Effect of Long-Term Treatment with Enalapril in Streptozotocin Diabetic and DOCA Hypertensive Rats

Goyal, Ramesh K.; Satia, Milan C.; Bangaru, R A; Gandhi, T.P.

doi:10.1097/00005344-199808000-00021

Cited by 21 publications

(14 citation statements)

References 19 publications

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“…The vasculature is one of the main locations of the enzyme, where activity of ACE promotes vascular responsiveness and cellular proliferation. 42,43 There is evidence of a higher activity of this enzyme in serum and some tissues such as ventricle and lung 11,12,16 in STZ-induced diabetic rats, but also a reduction of activity has been described in renal tissue. 18 The objective of this study was to study the association of somatic and nACE protein expression and enzymatic activity in the renal tissue homogenate of Wistar rats, in which DM was induced by streptozotocin.…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8] Furthermore, it has been postulated that in diabetes there is a role for the RAS in mediating many of the functional effects such as changes in intraglomerular haemodynamics 9 as well as structural changes in the diabetic kidney at both glomerular and tubulointerstitium levels. 9,10 There is strong evidence that angiotensinconverting enzyme (ACE) activity is increased in serum 5,[11][12][13][14][15] and tissues such as lung, 11,12 ventricle, 16 mesenteric artery, 17 aorta and heart 18 of STZinduced diabetic rats. Insulin treatment could reverse some of these changes, 19 but the mechanism by which insulin treatment affects ACE activity is still unknown.…”

Section: Introductionmentioning

confidence: 99%

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Association of somatic and N-domain angiotensin-converting enzymes from Wistar rat tissue with renal dysfunction in diabetes mellitus

Ronchi

Irigoyen

Casarini

2007

J Renin Angiotensin Aldosterone Syst

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Diabetes mellitus (DM) is characterised by alterations in the intrarenal renin-angiotensin system (RAS). Insulin treatment may reverse these changes by an unknown mechanism.We aimed to verify the association between somatic ACE with 136 kDa (sACE) and N-domain ACE with 69 kDa (nACE) from Wistar (W) rat tissue with DM.Three groups were studied: control (CT), insulin treated diabetic (DT) and untreated (D). ACE activity was determined using Hippuryl-His-Leu and Z-Phe-His-Leu as substrates. In D group, urine ACE activity increased for both substrates when compared with CT and DT, despite the decreased activity of renal tissues. Immunostaining of renal tissue demonstrated that ACE is more strongly expressed in the proximaltubule of D than in the same nephron portion in the other groups.Angiotensin (Ang) 1-7 and Ang II are less expressed in DT group when compared with CT and D. Ang II levels decreased in the D and DT groups showed when compared to the control. Ang 1-7 was detected in all studied groups with low levels in DT.The modulation of angiotensin peptides suggests that sACE, nACE,ACE 2 and NEP could have important functions in renal RAS regulation through a counter-regulatory mechanism to protect the kidney in diabetes mellitus.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of somatic and N-domain angiotensin-converting enzymes from Wistar rat tissue with renal dysfunction in diabetes mellitus

Ronchi

Irigoyen

Casarini

2007

J Renin Angiotensin Aldosterone Syst

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“…Under STZ-induced diabetic conditions, myocardial ACE levels have been found to be unchanged and/or increased, depending on the experimental design (8,9). These inconsistent results may be the consequences of uncontrolled intracellular protein activation of the used homogenates.…”

