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

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.
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PMID:Effects of genetic hypertension on diabetic nephropathy in the rat--functional and structural characteristics. 322 Oct 96

Streptozotocin diabetes in rats was complicated by spontaneous hypertension (SHR) and myocardial infarction (MIC), considered as "risk groups". Renal function was assessed on the basis of blood urea nitrogen (BUN) and albuminuria. BUN increased by 36% in Wistar diabetic group, by 100% in SHR + diabetes, and by 51% in MIR + diabetes. Morphologic changes were assessed by estimation of PAS-positive glycosaminoglycans and measurement of vascular wall thickness of glomerular arterioles. The risk groups showed exaggerated tendency for development of diabetic angiopathy. A significant imbalance between TXA2 and prostacyclin was found, which was reflected by TXB2/6-keto-PGF1 alpha (the stable metabolites of TXA2 and prostacyclin, respectively) ratio, which increased by 38% in Wistar diabetic rats, by 61% in SHR + diabetes, and by 133% in MIR + diabetes. These changes correlated very well with increased platelet aggregability (r = 0.70; p less than 0.05) and with increased lipid peroxide level (r = 0.60; p less than 0.05), but neither with total plasma cholesterol (r = 0.20), nor with plasma triglycerides (r = 0.34). Lipid peroxides increased 5-fold in Wistar diabetic rats, 6-fold in SHR + diabetes, and 5.5-fold in MIR + diabetes. A causative relationship between TXA2/PGI2 imbalance and lipid peroxide changes on one hand, and diabetic angiopathy, on the other, was suggested.
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PMID:Streptozotocin-induced diabetes in rat. I. Influence of hypertension and myocardial infarction on the development of vascular complications. 322 39

Recent clinical reports have suggested that hypertension accelerates the progress of diabetic nephropathy and retinopathy, whereas antihypertensive treatments may retard them. Thus, the effect of antihypertensive treatment in diabetes mellitus with hypertension was evaluated in rats. A model of diabetes mellitus with hypertension has been developed in spontaneously hypertensive (SHR) rats by unilateral nephrectomy and streptozotocin (STZ, 30 mg/kg, i.v. treatment). The rats were treated with four antihypertensive drugs orally for 12 weeks thereafter. STZ treatment induced chronic hypeglycaemia (300-400 mg/dl), decreased body weight and heart rate, and caused vascular changes of ophthalmic fundi and cataracta. The kidney of these rats showed proliferative changes such as periarteritis nodosa, hyperplasia, or fibronecrosis of the arterioles, exudative changes, mesangial proliferation, or thickening of the basement membrane of the glomeruli. Enalapril (10 mg/kg per day) and remipril (Hoe 498) (1 mg/kg per day), converting enzyme inhibitors, or arotinolol (20 mg/kg per day), a beta-adrenoceptor blocking drug, decreased blood pressure, prevented the development of renal and ocular lesions, and tended to increase creatinine clearance. Nisoldipine (3 mg/kg per day), a calcium-entry blocking drug, tended to decrease blood glucose, and prevented the decrease of body weight and development of ocular lesions. In conclusion, antihypertensive treatments were effective in preventing the progress of diabetic retinopathy and nephropathy, and renal insufficiency in this animal model.
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PMID:Antihypertensive treatment in spontaneously hypertensive rats with streptozotocin-induced diabetes mellitus. 329 54

An inbred strain of stroke-prone spontaneously hypertensive rat, the M-SHRSP, was established by brother-sister breeding of selected SHRSP for 24 generations while administering apresoline. Compared with SHRSP, the M-SHRSP shows an earlier rise in blood pressure, plasma renin activity (PRA) and cerebrospinal fluid (CSF) pressure, and somewhat changed cerebrovascular lesions. Crosses and back-crosses, using M-SHRSP, Wistar-Kyoto rats (WKY), spontaneously hypercholesterolaemic (SHC) rats and their hybrids produced colonies with various blood pressure levels and hypercholesterolaemia. Continued successive selective brother-sister breeding of M-SHRSP and SHC hybrids produced a colony with severe hypertension and marked hypercholesterolaemia. Streptozotocin diabetes was induced in an M-SHRSP and SHC hybrid (TC), from which diabetic TC was successively bred to the fifth generation. While each generation was hypertensive and showed a decrease in islet B-cells, symptoms of lasting glycosuria were first observed in the fourth generation among those given a high alpha-corn starch (75.7%) diet.
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PMID:Establishment and use of the M strain of stroke-prone spontaneously hypertensive rat. 346 99

