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1.
Aims/hypothesis: To investigate the interaction between hypertension and diabetic nephropathy, we studied the renal accumulation of fibronectin
in a genetic model of hypertension with streptozotocin-induced diabetes mellitus.
Methods: Spontaneously hypertensive rats (SHR) and their genetically normotensive control Wistar Kyoto rats (WKY) were studied at
4 weeks of age. The rats were killed 20 days after the induction of diabetes mellitus. The renal accumulation of fibronectin
was estimated using Western blot analysis as well as immunofluorescence technique and confocal microscopy.
Results: Blood glucose concentrations were similar in diabetic SHR rats (27 ± 3.3 mmol/l) and WKY rats (25.5 ± 2.7 mmol/l). The systolic
blood pressure was higher in both groups of SHR rats than in the control rats. The abundance of renal fibronectin as detected
by Western blot analysis was (p < 0.05) higher in the diabetic SHR rats (41.4 ± 15.0 densitometric U, n = 8) than in the control rats, and no difference was observed between diabetic and control WKY rats (20.8 ± 6.2, n = 8) and (27.8 ± 17.2, n = 8). The mean peak intensity of fibronectin signal within the glomerulus as estimated by confocal microscopy was higher
(p < 0.05) in the diabetic SHR rats (32.9 ± 3.5) than in control SHR rats (11.9 ± 5.7) or diabetic (7.4 ± 2.2) and control (15.2
± 7.9) WKY rats.
Conclusion/interpretation: In experimental diabetes the presence of genetic hypertension promotes earlier accumulation of renal fibronectin, a matrix
protein implicated in renal glomerulosclerosis. [Diabetologia (2001) 44: 2088–2091]
Received: 11 January 2001 and in revised form: 30 May 2001 相似文献
2.
Effects of genetic hypertension on diabetic nephropathy in the rat--functional and structural characteristics 总被引:3,自引:0,他引:3
M E Cooper T J Allen R C O'Brien P A Macmillan B Clarke G Jerums A E Doyle 《Journal of hypertension》1988,6(12):1009-1016
Streptozotocin (STZ) diabetes was induced in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Body weight, blood pressure, renal function, glycaemic control and proteinuria were assessed monthly for 32 weeks. At 32 weeks, the animals were killed and glomerular basement membrane (GBM) thickness and fractional mesangial volume were measured. There was no significant difference in renal function between diabetic SHR and diabetic WKY. Diabetic SHR showed an earlier and larger rise in total proteinuria and urinary albumin excretion than diabetic WKY. Urinary albumin excretion was increased more than tenfold in diabetic SHR compared to diabetic WKY after 32 weeks of diabetes. GBM thickness was significantly increased in diabetic SHR compared with diabetic WKY. Both diabetic WKY and diabetic SHR showed mesangial expansion when compared to their nondiabetic counterparts. On the other hand, both hypertensive models showed increased glomerular volume, which was not influenced by the presence of diabetes. The diabetic SHR model has features of accelerated nephropathy, as evidenced by increased albuminuria and GBM thickness. This suggests that pre-existing hypertension may play an important role in the progression of diabetic renal disease. 相似文献
3.
M E Cooper T J Allen P Macmillan L Bach G Jerums A E Doyle 《American journal of hypertension》1988,1(1):5-10
To evaluate whether hypertension is a cause or just an association with diabetic renal disease, diabetes was induced in both normotensive Wistar-Kyoto and spontaneously hypertensive rats (WKY and SHR). Animals were assessed monthly for 8 months before sacrifice. When compared to normotensive diabetic rats (WKY-STZ), hypertensive diabetic rats (SHR-STZ) had an earlier and more rapid rise in urinary albumin excretion. In addition, SHR-STZ had increased glomerular basement membrane thickness when compared to WKY-STZ or SHR. In a separate experiment, Enalapril therapy (35 mg/L) was administered in drinking water to WKY-STZ and SHR-STZ. Enalapril significantly reduced blood pressure in both animal groups, and this was associated with a decrease in urinary albumin excretion. The SHR-STZ model has accelerated nephropathy as determined by both functional and structural parameters. Angiotensin-converting enzyme inhibition is associated with a reduction in albuminuria in both hypertensive and normotensive models of diabetic nephropathy. 相似文献
4.
