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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Streptozotocin (STZ) treatment on neonatal rats produces a non-insulin-dependent diabetes mellitus (NIDDM) model in adulthood. Applying this model to spontaneously hypertensive rats (SHR), we designed the present study to develop a new model of NIDDM with genetic hypertension. Two-day-old male and female SHR were intraperitoneally injected with 25.0-75.0mg/kg STZ, and two-day-old Wistar Kyoto rats (WKY) of both sexes, which are a normotensive control strain for SHR, were similarly injected with 75.0-150.0mg/kg STZ. Control rats received vehicle alone. The relationships between the doses of the STZ injected and the changes of the metabolic variable and blood pressure were examined for 12 weeks following the treatment. Plasma glucose levels in male SHR increased in a dose-dependent manner at 12 weeks, control 122 +/- 8 (SEM) mg/dl, 25.0mg/kg STZ 139 +/- 13mg/dl (ns), 37.5mg/kg STZ 240 +/- 51mg/dl (ns), 50.0mg/kg STZ 359 +/- 39mg/dl (p less than 0.01), 62.5mg/kg STZ 419 +/- 33mg/dl (p less than 0.001) and 75.0mg/kg STZ 513 +/- 10mg/dl (p less than 0.001), whereas in male WKY, only mild hyperglycemia developed in case of the higher doses of STZ given, control 112 +/- 4mg/dl, 75.0mg/kg STZ 136 +/- 18mg/dl (ns), 100.0mg/kg STZ 204 +/- 40mg/dl (ns), 125.0mg/kg STZ 219 +/- 37mg/dl (p less than 0.05), and 150.0mg/kg STZ 177 +/- 12mg/dl (p less than 0.01). The development of hypertension was not affected by the neonatal STZ treatment in male SHR at 11 weeks, systolic blood pressure being control 210 +/- 7mmHg, 25.0mg/kg STZ 217 +/- 5mmHg (ns), 37.5mg/kg STZ 202 +/- 3mmHg (ns), 50.0mg/kg STZ 216 +/- 6mmHg (ns), 62.5mg/kg STZ 210 +/- 6mmHg (ns), and 75.0mg/kg STZ 209 +/- 5mmHg (ns). For the long-term observation, STZ-treated male SHR were divided into mild diabetes group (plasma glucose at 12 weeks less than 300mg/dl, mean 195 +/- 21mg/dl) and severe diabetes group (greater than or equal to 300mg/dl, mean 445 +/- 18mg/dl). Hyperglycemia in both groups was maintained until 28 weeks, plasma glucose being control 112 +/- 4mg/dl, mild diabetes group 161 +/- 10mg/dl (p less than 0.01), and severe diabetes group 419 +/- 25mg/dl (p less than 0.001) but it later gradually ameliorated, plasma glucose at 52 weeks being control 120 +/- 3mg/dl, mild diabetes group 131 +/- 7mg/dl (ns), and severe diabetes group 220 +/- 43mg/dl (ns). However, hypertension persisted in both diabetes groups until 52 weeks, systolic blood pressure being control 209 +/- 6mmHg, mild diabetes group 199 +/- 9mmHg (ns), and severe diabetes group 221 +/- 6mmHg (ns).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A new animal model of non-insulin-dependent diabetes mellitus with hypertension: neonatal streptozotocin treatment in spontaneously hypertensive rats. 183 97

The sodium-proton exchange activity was determined in lymphocytes of spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), and domestic Wistar rats. Uptake of sodium was determined by measuring the osmotic swelling of lymphocytes after activation of the exchanger by suspension of the cells in sodium propionate and consequent intracellular acidification by the permeant weak acid. Fractional swelling (mean +/- SEM) in 16 SHR and 16 WKY was 0.44 +/- 0.03 and 0.35 +/- 0.02, respectively (p less than 0.01). The swelling was partially inhibitable by amiloride and, at 10(-4) M concentration, the amiloride-sensitive swelling was 0.21 +/- 0.02 in SHR and 0.11 +/- 0.01 in WKY (p = 0.001). Progressive extracellular ion substitutions of chloride for propionate or of potassium for sodium showed that the exchange activity was related linearly to cellular acidification; however, the dependence on extracellular sodium displayed saturation characteristics, with the same apparent Km for cells from SHR and WKY and a Vmax of 0.54 +/- 0.03 for SHR and 0.39 +/- 0.02 for WKY (p less than 0.002). External lithium could replace sodium on the exchanger but abolished the differences between strains. Results in the domestic Wistar rats were similar to those of WKY. These results suggest that lymphocytes of the SHR have a greater capacity for sodium uptake through the sodium-proton exchanger, as compared with normotensive strains. If shared by other cells, such an increased capacity could have a pathophysiological role in genetic hypertension. In particular, its presence in proximal renal tubular cells would support the hypothesis of a primary role for the kidney in the pathogenesis of genetic hypertension.
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PMID:Lymphocyte membrane sodium-proton exchange in spontaneously hypertensive rats. 302 56

