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Effect of Hypertension on the Occurrence of Micro-hemorrhage in the Pancreatic Islet of Dahl Salt-sensitive Rats
Authors:Masako Imaoka  Ayako Sayama  Takami Suzuki  Toshimasa Jindo  Atsushi Sanbuissho
Affiliation:Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., 1-16-13, Kita-Kasai, Edogawa-ku, Tokyo 134-8630, Japan.
Abstract:The effect of hypertension on the occurrence of micro-hemorrhage in the pancreatic islet, known to be observed in Sprague-Dawley (SD) rats spontaneously, and endothelial markers were investigated in male Dahl-Iwai salt-sensitive (DIS, derived from SD rats), salt-resistant (DIR), and SD rats. DIS and DIR rats were fed 8% NaCl-containing diet to induce hypertension, with blood pressure measurement once a week, euthanized at 6, 8, or 12 weeks of age, and subjected to the measurement of plasma nitric oxide (NO) and von Willebrand factor (vWF) concentrations combined with histopathological examinations and immunohistochemical detections of vWF in the pancreas and kidney. As a result, hypertension was observed from 7 through 12 weeks of age in DIS rats. At 12 weeks of age, only DIS rats showed decreased plasma NO and increased vWF, indicating endothelial abnormality in the body. Histopathologically, micro-hemorrhage in the islet was observed with a similar incidence and severity in SD and DIS rats aged 12 weeks, and vWF was immunohistochemically localized in the islet endothelium with similar reactivity between age-matched SD rats. On the other hand, in the kidney, glomerular sclerosis was observed in DIS rats aged 12 weeks and accompanied broad stainability of vWF in the sclerotic glomerulus, including endothelium. In conclusion, there was no enhancement/exaggeration in the micro-hemorrhage in the pancreatic islet of hypertensive DIS rats in comparison with that in SD rats under the present experimental conditions. It is suggested that hypertension is not related to the occurrence of islet micro-hemorrhage, spontaneously observed in SD rats.
Keywords:Dahl-Iwai salt-sensitive rat   hypertension   pancreatic islet   endothelium   Sprague-Dawley rat
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