Section: Discussionmentioning

confidence: 99%

Cardiac kinin level in experimental diabetes mellitus: role of kininases

Koch

Wendorf²,

Dendorfer³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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Diabetes mellitus impairs the cardiac kallikrein-kinin system by reducing cardiac kallikrein (KLK) and kininogen levels, a mechanism that may contribute to the deleterious outcome of cardiac ischemia in this disease. We studied left ventricular (LV) function and bradykinin (BK) coronary outflow in buffer-perfused, isolated working hearts (n ϭ 7) of controls and streptozotocin (STZ)-induced diabetic rats before and after global ischemia. With the use of selective kininase inhibitors, the activities of angiotensin I-converting enzyme, aminopeptidase P, and neutral endopeptidase were determined by analyzing the degradation kinetics of exogenously administered BK during sequential coronary passages. Basal LV function and coronary flow were impaired in STZ-induced diabetic rats. Neither basal nor postischemic coronary BK outflow differed between control and diabetic hearts. Reperfusion after 15 min of ischemia induced a peak in coronary BK outflow that was of the same extent and duration in both groups. In diabetic hearts, total cardiac kininase activity was reduced by 41.4% with an unchanged relative kininase contribution compared with controls. In conclusion, despite reduced cardiac KLK synthesis, STZ-induced diabetic hearts are able to maintain kinin liberation under basal and ischemic conditions because of a primary impairment or a secondary downregulation of kinindegrading enzymes.bradykinin; kininase; myocardial ischemia AN INCREASE IN CARDIAC KININS might be a mechanism for protecting the heart during hypertension, cardiac failure, or acute myocardial infarction (MI). Several authors have reported increased endogenous levels of kallikrein (KLK), kininogen, and bradykinin (BK) and an upregulation of B 1 and B 2 receptors in response to cardiac ischemia (1,12,15,18,25,34,35). Direct application of BK in perfusion medium improves cardiac left ventricular (LV) function, coronary flow, and myocardial metabolism and reduces the infarct size of isolated working rat hearts during and after induction of myocardial ischemia via activation of the prostaglandin and nitric oxide (NO) axis (36). Likewise, the inhibition of kinin breakdown by kininase inhibitors has been shown to exert cardioprotective effects in in vivo models of MI (11,42).Several changes of the cardiac kallikrein-kinin system (KKS) have been found under diabetic conditions that may contribute to the profoundly altered myocardial and vascular integrity during the development of diabetic cardiopathy (30,31,38). Reduced effectiveness of exogenously applied BK on vascular dilation has been reported in diabetic subjects with endothelial dysfunction (14, 39). Moreover, we and others (30, 31, 38) have described reduced endogenous cardiac kininogen and KLK levels and/or alterations in the activation of cardiac tissue KLK in diabetic animals. Thus a reduction in the BK precursor content and in the activity of the BK-forming enzyme KLK may indicate a decreased capacity for generating cardiac BK and may be among the mechanisms involved in the development of coronary...

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“…Control rats treated with PE were not studied because it has been previously shown that ACEi does not modify EC or skeletal muscle mitochondrial function under basal conditions (Bahi et al 2004). Similarly, although data are controversial concerning the blood pressure, it has been reported that ACE inhibitors do not modify blood glucose or insulin in normal rats (Predel et al 1994;Dal Ponte et al 1998;Goyal et al 1998).…”

Section: Animals and Experimental Designmentioning

confidence: 99%

Effect of angiotensin‐converting enzyme inhibition on skeletal muscle oxidative function and exercise capacity in streptozotocin‐induced diabetic rats

Rouyer¹,

Zoll²,

Daussin³

et al. 2007

Experimental Physiology

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Since exercise capacity is related to the mitochondrial respiration rate in skeletal muscle and both parameters are potentially modulated by the onset of diabetes and by inhibition of the angiotensin-converting enzyme (ACE), we investigated whether skeletal muscle oxidative functions and exercise capacities are impaired in chronic streptozotocin-induced diabetic (STZ) rats and whether ACE inhibition could reverse such abnormalities. The ACE inhibitor perindopril (2 mg kg −1 day −1 ) was given for a period of 5 weeks to 7-month-old STZ rats (DIA-PE, n = 8) whose haemodynamic function, skeletal muscle mitochondrial function and exercise capacity were compared with those of untreated diabetic (DIA, n = 8) and control rats (CONT, n = 8). Increased arterial blood pressure (157 ± 12 versus 130 ± 6 mmHg, P < 0.05) and reduced exercise capacity (29 ± 2 versus 91 ± 2 min, respectively, P < 0.01) were observed in DIA compared with CONT. The oxidative capacity of the gastrocnemius muscle was significantly reduced in DIA compared with CONT rats (5.4 ± 0.5 versus 10.6 ± 0.7 µmol O 2 min −1 (g dry weight)−1 , respectively, P < 0.001). Moreover, the coupling between oxidation and phosphorylation was significantly impaired in DIA (−52%, P < 0.001). Angiotensin-converting enzyme inhibition (ACEi) normalized blood pressure without improving mitochondrial function (4.3 ± 0.8 µmol O 2 min −1 (g dry weight) −1 in DIA-PE rats) but reduced exercise capacity to even lower levels (10 ± 1 min, P < 0.01). Exercise capacity correlated positively with blood pressure in DIA-PE (r = 0.79, P < 0.05). In experimental type 1 diabetic rats, both skeletal muscle mitochondrial respiration and exercise capacity are impaired. The ACEi failed to restore the muscular function and worsened exercise capacity. Further studies will be useful to determine whether an inadequate muscular blood flow secondary to the reduction in mean systemic blood pressure can explain these results.

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Effect of Long-Term Treatment with Enalapril in Streptozotocin Diabetic and DOCA Hypertensive Rats

Cited by 21 publications

References 19 publications

Association of somatic and N-domain angiotensin-converting enzymes from Wistar rat tissue with renal dysfunction in diabetes mellitus

Association of somatic and N-domain angiotensin-converting enzymes from Wistar rat tissue with renal dysfunction in diabetes mellitus

Cardiac kinin level in experimental diabetes mellitus: role of kininases

Effect of angiotensin‐converting enzyme inhibition on skeletal muscle oxidative function and exercise capacity in streptozotocin‐induced diabetic rats

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