Hindquarter reflex vasodilation (RVD delta mmHg decrease in perfusion pressure) in response to arterial pressure elevations by intravenous norepinephrine (NE) was examined in young (2 1/2-3 months) and mature (8-10 months) spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) normotensive rats to ascertain whether maximum reflex vasodilatory capacity is altered in the developmental and/or established stages of spontaneous hypertension. The maximal RVD was not significantly different in young or mature SHR (young 26.2 +/- 1.9 and mature 36.2 +/- 3.2) compared to age-matched WKY controls (young 23.9 +/- 1.8 and mature 29.6 +/- 2.3) (P greater than 0.05 between SHR vs. WKY at both ages). However, the rise in mean systemic arterial pressure by NE which produced maximal RVD was greater in mature SHR (116.0 +/- 7.4 mmHg) than in WKY controls (78.3 +/- 6.2 mmHg) (P less than 0.01), whereas no such differences were found between young SHR (85.1 +/- 6.5 mmHg) and its WKY controls (87.5 +/- 2.3 mmHg). There was no difference in the dose of NE that required maximal responses of reflex vasodilation in young or mature SHR compared to WKY controls. In each age group of SHR or WKY rats, RVD was linearly related to the arterial pressure increments. The slope (a +/- SEM) of the regression line for the correlation between the pressure rises and resultant RVD was similar in young SHR (a = 0.424 +/- 0.061) and WKY controls of (a = 0.458 +/- 0.013). In contrast, the slope of the regression line for these two parameters in mature SHR (a = 0.250 +/- 0.004) was significantly smaller than that of either WKY controls (a = 0.364 +/- 0.010) or young SHR (P less than 0.01). The direct hindquarter vasodilation of mature SHR in response to intra-arterial administration of histamine or nitroglycerin was not different compared to that of WKY controls. The results indicate an unaltered maximum hindquarter reflex vasodilatory capacity during the developmental and established stages of genetic hypertension in SHR. An additional finding in the present study was the abnormal responsiveness of the baroreceptor reflex vasodilator system of mature SHR to a wide range of arterial pressure elevations. This abnormal responsiveness may contribute to the maintenance of high blood pressure in the established stage of hypertension.
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PMID:Unaltered maximum reflex vasodilatory capacity of the perfused hindquarters of spontaneously hypertensive rats. 679 34

The transgenic rat TGR(mRen2)27 is a new monogenetic model in hypertension research that develops fulminant hypertension after the mouse Ren-2d renin gene has been integrated into its genome. To evaluate the molecular mechanism of development of hypertension in this animal model, we measured cytosolic free sodium concentration in intact lymphocytes from seven transgenic rats and eight age-matched normotensive Sprague-Dawley rats using the novel sodium-sensitive fluorescent dye sodium-binding benzofuranisophthalate. Resting cytosolic sodium was significantly higher in transgenic rats compared with Sprague-Dawley rats (31.7 +/- 2.2 versus 18.2 +/- 0.4 mmol/L, mean +/- SEM, P < .001). Inhibition of Na,K-ATPase by 0.5 mmol/L ouabain for 5 minutes significantly increased lymphocytic cytosolic sodium in Sprague-Dawley rats to 36.5 +/- 3.4 mmol/L (P < .001 compared with resting value), whereas no significant change could be observed in transgenic rats (35.4 +/- 0.6 mmol/L), indicating that Na,K-ATPase is less responsive in transgenic rats. The Na,K-ATPase activity from erythrocytes was measured with an enzyme-linked assay. Na,K-ATPase activity was significantly reduced in transgenic rats compared with Sprague-Dawley rats (4.0 +/- 0.3 versus 8.1 +/- 0.6 U/L, P < .001). We concluded that reduced Na,K-ATPase activity leads to elevated cytosolic sodium in this model of genetic hypertension.
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PMID:Increased cytosolic sodium and reduced Na,K-ATPase activity in transgenic rats. 828 58