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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to investigate the link between the changes in vascular responsiveness associated with hyperinsulinemia in established STZ-induced diabetes and the growth factors signal system. We have shown that in rats with established diabetes, high-insulin treatment can enhances NA-induced contractility. This enhancement probably results from an upregulation of the expression of the mRNA for the alpha 1B- or alpha 1D-adrenergic receptor that is secondary to the hyperinsulinemia. The above effects may be made possible as a result of the increase in IGF-1 receptors and the decreased IGFBPs expressions that occur in the aorta in long-term insulin deficiency. In contrast, those insulin treatments can normalise the impaired endothelium-dependent relaxation, probably by inducing an overexpression of eNOS and VEGF. Furthermore, the expression of the IGF-1 receptor was higher in the aorta in insulin-treated diabetic than in untreated diabetes. This presumably increased the expression of VEGF mRNA, and the increased VEGF presumably upregulated eNOS, thereby resulting in an amelioration in the endothelial dysfunction otherwise seen in diabetic rats. The downside is that such a perturbation of the activity in the IGF-1 system in diabetes could be a key event in the progress of arteriosclerosis and hypertension in syndromes involving hyperinsulinemia.
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PMID:[Possible involvement of IGF-1 receptor and IGF-binding protein in insulin-induced enhancement of noradrenaline response in diabetic rat aorta]. 1472 18

Vascular disease is one of the complicating features of diabetes mellitus. Magnesium deficiency has recently been proposed as a novel factor implicated in the pathogenesis of diabetes complications. Several studies have indicated that hypertension in diabetic patients is an independent altered reaction of blood vessels to neurotransmitters and circulating hormones. Since magnesium has been proposed to decrease vascular sensitivity to vasoconstrictor agents, the present study was designed to determine whether chronic magnesium sulfate administration could prevent vascular complications of STZ-induced diabetes in rats. The animals were divided into six groups: two groups served as controls and received tap water for 8 weeks, while in the other four groups, made diabetic with a single IV injection of 40 mg/kg STZ, two groups treated with magnesium sulfate (10 g/L) added to the drinking water, and the other two groups received tap water only. After 8 weeks, in 3 groups (control, diabetic and Mg-treated), left common carotid artery was cannulated for continuous recording of blood pressure. All animals in these groups were decapitated and blood samples were drawn for glucose, Ca and Mg measurements. In the 3 remaining groups (again divided into control, diabetic and Mg-treated), the mesenteric vascular bed was perfused according to the McGregor method, and descending thoracic aortas were used for measurement of elasticity. In diabetic rats, plasma glucose was significantly increased and plasma magnesium was significantly decreased compared to controls and Mg-treated animals. Although plasma magnesium of Mg-treated animals increased significantly, it failed to reach to the magnesium level of the control group. Ca/Mg ratio was also increased compared to the control and Mg-treated animals. Mean arterial blood pressure in diabetics was significantly higher than control and Mg-treated rats. Similarly, there was a significant difference in mean arterial blood pressure of Mg-treated rats compared to control animals. Baseline perfusion pressure of diabetic group was significantly higher than control and Mg-treated groups with intact and denuded endothelium. Magnesium sulfate treatment decreased mean perfusion pressure of mesenteric vascular bed in intact and denuded endothelium in comparison with non-treated diabetic rats. There was a significant increase in passive tension in the aorta of diabetic rats compared to control and Mg-treated rats. However, there was no significant difference between Mg-treated and control rats. From the results of this study it may be concluded that magnesium could control STZ-induced diabetes and prevent its vascular complications.
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PMID:Oral magnesium administration prevents vascular complications in STZ-diabetic rats. 1568 Mar 10

This study investigated the effects of varying doses of L-NAME on arterial pressure (AP), baroreflex control, and heart rate (HR)/AP variability in the STZ-diabetic rat. Fifty-two male Wistar rats were injected with 50 mg/kg IV STZ (diabetes, D, n = 24) or citrate (controls, C, n = 28) 30 days before recordings. After 16 days, they received 14 days of oral L-NAME, 10 (H10) or 30 (H30) mg/kg, or water. Catheters were implanted into the femoral artery and vein (PE-10) for measurements in conscious rats; recorded data were analyzed on a beat-to-beat basis. Mean AP was higher in CH30 versus C and in DH10 and DH30 versus D rats. Reflex tachycardia was blunted in CH30 and DH30 rats (b = -1.81, -1.41, -0.48 in C, CH10, and CH30, respectively, P < 0.05 and b = -1.45, -1.19, -0.28 in D, DH10, and DH30, respectively, P < 0.05). Although HR and AP variability were reduced in CH30 and DH30 rats versus C and D rats, the DH30 rat had more accentuated dysfunction. All doses of L-NAME produced similar AP responses in experimental versus control groups, independent of the disease state (diabetes). Thus, autonomic dysfunction is more related to the L-NAME dose used and to the association of diabetes and hypertension than to AP values.
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PMID:Dose-dependent autonomic dysfunction in chronic L-NAME-hypertensive diabetic rats. 1622 61

