Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of microelectrode techniques for studying oxygen distribution and blood flow in the eye of a physiologically well maintained rat provides a very convenient model in which to study oxygen supply to the retina. The availability of rat models of vascular disease such as diabetes and hypertension, and the existence of several models of retinal degeneration, make studies of oxygen supply in the rat eye of particular relevance. The experiments reported in this paper demonstrate changes in oxygen distribution and blood flow very early in STZ induced diabetes. Thus, we have established a preparation in which the role of changes in oxygen supply can be correlated with the pathological events that are apparent later in the disease.
 ...
PMID:Oxygen tension and blood flow in the retina of normal and diabetic rats. 128 5

The effect of acute streptozotocin-induced diabetes mellitus on the systemic hemodynamic parameters was studied in conscious rats by thermodilution technique. Male Wistar rats were made diabetic with a single intravenous injection of streptozotocin (STZ, 50 mg/kg). The most important finding of this work was the elucidation of the systemic vasodilation and increased cardiac index one day after STZ injection. Such alteration in hemodynamic parameters could result in the increased blood flow and capillary hypertension in some vascular beds and, therefore, be considered as a pathogenic factor in the development of diabetic microangiopathy.
 ...
PMID:[Parameters of systemic hemodynamics in conscious rats with acute streptozotocin diabetes]. 142 Dec 17

Several lines of evidence suggest that hypertension is a contributing factor to diabetic nephropathy, a major cause of mortality in diabetes mellitus patients. The present study tested the hypotheses (1) that insulin dependent diabetes (IDD) causes hypertension, and (2) that simultaneous hypertension and IDD causes greater renal damage than would be expected from the independent contributions of each disease. IDD was induced by injection of streptozotocin (STZ, 65 mg/kg i.p.) into male Wistar rats, causing severe hyperglycaemia within 4 days. Seven days after the STZ treatment, hypertension was initiated by subcutaneous implantation of deoxycorticosterone acetate and administration of 1% saline in the drinking water (DOCA-NaCl). IDD rats not receiving DOCA-NaCl displayed a small elevation of blood pressure one week after STZ treatment, but thereafter displayed significant hypotension. The IDD rats receiving DOCA-NaCl displayed elevated systolic arterial pressure throughout the study, but by the end of the experiment, their mean systolic arterial pressure was significantly lower than that of the rats treated with DOCA-NaCl alone. Only the IDD/DOCA-NaCl rats displayed significant signs of renal dysfunction, i.e. greatly increased proteinuria and morphological renal damage, including marked distension of distal tubules and occasional casts. No other group displayed these abnormalities.
 ...
PMID:Effects of simultaneous diabetes and hypertension in an insulin dependent diabetic model. 176 11

The influences of hypertension and hypothyroidism on diabetic cardiomyopathy are not clear. We studied this problem further by characterizing the effects of chronic triiodothyronine (T3) treatment on cardiac performance of diabetic renovascular hypertensive (RVH) rats. Hypertension was effected by clipping the left renal artery of Wistar-Kyoto (WKY) rats, and diabetes was induced 2 weeks later by streptozotocin (STZ; 55 mg/kg i.v.). The WKY strain was selected because it is relatively resistant to the cardiodepressant effects of diabetes, so that the influence of superimposed hypertension would be more apparent. Performance of working Krebs-Henseleit buffer perfused hearts was quantified by measuring left ventricular pressure and flow characteristics. The results showed that renovascular clipping caused a marked hypertension and left ventricular hypertrophy (LVH) but had no effect on perfused heart performance after 10 weeks. They also showed that diabetes during the final 8 weeks (i) caused a marked impairment in the performance of perfused hearts ex vivo of hypertensive rats but had no measurable effect in the normotensive WKY, (ii) had no effect on arterial pressure of either the normotensive or the hypertensive rats but reduced heart rate of hypertensive animals in vivo, and (iii) caused equivalent hyperglycemia, hypoinsulinemia, and hypothyroidism (depressed serum T3 and T4 levels) of hypertensive and normotensive rats. Treatment of diabetic RVH rats with T3 (10 micrograms.kg-1.day-1) in vivo was nearly as effective as insulin therapy (10 U.kg-1.day-1) in preventing the cardiac dysfunction ex vivo and was as effective as insulin therapy in preventing the bradycardia in vivo and the decline loss.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cardiac function of the diabetic renovascular hypertensive rat: effects of insulin and thyroid hormone treatment. 205

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.
 ...
PMID:Genetic hypertension accelerates nephropathy in the streptozotocin diabetic rat. 283 66

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.
 ...
PMID:Antihypertensive treatment in spontaneously hypertensive rats with streptozotocin-induced diabetes mellitus. 329 54

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.
 ...
PMID:Renin-angiotensin system and prostacyclin biosynthesis in streptozotocin diabetic rats. 636 Jun 95

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.
 ...
PMID:Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes in reduced renal mass rats. 839 Feb 68

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.
 ...
PMID:Interaction of diabetes and hypertension on determinants of endothelial adhesiveness. 963 36

Abnormalities in cardiac function have been extensively documented in experimental and clinical diabetes. These aberrations are well known to be exaggerated when hypertension and diabetes co-exist. The objective of the present study was to examine whether alterations in the activity of the myocardial Na+-Ca2+ exchanger (NCX) can account for the deleterious effects of diabetes and (or) hypertension on the heart. To this aim, the following experimental groups were studied: (i) control; (ii) diabetic; (iii) hypertensive; and (iv) hypertensive-diabetic. Wistar rats served as the control group (C) while Wistar rats injected with streptozotocin (STZ, 55 mg/kg) served as the diabetic (D) group. Spontaneously hypertensive (SH) rats were used as the hypertensive group (H) while SH rats injected with STZ served as the hypertensive-diabetic (HD) group. Sarcolemma was isolated from the ventricles of the C, D, H, and HD groups and NCX activity was examined using rapid quenching techniques to study initial rates over a [Ca2+]o range of 10-160 microM. The Vmax of NCX was lower in the D group when compared with the C group (D, 2.96 +/- 0.26 vs. C, 4.0 +/- 0.46 nmol x mgprot(-1) x s(-1), P < 0.05), however combined diabetes and hypertension (HD) did not affect the Vmax of NCX activity (HD, 3.84 +/- 0.88 vs. H, 3.59 +/- 0.24 nmol x mgprot(-1) x s(-1), P > 0.05). However, analysis of the Km values for Ca2+ indicated that both the D and HD groups exhibited a significantly lower Km when compared with their respective control groups (D, 42 +/- 4 vs. C, 56 +/- 4 microM, P < 0.05; HD, 33 +/- 7 vs. H, 51 +/- 8 microM, P < 0.05). Immunoblotting using polyclonal antibodies (against canine cardiac NCX) exhibited the typical banding of 160, 120, and 70 kDa. The 120 kDa band is believed to represent the native exchanger with its post-translational modifications. Examination of the blots revealed a lower intensity of the 120 kDa band in the D group when compared with the C group, however, no significant difference in the HD group was observed. We speculate that the lower Vmax in the D group may be due to a reduced concentration of exchanger protein in the membrane. The absence of this defect in the HD group may be a result of compensatory mechanisms to the overall hemodynamic overload, however, this remains to be determined. The increased affinity for Ca2+ in both the D and HD groups (determined by the lower Km values) is an interesting finding and may be due to changes in sarcolemmal lipid bilayer composition secondary to diabetes-induced hyperlipidemia.
 ...
PMID:Effects of diabetes and hypertension on myocardial Na+-Ca2+ exchange. 1074 55


1 2 3 4 Next >>