A comparison of the hypotensive and hypoglycaemic actions of an angiotensin converting enzyme inhibitor, an AT1a antagonist and troglitazone

Chen, Sufang; Noguchi, Yuichi; Izumida, Taro; Tatebe, Junko; Katayama, Shigehiro

doi:10.1097/00004872-199611000-00011

Cited by 40 publications

(11 citation statements)

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“…For example, hemodynamic effects of TRO related to its reported activity to lower blood pressure in animal models and in humans could also impact pathophysiological processes in high-fat-and high-fructosefed LDLR Ϫ/Ϫ mice. [27][28][29][30] All major cell types contributing to this vascular lesion formation express PPAR␥, which provides a mechanism for the direct effect of thiazolidinedione ligands in the vessel wall. 3,5,6,9 Data from in vitro experiments had suggested mechanisms by which activation of PPAR␥ could either accelerate or attenuate the atherosclerotic process.…”

Section: Collins Et Al Troglitazone Inhibits Early Atherosclerosismentioning

confidence: 99%

Troglitazone Inhibits Formation of Early Atherosclerotic Lesions in Diabetic and Nondiabetic Low Density Lipoprotein Receptor–Deficient Mice

Collins¹,

Meehan²,

Kintscher³

et al. 2001

ATVB

359

237

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Abstract-Peroxisome proliferator-activated receptor-␥ (PPAR␥) is a ligand-activated nuclear receptor expressed in all of the major cell types found in atherosclerotic lesions: monocytes/macrophages, endothelial cells, and smooth muscle cells. In vitro, PPAR␥ ligands inhibit cell proliferation and migration, 2 processes critical for vascular lesion formation. In contrast to these putative antiatherogenic activities, PPAR␥ has been shown in vitro to upregulate the CD36 scavenger receptor, which could promote foam cell formation. Thus, it is unclear what impact PPAR␥ activation will have on the development and progression of atherosclerosis. This issue is important because thiazolidinediones, which are ligands for PPAR␥, have recently been approved for the treatment of type 2 diabetes, a state of accelerated atherosclerosis. We report herein that the PPAR␥ ligand, troglitazone, inhibited lesion formation in male low density lipoprotein receptor-deficient mice fed either a high-fat diet, which also induces type 2 diabetes, or a high-fructose diet.Troglitazone decreased the accumulation of macrophages in intimal xanthomas, consistent with our in vitro observation that troglitazone and another thiazolidinedione, rosiglitazone, inhibited monocyte chemoattractant protein-1-directed transendothelial migration of monocytes. Although troglitazone had some beneficial effects on metabolic risk factors (in particular, a reduction of insulin levels in the diabetic model), none of the systemic cardiovascular risk factors was consistently improved in either model. These observations suggest that the inhibition of early atherosclerotic lesion formation by troglitazone may result, at least in part, from direct effects of PPAR␥ activation in the artery wall.

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Section: Collins Et Al Troglitazone Inhibits Early Atherosclerosismentioning

confidence: 99%

Troglitazone Inhibits Formation of Early Atherosclerotic Lesions in Diabetic and Nondiabetic Low Density Lipoprotein Receptor–Deficient Mice

Collins¹,

Meehan²,

Kintscher³

et al. 2001

ATVB

359

237

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“…It remains to be clarified whether or not these risk factors significantly contribute to the glomerular injury of OLETF rats. Furthermore, ACE inhibitors have been reported to improve insulin resistance (17). Therefore, in the present work, to elucidate whether the renoprotective effects of ACE inhibition in OLETF rats are mainly due to a direct action or to the improvement of the above-mentioned risk factors, we compared the effects of an ACE inhibitor with the effects of amlodipine and insulin.…”

Section: Discussionmentioning

confidence: 97%

Role of Intrarenal Angiotensin-Converting Enzyme in Nephropathy of Type II Diabetic Rats

et al. 2002

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To examine the mechanism of nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a recently developed type II diabetic model, we compared the long-term effect of angiotensin-converting enzyme (ACE) inhibitor (imidapril, 1 mg/kg/day), calcium channel blocker (amlodipine, 10 mg/kg/day), and insulin (5 -10 U/kg/day) on nephropathy of OLETF rats. Both imidapril and amlodipine, but not insulin, significantly reduced blood pressure of OLETF rats. Imidapril treatment significantly decreased urinary albumin excretions and improved glomerulosclerosis of OLETF rats, while amlodipine failed to improve nephropathy of OLETF rats despite lowering of blood pressure. Insulin treatment, which significantly decreased HbA1c throughout the treatment period, did not ameliorate nephropathy of OLETF rats. Serum ACE activity in OLETF rats was significantly lower than that in genetic control nondiabetic Long-Evans Tokushima Otsuka (LETO) rats.However, glomerular and aortic ACE activities in OLETF rats were significantly higher than those in LETO rats, and were significantly decreased by treatment with imidapril. Furthermore, immunohistochemical analysis of ACE in the kidney using specific antibodies indicated greater ACE immunostaining in the glomeruli and renal vessels of OLETF rats than in those of LETO rats. These observations demonstrate that ACE is involved in the development of nephropathy of OLETF rats and provide evidence that intrarenal ACE rather than circulating ACE may play an important role in nephropathy of this type II diabetic model. sulin-dependent diabetes mellitus (IDDM). However, the effect of ACE inhibitors on the nephropathy of patients with NIDDM remains unclear, and detailed studies on nephropathy of NIDDM have been hampered by the scarcity of suitable animal models for human NIDDM.Otsuka Long-Evans Tokushima Fatty (OLETF) rats are a recently developed model of human NIDDM (8-10). OLETF rats are characterized by insulin resistance, late onset of hyperglycemia (after about 20 weeks of age), a mild and chronic course of NIDDM and subsequent conversion to IDDM, mild hypertension, and mild obesity. Very interestingly, OLETF rats exhibit pathological features of glomerulosclerosis similar to the pathological features of glomeru-

