Enhanced thromboxane formation by blood but not whole platelets from spontaneously hypertensive rats.

Increased serum levels of immunoreactive thromboxane B2 (iTXB2) were observed in spontaneously hypertensive rats of the Okamoto-Aoki strain (SHR) compared with normotensive Wistar-Kyoto rats (WKY). Serum iTXB2 levels in whole blood allowed to clot at 37 degrees C for 1 hour were significantly greater in SHR than WKY at 8, 16-20, and 38 weeks of age, whereas formation of iTXB2 by thrombin-stimulated whole platelets from 6 16-week-old SHR and 6 age-matched WKY was 399 +/- 44 and 377 +/- 38 ng/10(9) platelets/30 min, respectively. No significant difference in radioconversion of exogenous arachidonic acid to TXB2 was observed in whole platelets from SHR (18.2 +/- 2.5%, n = 4) and WKY (20.1 +/- 3.0%, n = 4) at 16 weeks of age. These results support the proposal that enhanced ability of blood from SHR to generate iTXB2 is independent of the stage of hypertension development. This enhancement probably depended on factors or blood elements other than platelets since no difference in formation was observed on stimulation of whole platelets.     

Norepinephrine concentration in kidneys of normotensive Wistar-Kyoto and spontaneously hypertensive rats.

Renal norepinephrine (NE) concentration was measured in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) at 7, 9, 11, and 13 weeks of age. Although the weight of kidneys was similar in the two strains of rats, renal NE concentration was significantly lower in SHR at all ages (147 +/- 9 to 175 +/- 13 ng/g for SHR, and 216 +/- 8 to 262 +/- 17 ng/g for WKY rats). The difference in renal NE concentration during this time of rapidly increasing arterial pressure in the SHR suggests that renal NE may in some way be related to the development of hypertension.     

Ontogeny of mitochondrial calcium transport in spontaneously hypertensive (SHR) and WKY rats

The current studies were designed to investigate calcium uptake by intestinal jejunal sacs as well as in intestinal mitochondria of spontaneously hypertensive rats and their genetically matched WKY control rats. Kinetics of jejunal calcium uptake by jejunal sacs of adult SHR and WKY rats showed a significant decrease in Vmax of calcium uptake in SHR (227 +/- 24 versus 423 +/- 22 nmol.g tissue-1.3 min-1) compared to WKY rats P less than 0.001. To explore the intracellular handling of calcium by the intestinal mitochondria, calcium uptake was characterized by intestinal mitochondria before (suckling and weanling periods) and after (adult period) development of hypertension. Calcium uptake by intestinal mitochondria was driven by ATP in the presence of succinate as a respiratory substrate. Calcium uptake was stimulated several fold by the presence of ATP compared to no ATP conditions. Maximal calcium uptake occurred between 15-30 min and was significantly greater in adult SHR and WKY rats compared to corresponding values in weanling and suckling rats. Maximal ATP dependent calcium uptake in adult, weanling and suckling WKY rats was significantly greater compared to corresponding mean values in each age group in SHR (P less than 0.001). Oligomycin (10 micrograms/mg protein) inhibited calcium uptake partially. Ruthenium red (0.25 microM), 1 mM sodium azide and 0.5 mM dinitrophenol inhibited calcium uptake by more than 80% in both SHR and WKY rats. Kinetic parameters for ATP stimulated calcium uptake at 10 s revealed a Vmax of 0.56 +/- 0.6, 3.46 +/- 0.23 and 3.95 +/- 0.52 nmol/mg protein/10 s in suckling, weanling and adult WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of a fructose-enriched diet on plasma insulin and triglyceride concentration in SHR and WKY rats

Significant increases (P less than 0.001) in plasma insulin and triglyceride concentrations and in blood pressure were seen when SHR and WKY rats ate a fructose-enriched diet for 14 days. However, all of the changes were significantly accentuated (P less than 0.02-0.001) in SHR rats. Specifically the increment in plasma insulin concentration following the fructose-enriched diet was 42 +/- 4 microU/ml in SHR as compared to 25 +/- 4 microU/ml in WKY rats (P less than 0.001). Plasma triglyceride concentrations also increased to a greater degree in response to fructose in SHR rats (260 +/- 24 vs. 136 +/- 20 mg/dl, P less than 0.001). Finally, the fructose-induced increase in blood pressure of 29 +/- 4 mm of Hg in SHR rats was greater (P less than 0.02) than that seen in WKY rats (19 +/- 2 mm of Hg). There was no change in plasma glucose concentration in response to the fructose diet. WKY rats gained more weight than did the SHR rats. Thus, although plasma triglyceride and insulin concentration and blood pressure increased when either WKY or SHR rats consumed a fructose enriched diet, the magnitude of these changes was greater in SHR rats.     