The renin-angiotensin system has been implicated in the etiology of the cardiovascular complications of diabetes. Our studies extend these findings to show a specific role for angiotensin AT1a receptors in mediating diabetes-induced hypertension. Male angiotensin AT1a knockout (AT1aKO) and wild-type (AT1aWT) mice with arterial telemetric catheters were injected with streptozotocin (STZ; 150 mg/kg ip). The STZ dose was selected on the basis of a dose-response experiment in C57/BL mice. Blood glucose, water intake, body weight, blood pressure (BP), and heart rate (HR) were measured over a 2-wk period. Estimates of BP and HR variance (BPV and HRV) and their low- and high-frequency domains were also determined. STZ induced similar levels of hyperglycemia and polydypsia in the groups. Mean arterial pressure (MAP) was increased from 100 +/- 6 to 124 +/- 6 mmHg in diabetic AT1aWT. MAP was unchanged in AT1aKO (80 +/- 4 vs. 85 +/- 5 mmHg, basal vs. STZ). Treatment with an ACE inhibitor, captopril, produced a greater reduction in MAP (-18%) in diabetic AT1aWT than in AT1aKO (-3.4%). BPV was lower in AT1aKO (19 +/- 0.5 vs. 9 +/- 2 mmHg(2), AT1aWT vs. AT1aKO). Diabetes reduced BPV but only in AT1aWT (19 +/- 0.5 vs. 8 +/- 1 mmHg(2), basal vs. STZ). There were no changes in HR in either group. In AT1aKO, STZ increased HRV and its high-frequency domain with no changes seen in AT1aWT. Results document that ANG AT1a receptors are critical in diabetes-induced hypertension and in cardiac autonomic responses.
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PMID:Deficiency in angiotensin AT1a receptors prevents diabetes-induced hypertension. 1712 30

Vascular endothelial growth factor (VEGF) plays a pivotal role in diabetic retinopathy (DR) and hypertension has been identified as an independent risk factor for DR. The aim of the present study was to: (1) explore whether beta-adrenergic blockers influence retinal VEGF expression; (2) determine the effect of angiotensin-converting enzyme inhibitors (ACEI) on retinal VEGF expression independently of their anti-hypertensive actions; and (3) investigate the correlation between retinal VEGF expression and changes in retinal capillary basement membrane thickness (BMT). Streptozotocin-induced diabetic rats and control animals were assigned at random to receive the beta-adrenergic blocker propranolol, the ACEI fosenopril sodium, or vehicle for 24 weeks. Enzyme linked immunosorbent assay, immunohistochemistry, Western blot, and real-time reverse transcription-polymerase chain reaction were used to assess VEGF protein and mRNA expression. Computer-assisted morphometric measurements of transmission electron microscopy photographs were performed to evaluate BMT. Vitreous fluid and retinal VEGF protein and retinal VEGF mRNA expression were significantly higher in diabetic rats than in control rats, with a significant reduction in fosenopril sodium-treated diabetic rats (p<0.01). There was no significant difference in VEGF levels in diabetic rats and propranolol-treated diabetic rats (p>0.05), but there was a significant difference in VEGF protein and mRNA expression in propranolol-treated diabetic rats and fosenopril sodium-treated diabetic rats (p<0.01) without any significant difference in systolic blood pressure in the latter two groups (p>0.05). There was a significant correlation between the level of retinal VEGF expression and changes in retinal BMT (p<0.01). These findings suggest that the effect of ACEI on retinal VEGF expression is independent of their anti-hypertensive actions and that ACEI could offer particular benefits beyond blood pressure reduction in the treatment of DR with or without hypertension. beta-adrenergic blockers had no influence on retinal VEGF expression in normal or diabetic rats.
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PMID:Effects of angiotensin-converting enzyme inhibitors and beta-adrenergic blockers on retinal vascular endothelial growth factor expression in rat diabetic retinopathy. 1730 21

Many clinical trials have demonstrated that angiotensin converting enzyme inhibitors have protective effects on organ damage, suggesting the importance of inhibition of the renin-angiotensin system. In this study, we investigated the effects of a non-depressor dose of imidapril on organ damage induced by diabetes and hypertension. Diabetes was induced by an intravenous injection of streptozotocin (STZ, 40 mg/kg) in 15-week-old male spontaneously hypertensive rats (SHR). Imidapril (2 mg/kg/day) or vehicle was given orally for 28 days, and then the heart weight, left ventricle mass (LVM), urinary albumin excretion (UAE) and endothelial function were examined, as well as the urinary NOx level and local hepatocyte growth factor (HGF) expression. There were no significant differences between the treated groups in systolic blood pressure and plasma parameters. On the other hand, UAE was significantly suppressed in the imidapril-treated group (450+/-44 mg/day) compared to the vehicle-treated group (963+/-182 mg/day) (p<0.01). Moreover, endothelial function assessed by dilative reaction to acetylcholine as well as cardiac hypertrophy assessed by both heart/body weight ratio and LVM were significantly improved in the imidapril-treated group (p<0.05 and p<0.01, respectively). The urinary NOx concentration and local HGF expression in vessel walls were also significantly increased in the imidapril-treated group (p<0.01). A non-depressor dose of imidapril showed protective effects against organ damage in diabetic SHR, which may be partially due to the increase of HGF and NO.
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PMID:Improvement of organ damage by a non-depressor dose of imidapril in diabetic spontaneously hypertensive rats. 1733 32