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“…As far as troglitazone, the first TZD in clinical use, is concerned, during the last decade several studies have been published indicating a BP lowering effect in animal models of the insulin resistance syndrome. In particular, troglitazone has been found to reduce BP or to protect against dietary-induced BP increase in obese Zucker rats [64,65], fructose-fed Wistar rats [66], Watanabe heritable hyperlipidemic rabbits [67], Otsuka Long-Evans Tokushima fatty rats [68,69], rats receiving a high-fat diet [70], heminephrectomized Wistar fatty rats [71], fructose-fed Sprague-Dawley rats [72], in the remnant kidney model of spontaneously hypertensive rats (SHR) [73], and in fructosefed borderline hypertensive rats [74].…”

Section: Studies With Troglitazonementioning

confidence: 99%

“…Data from animal studies on troglitazone and BP show a reduction in fasting insulin levels and/or the area under the curve for insulin under various procedures of glucose loading or prevention of the diet-induced insulin increase [65][66][67][68]70,71,74] and similar effects was shown in animal studies with ciglitazone [63], pioglitazone [87,89,[91][92][93]95] and rosiglitazone [104,108]. Accordingly, in the mentioned above human studies, apart from the improvement in the indexes of insulin sensitivity, troglitazone was associated with significant reductions in fasting plasma insulin [76][77][78]80] or C-peptide levels [45,78], whereas in the study by Ogihara et al [77] plasma insulin decrease was strongly correlated with BP reduction.…”

Section: Studies Revealing Possible Mechanisms Of Tzd-associated Bp Amentioning

confidence: 99%

PPARγ Agonists: Beneficial Effect on Blood Pressure Beyond Glycemic Control?

Sarafidis¹,

Lasaridis

2006

CHYR

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The Metabolic or Insulin Resistance Syndrome is a cluster of cardiovascular risk factors, such as type 2 diabetes mellitus, hypertension, central obesity, dyslipidaemia, and other disorders, which have been proposed to be secondary to insulin resistance. A number of possible mechanisms linking insulin resistance and compensatory hyperinsulinemia with hypertension have been described, such as renal sodium reabsorption enhancement, sympathetic nervous system activation, or blunted insulin-mediated vasodilatation due to endothelial dysfunction. PPAR agonists or thiazolidine-diones (TZDs) are a class of oral antihyperglycemic agents that act through improvement of insulin sensitivity. Apart from their action on glycemic control, in several studies TZDs have been also reported to exert beneficial effects on other parameters of the metabolic syndrome. This review summarizes the literature data on the effect of troglitazone, pioglitazone and rosiglitazone on blood pressure (BP), which derive from animal and human studies that were either specifically designed to determine the effect of TZDs on BP or just examined BP levels among other parameters. In addition, it presents in vitro and in vivo evidence about various TZDs actions on the cardiovascular system that could positively influence BP, representing therefore possible mechanisms of this BP amelioration.

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A comparison of the hypotensive and hypoglycaemic actions of an angiotensin converting enzyme inhibitor, an AT1a antagonist and troglitazone

Cited by 40 publications

References 0 publications

Troglitazone Inhibits Formation of Early Atherosclerotic Lesions in Diabetic and Nondiabetic Low Density Lipoprotein Receptor–Deficient Mice

Troglitazone Inhibits Formation of Early Atherosclerotic Lesions in Diabetic and Nondiabetic Low Density Lipoprotein Receptor–Deficient Mice

Role of Intrarenal Angiotensin-Converting Enzyme in Nephropathy of Type II Diabetic Rats

PPARγ Agonists: Beneficial Effect on Blood Pressure Beyond Glycemic Control?

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A comparison of the hypotensive and hypoglycaemic actions of an angiotensin converting enzyme inhibitor, an AT1a antagonist and troglitazone

Cited by 40 publications

References 0 publications

Troglitazone Inhibits Formation of Early Atherosclerotic Lesions in Diabetic and Nondiabetic Low Density Lipoprotein Receptor–Deficient Mice

Troglitazone Inhibits Formation of Early Atherosclerotic Lesions in Diabetic and Nondiabetic Low Density Lipoprotein Receptor–Deficient Mice

Role of Intrarenal Angiotensin-Converting Enzyme in Nephropathy of Type II Diabetic Rats

PPAR&#947; Agonists: Beneficial Effect on Blood Pressure Beyond Glycemic Control?

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PPARγ Agonists: Beneficial Effect on Blood Pressure Beyond Glycemic Control?