Maternal metabolic abnormalities in twin-to-twin transfusion syndrome at mid-pregnancy.

We report abnormal maternal laboratory parameters in twin-to-twin transfusion syndrome (TTTS) at mid-pregnancy. A retrospective chart review was undertaken of 109 patients with TTTS evaluated for placental laser surgery. Complete blood count (CBC), blood type and Rh factor, urine analysis and serum chemistry panel were obtained preoperatively, with the CBC and serum albumin repeated on the first postoperative day. The mean gestational age was 21.2+/-1.7 weeks. Initial abnormal values included hematocrit (32.1+/-3.0%), hemoglobin (11.0+/-1.03 g/dl), serum magnesium (1.71+/-0.17 mg/dl), total protein (6.08+/-0.55 g/dl) and albumin (3.06+/-0.34 g/dl). Despite minimal blood loss and conservative fluid replacement mean hematocrit, hemoglobin, and albumin were 27.3+/-2.74%, 9.3+/-0.94 g/dl and 2.56+/-0.23 g/dl, respectively on postoperative day one. Weight gain (8.0+/-5.5 lb.) and low urinary output were characteristic peri-operative events. Maternal hypoproteinemia and anemia occur in TTTS at mid-pregnancy. This may contribute independently to amniotic fluid production rates in the fetuses, and explain in part the maternal sensitivity to intravenous fluids in multiple pregnancy.     

Decrease in urinary excretion of active kallikrein in conscious young and adult spontaneously hypertensive rats

Urinary excretion of active kallikrein was determined every day (amidolytic assay) in 6 male Okamoto-Aoki spontaneously hypertensive rats (SHR) and 6 male normotensive Wistar-Kyoto rats (WKY) from ages 4 to 7 weeks and from 12 to 15 weeks. The rats were housed in individual metabolic cages and were allowed free access to food having normal sodium content and to tap water. Urinary kallikrein excretion was lower in 4-week-old SHR than in age-matched WKY (7.8 +/- 1.4 vs. 15.5 +/- 2.3 nkat/24 h respectively, P less than 0.01) at a moment when systolic blood pressure (BP) in SHR was already higher than in WKY. The slope of the increase in active kallikrein excretion from week 4 to 7 was not different for SHR and WKY (6.34 +/- 1.05 vs. 7.50 +/- 1.02 nkat/24 h-1 . wk-1 respectively). In contrast, from week 12 to 15, this slope was not significant for SHR (1.67 +/- 2.55 nkat/24 h-1 . wk-1) while it remained positive in WKY (7.36 +/- 3,44 nkat/24 h-1 . wk-1). In both SHR and WKY, urinary kallikrein excretion was directly related to BP from week 4 to 7 but the slope of the regression line was less for SHR than for WKY (0.19 +/- 0.05 vs. 0.48 +/- 0.12 nkat/24 h-1 . mm Hg respectively). From ages 12 to 15 weeks, kallikrein excretion was still related to pressure in WKY (y = 1.92 x - 180.8; r = 0.93) but not in SHR (y = 0.71 x - 81.48; r = 0.52).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of blood pressure on L-NAME-sensitive component of vasorelaxation in adult rats

