alterations in the Nitric Oxide-Deficient Hypertensive Rat

Elevated Sympathetic Activity Contributes to Hypertension and Salt Sensitivity in Diabetic Obese Zucker Rats

Enalapril reduces germ cell toxicity in streptozotocin-induced diabetic rat: investigation on possible mechanisms

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