Streptozotocin-induced pancreatic injury is commonly used for creating rodent models of type 1 diabetes which develop renal injury with similarities to human diabetic nephropathy. This model can be established in genetically modified rodents for investigating the role of molecular mechanisms and genetic susceptibility in the development of diabetic nephropathy. In this report, the authors describe and compare the current protocols being used to establish models of diabetic nephropathy in rat and mouse strains using streptozotocin. The authors also list some of the histological criteria and biochemical measurements which are being used to validate these models. In addition, our review explains some of the key aspects involved in these models, including the impact of streptozotocin-dosage, uninephrectomy, hypertension and genetically modified strains, which can each affect the development of disease and the interpretation of findings.
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PMID:Rodent models of streptozotocin-induced diabetic nephropathy. 1749 21

Diabetes aggravates the clinical severity and represents an additional independent risk factor of hypertension. Since both diseases separately concur to cardiomyocyte apoptosis, a mechanism at least partly involving unbalanced oxidative stress, we investigated whether the combination of diabetes and hypertension potentiated cardiac cell death in experimental models, compared to either disease alone. We also evaluated the short-term effects of different drugs in these models. Streptozotocin-induced diabetic normotensive (WKY) or hypertensive (SHR) rats were treated for one week with a DA(2)/alpha(2) agonist (CHF-1024), a selective beta1 adrenergic blocker (metoprolol), an angiotensin II-receptor blocker (valsartan) or a radical scavenger (tempol). In separate experiments, isolated cardiomyocytes were cultured in high glucose medium (25 mM) containing the same drugs. Although the number of apoptotic cardiomyocytes and the myocardial density of oxygen radicals were higher in non diabetic hypertensive than in normotensive controls, diabetes raised these variables to comparable absolute levels in both strains. All drugs except metoprolol significantly reduced apoptosis and oxidative stress in the diabetic animals of both strains and in the isolated myocytes cultured with high glucose. In conclusion, hypertensive rat is no more susceptible than its normotensive control to acute apoptosis induced by diabetes. Oxidative stress might be considered the common trigger for cardiac myocyte apoptosis in both conditions.
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PMID:Effect of beta-adrenergic and renin-angiotensin system blockade on myocyte apoptosis and oxidative stress in diabetic hypertensive rats. 1782 49

Insulin resistance is accompanied by hyperinsulinemia and activation of the renin-angiotensin system, both of which are associated with hypertension. Because the kidney plays a major role in the regulation of blood pressure, we studied the regulation of insulin receptor expression in the kidney during states of insulin resistance. Using two rat models of insulin resistance, Western blot analysis demonstrated a significant reduction in the expression of insulin receptor subunits in the kidney compared to lean control rats. Treatment of insulin resistance in Zucker rats with the insulin-sensitizing drug rosiglitazone partially restored renal insulin receptor levels. Conversely, treatment with the angiotensin II type 1 receptor (AT1) antagonist candesartan increased renal insulin receptor expression compared to untreated rats. Streptozotocin-induced hyperglycemia, which results from hypoinsulinemia, reduced expression of renal insulin receptors. Hyperinsulinemia induced by insulin infusion, however, did not produce a similar effect. In conclusion, insulin receptors are downregulated in the kidneys of insulin resistant rats, possibly mediated by hyperglycemia and angiotensin II.
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PMID:Reduced expression of insulin receptors in the kidneys of insulin-resistant rats. 1785 44

Considering the growing importance of the interaction between components of kallikrein-kinin and renin-angiotensin systems in physiological and pathological processes, particularly in diabetes mellitus, the aim of the present study was to investigate the effect of enalapril on the reduced response of bradykinin and on the interaction between angiotensin-(1-7) (Ang-(1-7)) and bradykinin (BK), important components of these systems, in an insulin-resistance model of diabetes. For the above purpose, the response of mesenteric arterioles of anesthetized neonatal streptozotocin-induced (n-STZ) diabetic and control rats was evaluated using intravital microscopy. In n-STZ diabetic rats, enalapril treatment restored the reduced response to BK but not the potentiation of BK by Ang-(1-7) present in non-diabetic rats. The restorative effect of enalapril was observed at a dose that did not correct the altered parameters induced by diabetes such as hyperglycemia, glicosuria, insulin resistance but did reduce the high blood pressure levels of n-SZT diabetic rats. There was no difference in mRNA and protein expressions of B1 and B2 kinin receptor subtypes between n-STZ diabetic and control rats. Enalapril treatment increased the B2 kinin receptor expression. From our data, we conclude that in diabetes enalapril corrects the impaired BK response probably by increasing the expression of B2 receptors. The lack of potentiation of BK by Ang-(1-7) is not corrected by this agent.
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PMID:Enalapril treatment corrects the reduced response to bradykinin in diabetes increasing the B2 protein expression. 1819 Sep 98


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