The aim of this study was to investigate nitric oxide (NO) production and L-NAME-sensitive component of endothelium-dependent vasorelaxation in adult normotensive Wistar-Kyoto rats (WKY), borderline hypertensive rats (BHR) and spontaneously hypertensive rats (SHR). Blood pressure (BP) of WKY, BHR and SHR (determined by tail-cuff) was 111+/-3, 140+/-4 and 184+/-6 mm Hg, respectively. NO synthase activity (determined by conversion of [(3)H]-L-arginine) was significantly higher in the aorta of BHR and SHR vs. WKY and in the left ventricle of SHR vs. both BHR and WKY. L-NAME-sensitive component of endothelium-dependent relaxation was investigated in the preconstricted femoral arteries using the wire myograph during isometric conditions as a difference between acetylcholine-induced relaxation before and after acute N(G)-nitro-L-arginine methyl ester pre-treatment (L-NAME, 10(-5) mol/l). Acetylcholine-induced vasorelaxation of SHR was significantly greater than that in WKY. L-NAME-sensitive component of vasorelaxation in WKY, BHR and SHR was 20+/-3 %, 29+/-4 % (p<0.05 vs. WKY) and 37+/-3 % (p<0.05 vs. BHR), respectively. There was a significant positive correlation between BP and L-NAME-sensitive component of relaxation of the femoral artery. In conclusion, results suggest the absence of endothelial dysfunction in the femoral artery of adult borderline and spontaneously hypertensive rats and gradual elevation of L-NAME-sensitive component of vasorelaxation with increasing blood pressure.     

Expression and localization of angiotensin subtype receptor proteins in the hypertensive rat heart

The cellular localization of the AT(2) receptor and the regulation of its expression in hypertrophied left ventricle are not well known. We compared the expression of the cardiac AT(1) and AT(2) receptor in spontaneously hypertensive rats/Izumo strain (SHR/Izm) and Wistar Kyoto rats/Izumo strain (WKY/Izm), ages 4, 12, and 20 wk, by means of immunohistochemistry and Western blot analysis. In SHR/Izm, compared with WKY/Izm, blood pressure (161 +/- 2 vs. 120 +/- 2 mmHg at 12 wk, P 相似文献   

Na-dependent changes in intracellular Ca in spontaneously hypertensive rat hearts.

To determine whether Na/Ca exchange is altered in primary hypertension, Na-dependent changes in intracellular Ca, ([Ca]i), were measured in isolated perfused hearts from Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Intracellular Na, (Nai, mEq/kg dry wt), and [Ca]i were measured by NMR spectroscopy. Control [Ca]i was less in WKY than SHR (176 +/- 18 vs 253 +/- 21 nmol/l; mean +/- S.E., P < 0.05), whereas Nai was not significantly different. One explanation for this is that net Na/Ca exchange flux is decreased in SHR. If this hypothesis is correct, the rate of Ca uptake in SHR should be less than WKY when Na/Ca exchange is reversed by decreasing the transmembrane Na gradient. The Na gradient was reduced by decreasing extracellular Na, ([Na]o) and/or by increasing [Na]i. To increase [Na]i, Na uptake was stimulated by acidification while Na extrusion by Na/K ATPase was inhibited by K-free perfusion. Seventeen minutes after acidification, Nai had increased but was not significantly different in SHR and WKY (18.0 +/- 2.3 to 57.4 +/- 7.6 vs 20.3 +/- 0.6 to 66.5 +/- 4.8 mEq/kg dry wt, respectively). Yet [Ca]i was greater in WKY than SHR (1768 +/- 142 vs 1201 +/- 90 nmol/l; P < 0.05). [Ca]i was also measured after decreasing [Na]o from 141 to 30 mmol/l. Fifteen minutes after reducing [Na]o, [Ca]i was greater in WKY than SHR (833 +/- 119 vs 425 +/- 94 nmol/l; P < 0.05). Thus for both protocols, decreasing the transmembrane Na gradient led to increased [Ca]i in both SHR and WKY, but less increase in SHR. The results are consistent with the hypothesis that Na/Ca exchange activity is less in SHR than WKY myocardium.     