Aminoguanidine inhibits the development of accelerated diabetic retinopathy in the spontaneous hypertensive rat 总被引:4,自引:0,他引:4
Dr. H. -P. Hammes M. Brownlee D. Edelstein M. Saleck S. Martin K. Federlin 《Diabetologia》1994,37(1):32-35
Summary Arterial hypertension has been identified as a major secondary risk factor for diabetic retinopathy. However, the mechanisms by which hypertension worsens retinopathy are unknown. Inhibition of advanced glycation product formation prevents the development of experimental diabetic retinopathy in normotensive diabetic rats. In this study the effect of hypertension on the rate of diabetic retinopathy development and the formation of arteriolar thrombosis was evaluated. We also evaluated the effect of aminoguanidine, an inhibitor of advanced glycation end product formation on retinal pathology of diabetic hypertensive rats. After 26 weeks of diabetes, hypertension accelerated the development of retinopathy despite a lower mean blood glucose level than in the non-hypertensive group (diabetic spontaneous hypertensive rats (SHR) 16.00±6.83 mmol/l; diabetic normotensive Wistar Kyoto rats (WKY) 34.9±3.64 mmol/l; p<0.0001). Diabetic SHR had nearly twice as many acellular capillaries as diabetic WKY (SHR diabetic: 91.9±7.5 acellular capillaries per mm2 of retinal area vs WKY diabetic: 53.7±8.5 acellular capillaries per mm2 of retinal area), and a 3.8-fold increase in the number of arteriolar microthromboses (SHR diabetic 23504±5523 m2 vs SHR non-diabetic 6228±2707 m2). Aminoguanidine treatment of SHR diabetic rats reduced the number of acellular capillaries by 50%, and completely prevented both arteriolar deposition of PAS-positive material and abnormal microthrombus formation. These data suggest that hypertension-induced deposition of glycated proteins in the retinal vasculature plays a central role in the acceleration of diabetic retinopathy by hypertension. 相似文献
5.
Duration of obesity is a risk factor for non-insulin-dependent diabetes mellitus, not for arterial hypertension or for hyperlipidaemia 总被引:2,自引:0,他引:2
Obesity is often accompanied by non-insulin-dependent diabetes mellitus (type 2), arterial hypertension, and hyperlipidaemia.
The aim of this study was to evaluate whether duration of obesity is a risk factor for the appearance of type 2 diabetes,
hypertension, and hyperlipidaemia. We studied 760 obese subjects, 207 of whom had normal glucose tolerance, 125 impaired glucose
tolerance, and 428 type 2 diabetes; in addition, 560 had hypertension and 315 had hyperlipidaemia. At univariate analysis,
passing from normal through impaired glucose tolerance to type 2 diabetes there was a progressive increase of age and of duration
of obesity, hypertension and hyperlipidaemia. Compared to subjects without hypertension, hypertensive subjects were older,
had a longer duration of obesity, a greater body mass index (BMI, kg/m2), and more frequently a family history of hypertension; they also more frequently showed impaired glucose tolerance and type
2 diabetes and hyperlipidaemia. Compared to subjects without hyperlipidaemia, hyperlipidaemic subjects were older, had a longer
duration of obesity, and more frequently showed impaired glucose tolerance and type 2 diabetes, and hypertension. Diabetes,
hypertension, and hyperlipidaemia were highly associated, as up to 80% of subjects with type 2 diabetes had hypertension,
and more than 80% of hyperlipidaemic subjects had hypertension. Type 2 diabetes was less frequent than hypertension and hyperlipidaemia
during the first 10 years of obesity, and progressively increased thereafter; in contrast the frequency of hypertension and
of hyperlipidaemia increased only after 30 years of obesity. In 359 subjects undergoing an oral glucose tolerance test (168
with simultaneous determination of insulin release), increasing durations of obesity were accompanied by an increasing prevalence
of type 2 diabetes, and in deterioration of glucose response, with no decrease in insulin release. At logistic regression
analysis, age was a common risk factor for diabetes, hypertension, and hyperlipidaemia; duration of obesity and hyperlipidaemia
were additional risk factors for diabetes; family history of hypertension, BMI and hyperlipidaemia were additional risk factors
for hypertension, as were impaired glucose tolerance or diabetes, and hypertension for hyperlipidaemia. These data indicate
that duration of obesity is a risk factor for type 2 diabetes, and emphasize the importance of preventing obesity in young
subjects.
Received: 31 July 1997 / Accepted in revised form: 18 May 1998 相似文献
6.