The relationship between the renin-angiotensin system (RAS) and prostacyclin (PGI2) biosynthesis was studied in experimental diabetic rats. The group with diabetes induced by streptozotocin (STZ, 3.3 mmol/kg i.v.) showed prolonged hypertension, and plasma renin activity decreased markedly from 8.4 +/- 0.7 to 2.4 +/- 0.3 and 1.2 +/- 0.3 ng angiotensin I/ml per h at 2 and 8 weeks after STZ treatment. Plasma PGI2, determined as 6-keto-PGF1 alpha, decreased significantly at 8 weeks, with the values for the STZ-treated and control groups being 1490 +/- 99 and 2210 +/- 90 pg/ml, respectively. Significant suppression of renin release from renal cortical slices was observed at 8 weeks in the diabetic group, although no significant change was found in the renal renin content when compared with that of the controls. The release of PGI2 from the renal medullary slices of the diabetic group was suppressed at 2 and 8 weeks, with the suppression in aorta and renal cortical slices being apparent only at 8 weeks. These results indicate that suppression of the RAS may be related to PGI2 biosynthesis in diabetes mellitus.
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PMID:Renin-angiotensin system and prostacyclin biosynthesis in streptozotocin diabetic rats. 636 Jun 95

Previous data showed that diabetes induced by streptozotocin for 5 days causes changes in arterial pressure control and baroreflex regulation of heart rate in male Wistar rats. The impairment of baroreflex may be related to autonomic neuropathy as described by several investigators. The aim of this study was to identify autonomic changes in short-term experimental diabetes in rats (induced for 5 days with streptozotocin 65 mg IP). Intra-arterial blood pressure signals were obtained from 6 control group and 7 diabetic group rats and processed in a data acquisition system (CODAS, 1 kHz). Both vagal and sympathetic function were assessed through intravenous injections of methylatropine and propranolol. Streptozotocin induced hyperglycemia (18.9 +/- 1.8 versus 5.8 +/- 0.2 mmol/L) and reductions in mean arterial pressure (102 +/- 2 versus 117 +/- 3 mm Hg) and resting heart rate (298 +/- 14 versus 332 +/- 2 beats per minute). Sodium and potassium levels were not different between groups. The intrinsic heart rate was reduced in the diabetic group (302 +/- 10 versus 398 +/- 6 beats per minute). This group also exhibited depressed vagal and sympathetic tone (50% and 22%, respectively), reduction of vagal effect (42%), and no change in sympathetic effect. In conclusion, early autonomic dysfunction in short-term streptozotocin-induced diabetes seems to be related to changes in arterial pressure and baroreflex control.
Hypertension 1995 Dec
PMID:Autonomic dysfunction in short-term experimental diabetes. 749 76

We have previously reported that chronic hypertension develops consistently in Wistar rats with a 25% reduction in renal mass (RRM) following the induction of insulin dependent diabetes mellitus (IDDM) with streptozotocin (STZ, 65 mg/kg body weight, intravenously). In this study, we examined the role of the endogenous digitalis-like substance in the development of hypertension. Four groups of rats were studied: 1) 25% RRM rats with STZ-induced IDDM (25-DM), 2) normal rats with STZ-induced IDDM (2K-DM), 3) 25% RRM rats with vehicle treatment (25-V), and 4) normal rats with vehicle treatment (2K-V). In 25-DM rats, blood pressure progressively increased during the 3 weeks after STZ treatment and was associated with microalbuminuria, low plasma renin activity, and extracellular volume expansion. In contrast, the 2K-DM, 25-V, and 2K-V rats remained normotensive. Furthermore, the plasma and urine levels of digoxin-like immunoreactive factor (DIF), determined by digoxin radioimmunoassay (Baxter), were significantly higher in hypertensive 25-DM rats than in their controls. The same was the case for plasma digitalis-like substance (DLS), determined by exposing canine Na+,K(+)-ATPase to plasma fractions and observing the percent inhibition. Increased DIF and DLS in hypertensive 25-DM rats was associated with a significant decrease in Na+,K(+)-ATPase activity of microsomes prepared from the left and right ventricles, when compared with microsomes from normotensive 2K-DM animals. Microsomal 5'-nucleotidase, a plasma membrane marker, was unchanged. The DIF and DLS correlated significantly with each other and with myocardial Na+,K(+)-ATPase activity and mean blood pressure. These results suggest that increased endogenous digitalis-like substance, which inhibits cardiovascular muscle cell Na(+)-K(+)-pump activity, may be involved in the mechanism of hypertension associated with IDDM in 25% RRM rats.
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PMID:Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes in reduced renal mass rats. 839 Feb 68