A possible explanation of genetic hypertension in the spontaneously hypertensive rat

Converting enzyme inhibitors prevent the development of hypertension and normalize arterial blood pressure in spontaneously hypertensive rats (SHR), suggesting a critical role for angiotensin II in genetic hypertension. We hypothesized that the SHR is hyperresponsive to the slow-pressor effect of angiotensin II. To test this hypothesis, 14 SHR and 14 normotensive Wistar Kyoto rats (WKY) were treated chronically with captopril (100 mg X kg-1 X day-1 in drinking water) beginning at 5 weeks of age. At 9 weeks of age, either angiotensin II (125 ng/min; 7 SHR and 7 WKY) or vehicle (7 SHR and 7 WKY) was infused for 2 weeks via an osmotic minipump implanted into the peritoneal cavity. Captopril treatment was maintained and systolic blood pressure was monitored 3 times weekly. Although systolic blood pressure was similar in SHR and WKY infused with vehicle (101 +/- 2 versus 103 +/- 5 mmHg, respectively during the second week), systolic blood pressure in SHR treated with angiotensin II was much greater than systolic blood pressure in WKY treated with angiotensin II (193 +/- 9 versus 132 +/- 11 mmHg, respectively during the second week, p less than 0.001). These results indicate that compared to WKY, SHR are remarkably more sensitive to the slow-pressor effect of chronic, low-dose infusions of angiotensin II. Our results support the hypothesis that the critical genetic defect in SHR is a change in the sensitivity to the slow-pressor effect of angiotensin II.     

Long-term effects of betamethasone on blood pressure and hypothalamo-pituitary-adrenocortical function in spontaneously hypertensive and normotensive rats

An enhanced hypothalamo-pituitary-adrenocortical (HPA) activity has been described during onset of elevated blood pressure in spontaneously hypertensive rats (SHR). An instability of the HPA axis could thus contribute to the development of hypertension in these animals. Glucocorticoid effects on blood pressure and HPA function were studied therefore in SHR and normotensive Wistar-Kyoto (WKY) and Wistar rats. Beginning at 4 weeks of age, the rats were treated with 0.1 and 0.5 microgram betamethasone per milliliter drinking water for 7 weeks. SHR and WKY responded with a significant elevation in average blood pressure. In SHR, mean blood pressure rose from 181.4 +/- 3.9 (mean +/- SEM) to 203.1 +/- 2.8 mm Hg in response to the lower dose of betamethasone and to 209.2 +/- 4.0 mm Hg in response to 0.5 microgram betamethasone per milliliter drinking water. In WKY, blood pressure increased from 134.4 +/- 3.3 to 148.2 +/- 3.0 and 157.9 +/- 4.5 mm Hg in response to the lower and higher dose of betamethasone, respectively. No significant effect was seen in Wistar rats, where the mean blood pressure values changed insignificantly from 133.8 +/- 2.1 to 136.3 +/- 3.2 and 135.6 +/- 2.4 mm Hg. Stress-induced secretion of corticosterone was significantly suppressed in a dose-dependent manner in all three strains. Stress-induced secretion of adrenocorticotropin was markedly reduced by 0.5 microgram betamethasone per milliliter in SHR and by both doses in WKY. No significant effect, however, was seen in Wistar rats. A predisposition to the hypertensiogenic actions of glucocorticoids was found therefore in SHR and WKY, but not in Wistar rats.     

Magnesium uptake by intestinal brush-border membranes of spontaneously hypertensive rats.