Hypertensive diabetic animal models have been developed by injecting streptozotocin (STZ) in neonatal stroke-resistant spontaneously hypertensive rats (SHRSR) and stroke-prone SHR (SHRSP) at the age of two days. After the treatment, the animals showed mild insulin deficiency and mild hyperglycemia at the age of three to four months. Diabetic nephropathy was produced particularly in STZ-treated SHRSR at the age of six months. The effect of neonatal STZ injection on hyperglycemia varied among normotensive Wistar-Kyoto rats (WKY), SHRSR, and SHRSP; SHRSR showed the highest glucose levels, SHRSP showed intermediate levels, and WKY was the lowest. All STZ-treated SHRSR showed glycosuria, while glycosuria was not observed in the treated SHRSP and WKY. Histologic study indicated that these strain differences were partly ascribed to differences in islet B-cell sensitivity to toxic effects of STZ. The development of hypertension was not accelerated in these SHRSR and SHRSP compared with respective nontreated controls. Since STZ-treated SHRSR develop mild diabetic symptom with hypertension and develop mild diabetic glomerulosclerosis, they are good models for studying vascular complications or other problems relating to the synergism between hypertension and diabetes mellitus. 相似文献
7.
Diabetic glomerulopathy in the SHR/N-corpulent rat: role of dietary carbohydrate in a model of NIDDM
Dr. M. T. Velasquez A. A. Abraham P. L. Kimmel T. Farkas-Szallasi O. E. Michaelis IV 《Diabetologia》1995,38(1):31-38
Summary We evaluated the course of diabetes and nephropathy in the SHR/N-cp (corpulent) rat characterized by genetic obesity, non-insulin-dependent
diabetes (NIDDM), and hypertension, and examined whether the nephropathy in this model is influenced by the type of carbohydrate
intake. Two groups of obese and lean SHR/N-cp rats were fed diets containing 54 % carbohydrate, as either sucrose or starch
for 3 months (group I) and 9 months (group II). After 3 months on either diet, group I obese rats had higher 2-h response
serum glucose levels and urinary glucose excretion than lean rats. Sucrose feeding was associated with greater proteinuria
and a higher percentage of abnormal glomeruli in obese rats. Morphometric evaluation of glomeruli (by computerized image analysis)
showed greater mean renal corpuscular volume and mesangial fraction in obese than in lean rats fed similar diets. Mean renal
corpuscular volume and mesangial fraction were also greater in sucrose-fed obese rats than in starch-fed obese rats. After
9 months, group II obese rats had substantial reductions in serum and urine glucose levels but they were still hyperinsulinaemic
and showed more proteinuria than lean rats and a higher percentage of sclerotic glomeruli compared with group I obese rats.
At this time, mean mesangial fraction but not renal corpuscular volume was still higher in obese than in lean rats. In group
I obese rats, a significant correlation was found between mesangial fraction and urinary protein excretion (r = 0.67, p < 0.05). In group II obese rats, renal corpuscular volume was correlated with percentage of glomerular sclerosis (r = 0.60, p < 0.05). Thus, obese SHR/N-cp rats develop persistent proteinuria and glomerulopathy marked by glomerular enlargement, increased
mesangial matrix, and progressive glomerular sclerosis. Sucrose feeding accentuates mesangial expansion and glomerulosclerosis
in obese rats. [Diabetologia (1995) 38: 31–38]
Received: 14 February 1994 and in revised form: 5 July 1994 相似文献
8.