Myocardial beta-adrenoceptors and inotropic responses to beta-adrenoceptor agonists were studied in isolated hearts obtained from diabetic and/or hypertensive rats. Streptozotocin diabetic Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), as well as normoglycaemic SHR-stroke prone rats were used. At the age of 18-20 weeks, beta-adrenoceptor density was assessed in the left ventricle and isolated hearts were perfused according to Langendorff. Concentration response curves were made for dobutamine, salbutamol and the adenylyl cyclase activator forskolin. In both SHR and SHR-SP preparations a blunted inotropic response to beta-adrenoceptor stimulation was observed, although responses to forskolin and beta-adrenoceptor density and affinity were not different from those in normotensive hearts. In hearts taken from diabetic WKY and SHR, a decrease in beta-adrenoceptor density was observed, but no parallel blunted response to beta-adrenoceptor stimulation occurred. Moreover, the absolute (and percentual) inotropic responses to dobutamine and forskolin were increased in hearts from diabetic SHR when compared to their hypertensive normoglycaemic controls. These results suggest an impaired activity of the stimulatory G-protein in hearts obtained from hypertensive rats, whereas the simultaneous occurrence of hypertension and diabetes may result in a compensatory increase in activity of the adenylyl cyclase activated pathway.
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PMID:Beta-andrenoceptors in the hearts of diabetic-hypertensive rats: radioligand binding and functional experiments. 911 26

Epidemiological studies have established that diabetes mellitus and hypertension are independent risk factors for atherosclerosis. One of the earliest abnormalities seen in atherogenesis is enhanced monocyte adherence to the endothelium. The mechanisms by which diabetes mellitus or hypertension enhances monocyte-endothelial cell interactions are incompletely characterized. It is not known whether there are additive interactions between these risk factors on endothelial adhesiveness for monocytes. Male Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats were fed a normal or fructose-enriched diet. In some cases, animals were injected with streptozotocin (35 mg/kg body weight) to induce diabetes. After 2 weeks, plasma was drawn for biochemical measurements, and thoracic aortas were harvested, opened longitudinally, and exposed to fluorescently labeled mouse monocytoid cells (WEHI 78/24, 2 x 10(6)/mL) for 30 minutes on a rocking platform. Adherent cells were counted by epifluorescence microscopy. WEHI 78/24 binding to aortic segments from SHR animals was elevated compared with segments from WKYs. Fructose feeding alone had no effect on endothelial adhesiveness. When WKYs were made hyperglycemic by STZ injection, monocyte binding was 160% of the control value. Elevated monocyte binding was also observed in aortas derived from SHR animals injected with STZ, indicating an additive effect of hypertension and hyperglycemia. To determine whether alterations in oxidative state played a role in the endothelial adhesiveness, aortic segments were exposed to lucigenin (250 micromol/L) for measurement of superoxide anion. Aortic segments from SHR elaborated 120% more superoxide anion than did controls. Elevated free-radical production was also observed in aortas from diabetic WKYs. Furthermore, thoracic aortas derived from diabetic SHR animals elaborated more superoxide anion than did any of the other groups (374%, P<0.05). Immunohistochemical staining for monocyte chemotactic protein-1 demonstrated increased expression in aortas isolated from diabetic WKY and SHR compared with control vessels. These studies demonstrate that both diabetes and hypertension lead to increased monocyte adherence to the endothelium. This abnormality is associated with increased vascular superoxide production and monocyte chemotactic protein-1 expression. Furthermore, there appears to be an additive interaction between hyperglycemia and hypertension in their effects on endothelial adhesiveness and its determinants.
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PMID:Interaction of diabetes and hypertension on determinants of endothelial adhesiveness. 963 36

Vascular injury and impaired vascular function are central to the increased mortality associated with diabetes. Hyperglycemia in diabetes has been suggested to play a role in this process, in part by impairing the function of the vascular endothelium. It has been difficult, however, to isolate the direct effect of glucose in both humans and in animal models of diabetes. This was evaluated in the present study in 7 rats that were chronically instrumented with a Transonic flow probe at the iliac bifurcation of the abdominal aorta, a nonoccluding catheter inserted immediately anterior to the flow probe, and a femoral vein catheter. Acute infusions of acetylcholine and sodium nitroprusside (1 and 10 microg/min IA) increased hindquarter blood flow significantly by approximately 27 and 10 mL/min over baseline, respectively, at the high dose. Streptozotocin (70 mg/kg IV) was administered, but normoglycemia was maintained with continuous intravenous insulin infusion to control for potential streptozotocin side effects. Diabetes was induced 5 to 7 days later by stopping the insulin infusion. Hindlimb blood flow (measured 24 hours per day) decreased during the diabetic period and was accompanied by an increase in mean arterial pressure, suggesting a vasoconstrictor response. However, the responses to acetylcholine and sodium nitroprusside were not altered significantly on either day 2 or day 6 of the diabetic period. This suggests that neither endothelium-mediated vasorelaxation nor responsiveness to nitric oxide is impaired during the initial phase of diabetes and that diabetic hyperglycemia does not have a significant, direct effect to impair endothelium-mediated relaxation in insulin-dependent diabetes mellitus. The mechanism for the change in baseline blood flow and its potential influence on endothelial function, however, are not known.
Hypertension 1998 Sep
PMID:Acute endothelium-mediated vasodilation is not impaired at the onset of diabetes. 974 Jun 23


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