Magnesium uptake by intestinal brush-border membranes (BBM) was studied in duodenal and jejunal vesicles of the spontaneously hypertensive rat (SHR) and normotensive control, the Wistar-Kyoto (WKY) rat. In the duodenum, no statistical difference was evidenced between the two types of rats. By contrast, initial rates of magnesium uptake in jejunal vesicles were lower in SHR (5.4 +/- 2.1 nmol/mg protein x 10 sec) in comparison to WKY rats (11.0 +/- 2.5 nmol/mg protein x 10 sec) at a magnesium concentration of 1 mM (P less than 0.01). In jejunal BBM, kinetic analysis of magnesium uptake showed three components in WKY rats, with one being diffusional. In SHR, only two components were seen, with the diffusional one being absent. The two saturable components showed Vmax of 6.5 +/- 1.3 and 26.2 +/- 6.0 nmol/mg protein x 10 sec and apparent Km of 0.22 +/- 0.12 mM and 1.9 +/- 0.4 mM in WKY rats, and Vmax of 10.9 +/- 3.5 and 14.8 +/- 5.9 nmol/mg protein x 10 sec and apparent Km of 0.43 +/- 0.23 mM and 1.3 +/- 0.2 mM in SHR. Only the component with the lowest apparent affinity appeared statistically different in SHR as compared with WKY rats for both Vmax and apparent Km (P less than 0.05). Time course evolution of magnesium uptake in jejunal BBM indicated, by extrapolation at zero time, that 2.5 and 5.1 nmol magnesium/mg protein in SHR and WKY rats, respectively, would be in the bound state. The study of the influence of medium osmolarity on 60-min magnesium uptakes was also indicative of a smaller binding compartment in jejunal BBM of SHR (3.70 and 8.26 nmol/mg protein in SHR and WKY rats, respectively); at the four osmolarities assayed, the 60-min uptakes were significantly lower in SHR as compared with WKY rats (P less than 0.01). From 60-min glucose uptakes, a smaller volume of jejunal BBM vesicles was determined for SHR as compared with WKY rats (0.34 +/- 0.06 and 0.63 +/- 0.17 microliter/mg of protein in SHR and WKY rats respectively, P less than 0.05), this volume being significantly augmented by the presence of 1 mM MgCl2 (0.48 +/- 0.05 and 1.27 +/- 0.02 microliter/mg of protein in SHR and WKY rats respectively, P less than 0.01). These results suggest that magnesium uptake and binding by jejunal BBM are altered in SHR in comparison to WKY rats, implying a possible role of the small intestine in the abnormalities of magnesium metabolism in genetic hypertension.     

Erythropoietin increases cytosolic free calcium concentration and thrombin induced changes in cytosolic free calcium in platelets from spontaneously hypertensive rats

Using fura-2 cytosolic free calcium concentrations were measured in intact washed platelets from 9 spontaneously hypertensive rats (SHR) and from 9 age-matched normotensive Wistar-Kyoto rats (WKY). In resting platelets cytosolic free calcium concentration was significantly higher in SHR than in WKY (171.8 +/- 64.4 nM vs 93.1 +/- 59.0 nM, p less than 0.05). After preincubation with erythropoietin cytosolic free calcium concentration was significantly higher in SHR than in WKY (197.5 +/- 83.2 vs 93.0 +/- 60.1, p less than 0.01). Using platelets from SHR erythropoietin increased mean resting cytosolic free calcium concentration by 14.9% (p less than 0.05) and mean thrombin induced changes of cytosolic free calcium by 58.3% (p less than 0.01). In contrast, erythropoietin caused no significant increase in the resting calcium concentration or in thrombin induced changes of cytosolic free calcium in platelets from WKY. It is concluded that erythropoietin is involved in the pathogenesis of hypertension by elevating cytosolic free calcium concentration.     

自发性高血压大鼠多组织炎症状态

高血压是一种慢性血管性疾病,易累及肾、肝、心、脑等组织,引起脑卒中和心、肾损害等并发症.本研究对高血压时肾、肝、心、脑等组织的炎症状态进行了观察.实验采用自发性高血压大鼠(spontaneously hypertensive rat,SHR)和正常血压的Wistar-Kyoto(WKY)大鼠,用RT-PCR和Western blot法观察肾、肝、心、脑等组织炎症相关因子IL-1p、TNFα、ICAM-1、iNOS、C/EBPδ和PPARγ的基因表达;紫外分光光度法观察蛋白质羰基化水平和FRAP法检测组织总抗氧化能力.结果显示(1)SHR组织炎症相关因子表达较对照WKY增强,除IL-1βmRNA在肝和脑的增加不明显外,其余均有显著性差异(P＜0.05);(2)SHR和WKY大鼠肾、心、脑蛋白质羰基化水平(nmol/mg蛋白)分别为8.93±1.08和2.27±0.43、2.23±0.23和0.17±0.02、13.42±1.10和5.72±1.01,SHR明显增加(P＜0.05);而肝脏蛋白质羰基化水平无明显变化;(3)SHR肾、肝、心、脑总抗氧化能力水平显著低于WKY大鼠(P＜0.05).以上结果表明,SHR多个组织(肾、肝、心和脑)均存在炎症因子被诱导和氧化应激反应等明显的炎症状态,提示炎症可能在高血压及其并发症的病理改变中起重要作用.     