Tomassoni D Bellagamba G Postacchini D Venarucci D Amenta F 《Clinical and experimental hypertension (New York, N.Y. : 1993)》2004,26(4):305-321
The influence of hypertension associated with diabetes on cerebrovascular and frontal cortex or hippocampus microanatomy was investigated in 20-week-old spontaneously hypertensive rats (SHR) in which diabetes was induced by treatment with streptozotocin (STZ) and in control or STZ-diabetic age-matched normotensive Wistar Kyoto (WKY) rats. At the beginning of experiment, systolic pressure values were similar in WKY rats either control, or exposed to STZ and remarkably higher in control or STZ-treated SHR. Systolic pressure values increased in the different animal groups examined along the course of experiment. Blood glucose levels were increased in either STZ-WKY rats or -SHR compared to WKY rats and SHR respectively. The main changes occurring in pial and intracerebral arteries of SHR and STZ-SHR were thickening of the arterial wall accompanied by luminal narrowing. In medium sized pial arteries of STZ-WKY rats luminal narrowing and a decreased thickness of arterial wall were noticeable. Intracerebral arteries of STZ-WKY diabetic rats showed a not homogeneous sensitivity of different sized branches. The volume of zones III and IV of frontal cortex was decreased in SHR and STZ-SHR compared to control WKY rats. The number of nerve cells in these cerebrocortical layers was decreased to a similar extent in SHR. STZ-WKY rats or STZ-SHR compared to control WKY rats. In dentate gyrus, followed by the CA1 subfield of hippocampus, decreased volume and number of neurons were found in SHR and STZ-SHR compared to control WKY rats. The occurrence of astrogliosis was observed in hypertensive, diabetic or hypertensive plus diabetic rats. The above findings indicate the occurrence of cerebrovascular and brain microanatomical changes in SHR and to a lesser extent in STZ-diabetic rats compared to control normotensive and normoglicemic WKY rats. Association of hypertension and diabetes caused more pronounced changes than in the single disease models. These results support the view that hypertension and diabetes affect the structure of cerebrovascular tree and of brain and that association of the two diseases results in an increased risk of target-organ damage, involving brain. 相似文献
9.
Md Abdul Hye Khan Lauren Kolb Melissa Skibba Markus Hartmann René Blöcher Ewgenij Proschak John D. Imig 《Diabetologia》2018,61(10):2235-2246
Aims/hypothesis
The metabolic syndrome is a cluster of risk correlates that can progress to type 2 diabetes. The present study aims to evaluate a novel molecule with a dual action against the metabolic syndrome and type 2 diabetes.Methods
We developed and tested a novel dual modulator, RB394, which acts as a soluble epoxide hydrolase (sEH) inhibitor and a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist in rat models of the metabolic syndrome—the obese spontaneously hypertensive (SHROB) rat and the obese diabetic Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat. In SHROB rats we studied the ability of RB394 to prevent metabolic syndrome phenotypes, while in ZSF1 obese diabetic rats we compared RB394 with the ACE inhibitor enalapril in the treatment of type 2 diabetes and associated comorbid conditions. RB394 (10 mg/kg daily) and enalapril (10 mg/kg daily) were administered orally for 8 weeks.Results
RB394 blunted the development of hypertension, insulin resistance, hyperlipidaemia and kidney injury in SHROB rats and reduced fasting blood glucose and HbA1c, improved glucose tolerance, reduced blood pressure and improved lipid profiles in obese ZSF1 rats. A reduction in liver fibrosis and hepatosteatosis was evident in RB394-treated obese ZSF1 rats. Unlike RB394, enalapril did not demonstrate any positive effects in relation to diabetes, hyperlipidaemia or liver dysfunction in obese ZSF1 rats. RB394 ameliorated diabetic nephropathy by reducing renal interstitial fibrosis and renal tubular and glomerular injury in obese diabetic ZSF1 rats. Intriguingly, enalapril demonstrated a weaker action against diabetic nephropathy in obese ZSF1 rats.Conclusions/interpretation
These findings demonstrate that a novel sHE inhibitor/PPAR-γ agonist molecule targets multiple risk factors of the metabolic syndrome and is a glucose-lowering agent with a strong ability to treat diabetic complications.10.
《Clinical and experimental hypertension (New York, N.Y. : 1993)》2013,35(6):1003-1019
Streptozotocin (STZ)-induced diabetes depresses the rate of vascular collagen synthesis in the spontaneously hypertensive rat (SHR), but it also reduces arterial pressure (SAP) in this strain. We investigated this phenomenon further by comparing the SHR with the renovascular hypertensive (RVH) rat, because diabetes does not affect SAP in the latter model of hypertension. Renovascular hypertension was induced by clipping the left renal artery of Wistar-Kyoto (WKY) rats; sham-operated WKY were included as normotensive controls. Collagen synthesis of arterial tissue in vitro was quantified as prolyl hydroxylase activity and the rate of radioactive proline incorporation into collagen. Arterial collagen synthesis of nondiabetic SHR and RVH animals was elevated compared to that of the nonhypertensive WKY controls. STZ-induced diabetes (8 weeks) reduced SAP of SHR, but had no effect on SAP of either RVH or normotensive WKY rats. However, diabetes significantly depressed vascular collagen synthesis of both SHR and RVH rats, and, less consistently, of the WKY. The results strongly suggest that STZ-induced diabetes in SHR impairs arterial collagen synthesis independent of associated changes in arterial pressure. 相似文献
11.
Kazo Kaizu Qie Yue Ling Kohei Uriu Masanori Ikeda Osamu Hashimoto Norikuni Komine Sumiya Eto 《Journal of diabetes and its complications》1995,9(4):224-226
Diabetic Sprague-Dawley (SD) rats are known to exhibit renal hyperfiltration and hyperperfusion accompanied by renal hypertrophy. We examined whether such characteristics of renal hemodynamics in diabetic SD rats are also observed in diabetic spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. SHR and WKY rats were divided into four groups: D-S, diabetic SHR; N-S, nondiabetic SHR; D-W, diabetic WKY rats; and N-W, nondiabetic WKY rats. Streptozotocin (STZ), 90 mg, was intraperitoneally injected to induce diabetes. Renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by a clearance method with paraaminohypurate and insulin, respectively, 7–12 days after diabetes induction. In D-S and D-W, there was no increase in the kidney weight and RBF, in spite of significant increases in GFR and fasting blood sugar levels. These results indicate that, in both WKY and SHR, diabetes does not always produce renal hypertrophy and does not result in an increase in RBF. 相似文献
12.
Elham Memarian Ralph Heijmans Roderick C. Slieker Adriana Sierra Olga Gornik Joline W. J. Beulens Maja Hanic Petra Elders Julio Pascual Eric Sijbrands Gordan Lauc Viktoria Dotz Clara Barrios Leen M. ’t Hart Manfred Wuhrer Mandy van Hoek 《Diabetes/metabolism research and reviews》2023,39(7):e3685
Aims/Hypothesis
Inflammation is important in the development of type 2 diabetes complications. The N-glycosylation of IgG influences its role in inflammation. To date, the association of plasma IgG N-glycosylation with type 2 diabetes complications has not been extensively investigated. We hypothesised that N-glycosylation of IgG may be related to the development of complications of type 2 diabetes.Methods
In three independent type 2 diabetes cohorts, plasma IgG N-glycosylation was measured using ultra performance liquid chromatography (DiaGene n = 1815, GenodiabMar n = 640) and mass spectrometry (Hoorn Diabetes Care Study n = 1266). We investigated the associations of IgG N-glycosylation (fucosylation, galactosylation, sialylation and bisection) with incident and prevalent nephropathy, retinopathy and macrovascular disease using Cox- and logistic regression, followed by meta-analyses. The models were adjusted for age and sex and additionally for clinical risk factors.Results
IgG galactosylation was negatively associated with prevalent and incident nephropathy and macrovascular disease after adjustment for clinical risk factors. Sialylation was negatively associated with incident diabetic nephropathy after adjustment for clinical risk factors. For incident retinopathy, similar associations were found for galactosylation, adjusted for age and sex.Conclusions
We showed that IgG N-glycosylation, particularly galactosylation and to a lesser extent sialylation, is associated with a higher prevalence and future development of macro- and microvascular complications of diabetes. These findings indicate the predictive potential of IgG N-glycosylation in diabetes complications and should be analysed further in additional large cohorts to obtain the power to solidify these conclusions. 相似文献13.
J. A. Fagerudd K. J. Pettersson-Fernholm C. Grönhagen-Riska P.-H. Groop 《Diabetologia》1999,42(5):519-526
Aims/hypothesis. There is substantial evidence for a role of genetic factors in the development of diabetic nephropathy. In Pima Indians,
a link between susceptibility to diabetic nephropathy and Type II (non-insulin-dependent) diabetes mellitus has been proposed.
In this study, our aim was to examine the association between a family history of Type II diabetes and diabetic nephropathy
in patients with Type I (insulin-dependent) diabetes mellitus. Methods. In a cross-sectional case-control study, we assessed the prevalence of Type II diabetes in the parents of 137 Type I diabetic
patients with diabetic nephropathy (albuminuria > 300 μg/min in two of three overnight urine collections) compared with the
parents of 54 Type I diabetic patients without nephropathy (albuminuria < 20 μg/min). Results. Thirty-four (25 %) of the patients with nephropathy compared with five (9 %) of the patients without nephropathy had a parental
history of Type II diabetes (p = 0.019). A parental history of Type II diabetes was associated with a three-fold risk [odds ratio 2.95 (95 % confidence
interval: 1.03 to 8.40), p = 0.043] of diabetic nephropathy after adjustment for sex, glycaemic control and family history of hypertension. Furthermore,
there was an excess of risk factors for development of Type II diabetes (higher fasting plasma glucose concentrations, higher
prevalence of hypertension, higher waist-hip ratio and a tendency towards more glucose intolerance) among previously non-diabetic
parents of patients with nephropathy. Conclusion/interpretation. Genetic or environmental factors or both related to familial Type II diabetes increase susceptibility to diabetic nephropathy
in patients with Type I diabetes. [Diabetologia (1999) 42: 519–526]
Received: 30 September 1998 and in final revised form: 28 December 1998 相似文献
14.