Vascular effects of 15-F2t-isoprostane in spontaneously hypertensive rats

F2-isoprostanes are a family of compounds derived from arachidonic acid by free radical-catalyzed peroxidation. Among F2-isoprostanes, 15-F2t-IsoP is a vasoconstrictor in animal and human vascular beds. Several recent studies found increased 15-F2t-IsoP levels in animal models of hypertension. However, no data is available on the vascular effect of 15-F2t-IsoP in such models. The contractile responses of 15-F2t-IsoP (10(-9) to 3 x 10(-5) mol/L) were tested on rat thoracic aortic rings in spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto (WKY) rats. The contraction induced by 15-F2t-IsoP was not significantly different in aortic rings from WKY rats and SHR (Emax 139% +/- 5% vs. 134% +/- 6%, respectively) and was mediated through thromboxane A2-prostaglandin H2 receptor activation as shown by the rightward shift of the concentration-contraction curves in presence of GR 32191, a specific thromboxane A2-prostaglandin H2 receptor antagonist. Endothelial denudation increased the maximal contraction compared to intact rings induced by 15-F2t-IsoP in both WKY rats (170% +/- 20% vs. 139% +/- 5%, p < 0.05) and SHR (194% +/- 11% vs. 134% +/- 6%, p < 0.01), whereas pretreatment with Nomega-nitro-L-arginine (10(-4) mol/L) or with indomethacin (10(-5) mol/L) increased the maximal contraction to 15-F2t-IsoP in WKY rats but not in SHR. SHRs treated with an angiotensin-converting enzyme inhibitor, enalapril, for four weeks showed decreased maximal contraction to 15-F2t-IsoP in vessels with and without endothelium compared with untreated SHR. In conclusion, 15-F2t-IsoP-induced vasoconstriction is similar in SHR compared with WKY rats. Endothelium modulates 15-F2t-IsoP contraction in both strains. However, whereas this effect is mediated through nitric oxide- and cyclooxygenase-dependent pathways in WKY rats, other mediators are implicated in SHR.     

Vasopressin receptors and inositol trisphosphate production in blood vessels of spontaneously hypertensive rats

To understand the regulation of vasopressin (AVP) receptors in spontaneous hypertension, we investigated the pressor response of AVP in the perfused mesenteric vasculature, AVP binding sites in the membrane preparation of the same vascular bed, and the production of inositol trisphosphate (InsP3) stimulated by AVP in the aorta of spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), and Wistar rats (WR) at different ages (4-16 weeks). Plasma AVP concentrations were similar in SHR, WKY, and WR at all ages. The density of AVP vascular binding sites was significantly higher in WKY than in SHR and WR at 12 weeks. Receptor affinity was similar in all strains. The pressor response of the mesenteric vasculature to AVP was similar in the three strains of rats at 4 weeks (prehypertensive stage) and increased progressively in SHR compared with WKY and WR at 8 and 12 weeks of age by 43 and 35%, respectively, and by more than 80% at 16 weeks of age (established hypertensive stage). There was no difference in vascular sensitivity to AVP. A significantly increased pressor response to a supramaximal dose of norepinephrine was also found at 16 weeks in SHR, but not in younger rats. InsP3 production in the aorta in response to AVP was increased in SHR at 8, 12, and 16 weeks, compared with WKY and WR. These results suggest that the vascular response to AVP is increased in SHR, in spite of decreased or normal density of binding sites compared with WKY or WR.(ABSTRACT TRUNCATED AT 250 WORDS)     