15.
Simão S Gomes P Pinto V Silva E Amaral JS Igreja B Afonso J Serrão MP Pinho MJ Soares-da-Silva P 《Experimental gerontology》2011,46(6):468-474
Oxidative stress has been hypothesized to play a role in aging and age-related disorders, such as hypertension. This study compared levels of oxidative stress and renal expression of oxidant and antioxidant enzymes in male normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) at different ages (3 and 12 months). In the renal cortex of 3-month old SHR increases in hydrogen peroxide (H2O2) were accompanied by augmented expression of NADPH oxidase subunit Nox4 and decreased expression of antioxidant enzymes SOD1 and SOD3. A further increase in renal H2O2 production and urinary TBARS was observed in 12-month old WKY and SHR as compared with 3-month old rats. Similarly, expressions of NADPH oxidase subunit p22phox, SOD2 and SOD3 were markedly elevated with age in both strains. When compared with age-matched WKY, catalase expression was increased in 3-month old SHR, but unchanged in 12-month old SHR. Body weight increased with aging in both rat strains, but this increase was more pronounced in WKY. In conclusion, renal oxidative stress in 12-month old SHR is an exaggeration of the process already observed in the 3-month old SHR, whereas the occurrence of obesity in 12-month old normotensive rats may partially be responsible for the age-related increase in oxidative stress. 相似文献
16.
PETER JERNTORP 《Journal of internal medicine》1987,222(4):319-322
ABSTRACT Possible risk factors for cardiovascular disease were studied in 52 type II diabetic subjects, 19 with and 33 without a history of coronary heart disease (CHD). None of the recognized risk factors, such as hypertension, hyperlipidaemia, smoking and blood glucose imbalance, could be related to CHD. However, all female patients with CHD were lacking a family history of diabetes, while seven of nine female diabetic subjects without a history of CHD had diabetes in the family (p<0.02). This was confirmed in a second study of 150 type II diabetic subjects; CHD was more common among female patients without compared to those with diabetes in the family; 9/38 and 1/28, respectively (p<0.03). Diabetes increases the risk of CHD, and it does so for women more than it does for men. The finding of a possible low CHD risk in female diabetic subjects with diabetes in the family supports the hypothesis of genetic factors being important for the pathogenesis of cardiovascular disease in diabetes mellitus. 相似文献
17.
Renal sympathetic antidiuretic, antinatriuretic, and vasoconstrictor responses are mediated by alpha 1-adrenergic receptors in the normal rat. Since the renal nerve has been implicated in the pathogenesis of rat genetic hypertension, we investigated renal alpha 1-adrenergic receptor coupling to phosphoinositide turnover in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). In cortical slices from adult (13-week-old) SHR and WKY, stimulation with norepinephrine (10(-7)-10(-3) M) caused a concentration-dependent increase in accumulation of [3H]inositol phosphates. However, dose-response curves for SHR characteristically displayed a depression of the maximum response as compared with those for WKY. Baseline accumulation of [3H]inositol phosphates was not different between strains (39.4 +/- 2.2 cpm/mg tissue/hr for WKY and 34.4 +/- 2.1 cpm/mg tissue/hr for SHR slices; n = 5 rats/group, determined in triplicate). Antagonist competition studies revealed that norepinephrine-stimulated (10(-4) M) [3H]inositol phosphate accumulation was mediated by alpha 1-adrenergic receptors (IC50) for prazosin: 65 +/- 11 nM for SHR and 64 +/- 5 nM for WKY). The reduction in norepinephrine-stimulated [3H]inositol phosphate accumulation in SHR cortex was not the result of the hypertension, since it was also present in cortical slices from young (4-week-old) SHR in which the blood pressure was not yet significantly different from that in WKY and since [3H]inositol phosphate accumulation was unchanged from control values in rats made hypertensive by treatment with deoxycorticosterone acetate. Scatchard analysis of [3H]prazosin binding in renal cortical membranes of young and adult SHR and WKY revealed no significant differences in alpha 1-adrenergic receptor density or affinity between strains at either age. Our results suggest that renal alpha 1-adrenergic receptor coupling to phospholipase C is less efficient in SHR than in WKY. This impaired response is not the result of hypertension or changes in receptor density; this defect may play a role in increased renal sympathetic nerve activity and in the development or maintenance of hypertension in SHR. 相似文献
18.