骨桥蛋白增强自发性高血压大鼠血管外膜成纤维细胞的迁移活性

血管外膜成纤维细胞迁移参与形成新生内膜是一些血管疾病的共同发病过程。研究高血压动物模型的外膜成纤维细胞是否与对照组不同将有利于阐述高血压血管重塑的机制。本实验比较自发性高血压大鼠(spontaneously hy-pertensive rats,SHR)与正常对照大鼠(Wistar-Kyoto rats,WKY)的血管外膜成纤维细胞在体外培养条件下迁移能力的差别,并对其机制进行了探讨。采用大鼠胸主动脉的培养血管外膜成纤维细胞,用Transwell技术测定培养细胞的迁移能力。用实时定量PCR技术检测mRNA表达。结果表明,在血清和bFGF趋化作用下,SHR培养血管外膜成纤维细胞的迁移活性显著强于WKY(每个视野平均迁移细胞数目,血清:35.20±5.26 vs 22.2±3.27,P<0.05;bFGF:30.23±4.54vs 19.20±4.47,P<0.05)。进一步研究发现,SHR培养血管外膜成纤维细胞中的骨桥蛋白(osteopontin,OPN)mRNA水平显著高于WKY(1863.23±43.91 vs 326.24±68.29,P<0.01)。反义OPN(100 μmol/L)对血清诱导的SHR血管外膜成纤维细胞迁移有抑制作用(每个视野平均迁移细胞数目 38.60±5.98 vs 26.61±3.84,P<0.05)。而正义及错配义OPN组均无此效应。反义OPN对SHR细胞迁移的抑制作用呈浓度依赖性。上述结果证实SHR培养血管外膜成纤维细胞的迁移能力强于WKY,OPN在细胞迁移中     

Myocardial hypertrophy of normotensive Wistar-Kyoto rats

In our studies with spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar rats, we observed normotensive WKY rats with cardiac hypertrophy determined by a greater left ventricular (LV) mass (LVM)-to-body weight (BW) ratio (LVM/BW) than that of normotensive Wistar rats. Thus we compared the following parameters in SHR, WKY, and Wistar rats: LVM/BW, cell capacitance as index of total surface area of the myocytes, length, width, and cross-sectional area of cardiac myocytes, LV collagen volume fraction, and myocardial stiffness. The LVM/BW of WKY (2.41 +/- 0.03 mg/g, n = 41) was intermediate between SHR (2.82 +/- 0.04 mg/g, n = 47) and Wistar rats (1.98 +/- 0.04 mg/g, n = 28). A positive correlation between blood pressure and LVM was found in SHR, whereas no such relationship was observed in WKY or Wistar rats. Cell capacitance and cross-sectional area were not significantly different in SHR and WKY rats; these values were significantly higher than those of Wistar rats. The cell length was smaller but the width was similar in WKY compared with SHR. Papillary muscles isolated from the LV of WKY and SHR were stiffer than those from Wistar rats. Consistently, a greater level of myocardial fibrosis was detected in WKY and SHR compared with Wistar rats. These findings demonstrate blood pressure-independent cardiac hypertrophy in normotensive WKY rats.     

Sexual dimorphism in the renin-angiotensin system in aging spontaneously hypertensive rats

In young adult spontaneously hypertensive rats (SHR), mean arterial pressure (MAP) is higher in males than in females and inhibition of the renin-angiotensin system (RAS) eliminates this sex difference. After cessation of estrous cycling in female SHR, MAP is similar to that in male SHR. The purpose of this study was to determine the role of the RAS in maintenance of hypertension in aging male and female SHR. At 16 mo of age, MAP was similar in male and female SHR (183+/-5 vs. 193+/-8 mmHg), and chronic losartan (40 mg.kg-1.day-1 po for 3 wk) reduced MAP by 52% (to 90+/-8 mmHg, P<0.05 vs. control) in males and 37% (to 123+/-11 mmHg, P<0.05 vs. control) in females (P<0.05, females vs. males). The effect of losartan on angiotensin type 1 (AT1) receptor blockade was similar: MAP responses to acute doses of ANG II (62.5-250 ng/kg) were blocked to a similar extent in losartan-treated males and females. F2-isoprostane excretion was reduced with losartan more in males than in females. There were no sex differences in plasma renin activity, plasma angiotensinogen or ANG II, or renal expression of AT1 receptors, angiotensin-converting enzyme, or renin. However, renal angiotensinogen mRNA and protein expression was higher in old males than females, whereas renal ANG II was higher in old females than males. The data show that, in aging SHR, when blood pressures are similar, there remains a sexual dimorphism in the response to AT1 receptor antagonism, and the differences may involve sex differences in mechanisms responsible for oxidative stress with aging.