Summary Diabetic nephropathy tends to develop more readily in patients with a family history of hypertension and/or disturbances
in sodium transport across the plasma membrane. This prompted us to study the renal effects of diabetes mellitus in a rat
strain which is predisposed to develop salt-sensitive hypertension, the Dahl salt-sensitive rat. Diabetes is associated with
several aberrations in the renal handling of sodium, such as elevation of tubular Na+, K+ATPase activity. This effect was more pronounced in Dahl salt-sensitive than in Dahl salt-resistant rats. Severe renal lesions,
characteristic of the advanced phase of diabetic nephropathy are very rarely observed in rats with streptozotocin diabetes.
However, 2 months after induction of diabetes, the Dahl salt-sensitive rats had morphological signs of advanced glomerular
disease. The urinary albumin concentration was very high, but did not correlate with the blood pressure. Non-diabetic Dahl
salt-sensitive rats as well as Dahl salt-resistant diabetic and non-diabetic rats had little or no signs of glomerular disease
and consistently very low urinary albumin concentrations. [Diabetologia (1997) 40: 367–373]
Received: 4 June 1996 and in revised form: 22 November 1996 相似文献
19.
Incidence of end-stage renal disease in Type 2 (non-insulin-dependent) diabetes mellitus in pima indians 总被引:3,自引:0,他引:3
R. G. Nelson J. M. Newman W. C. Knowler M. L. Sievers C. L. Kunzelman D. J. Pettitt C. D. Moffett S. M. Teutsch P. H. Bennett 《Diabetologia》1988,31(10):730-736
Summary The incidence of end-stage renal disease was determined in the Pima Indians of the Gila River Indian Community in Arizona, a population with a high prevalence of Type 2 (non-insulin-dependent) diabetes mellitus. Between 1975 and 1986, from a study population of 5059 subjects, end-stage renal disease occurred in 80 persons, 76 (95%) of whom had Type 2 diabetes. A review of the cases with end-stage renal disease indicated that among the diabetic subjects only two cases could be attributed to nondiabetic renal disease; all other cases were attributable to diabetic nephropathy. In diabetic Pima Indians the incidence rate of end-stage renal disease did not change during the study period, was similar in men and women, and was not effected by age at diagnosis of diabetes or by attained age, but did increase significantly with hypertension (p<0.05). The incidence of end-stage renal disease attributed to diabetic nephropathy increased from 0 cases/1000 person-years at 0–5 years to 40.8 cases/1000 person-years at 20 years duration of diabetes. In these subjects with Type 2 diabetes, the incidence rate of end-stage renal disease was similar to that in subjects with Type 1 (insulin-dependent) diabetes who were followed at the Joslin Clinic in Boston, Massachusetts when those with similar duration of diabetes were compared. 相似文献
20.
Kazuaki Shimamoto Nobuyuki Ura 《Clinical and experimental hypertension (New York, N.Y. : 1993)》2013,35(6):543-552
Insulin resistance and hyperinsulinemia are common findings in patients with essential hypertension. Recent evidence indicates that these impairments in glucose metabolism may play a role not only in the development of type 2 diabetes, but also in the onset and persistence of hypertension, dyslipidemia, and abdominal obesity. The accumulation of these risk factors constitutes a high-risk group of cardiovascular diseases, the so-called metabolic syndrome. Insulin resistance has also been reported in several animal models for hypertension, including the spontaneously hypertensive rat (SHR) and the fructose-fed rat (FFR). SHRs and FFRs have been employed in many studies to investigate the mechanisms and pathophysiology of insulin resistance and hypertension, but the precise mechanism of insulin resistance remains to be clarified. In this review, the possible mechanisms of insulin resistance in SHRs and FFRs are summarized. 相似文献