Sham-operated Wistar-Kyoto Rats Research Articles

Serum 25-hydroxyvitamin D is associated with renal fi brosis (experimental study)

INTRODUCTION. Vitamin D deficiency is commonly observed in patients with chronic kidney disease (CKD) due to decreased biosynthesis of 1,25(OH)2D3 in damaged renal tubules and increased catabolism of 1,25(OH)2D3 and 25OHD3. There is a growing evidence that vitamin D deficiency may contribute to impaired kidney function. Interventional studies have shown that vitamin D and its analogs attenuate the progression of renal fibrosis in experiment, and reduce proteinuria in patients with CKD. The renoprotective effects of vitamin D go far beyond its classical role in maintaining bone and mineral metabolism, which is a result of its pleiotropic action. THE AIM: to investigate the association between 25OH-hydroxyvitamin D (25OHD) level and renal fibrosis in spontaneously hypertensive rats (SHR) with early stages of experimental CKD.MATERIAL AND METHODS. Systolic blood pressure (BP), proteinuria, albuminuria, creatinine (Cr), urea (Ur), inorganic phosphate (Pi), 25OHD in serum were measured in nephrectomized (NE) and sham operated (SO) spontaneously hypertensive rats SHR (follow-up period 2, 4 and 6 months) and SO Wistar Kyoto rats (follow-up period 2 months), morphological light-optical study of kidney tissue was performed.RESULTS. The experimental model corresponded to the initial stages of CKD (Ur: 6.64 – 13.36 mmol/L). A significant increase in the area of renal fibrosis in animals with NE correlated with an increase in blood pressure (r = 0.51, p <0.001), serum Cr (r = 0.76, p <0.001), and albuminuria (r = 0.64, p <0.001) and proteinuria (r = 0.78, p <0.001) and a decrease in the concentration of 25OHD in serum (r = -0.67, p <0.001). In multiple regression analyzes, a reliable association of fibrosis with 25OHD was maintained (β = -0.28, p = 0.012). In addition, in ROC-analysis the largest value of the area under the curve was obtained for 25OHD (AUC = 0.95) to detect interstitial fibrosis more than 10 %.CONCLUSION. 25OHD depression at the initial stages of experimental CKD and hypertension is independently associated with the development of renal fibrosis.

Influence of Transplantation of Parathyroid Glands on Blood Pressure Development in Stroke Prone Spontaneously Hypertensive Rats and in Normotensive Wistar Kyoto Rats

The influence of the parathyroid glands (PTG) on the development of high blood pressure (BP) in stroke prone spontaneously hypertensive (SHR/SP) and Wistar Kyoto (WKY) rats has been studied. After ablation of their own PTG's SHR/SP received PTG's from WKY rats and vice versa. After transplantation (TRPL) a normal calcium and parathyroid hormone (PTH) status was preserved during the whole observation period. One group of animals received a high salt diet (8% NaCl) for 4 weeks after transplantation, the other group received a normal rat chow for 3 months. In SHR/SP, which had PTG-transplants from WKY rats, the development of BP was clearly attenuated compared to sham operated rats in both experimental groups. WKY rats with PTG's from SHR/SP became hypertensive after two weeks during salt loading and after six weeks under normal diet. Sham operated WKY rats remained normotensive. The results demonstrate that the parathyroid gland is involved in the pathogenesis of hypertension, but the only known secretory product of PTG's parathyroid hormone, seems not to be responsible for these effects.

Spontaneous hypertension is primarily the result of sympathetic overactivity and immunologic dysfunction.

Overactivity of the sympathetic nervous system and immunologic dysfunction have been shown to contribute to development and maintenance of hypertension in the Okamoto spontaneously hypertensive rat (SHR). In this study, the combined effects of reduction in sympathetic activity and immunologic manipulation on spontaneous hypertension have been determined. Neonatal SHRs received sham implants or implants of thymic tissue from Wistar donor rats. In addition, the thymus-implanted SHRs underwent bilateral renal denervation when they were 6 weeks old. At the same time, the sham-implanted SHRs underwent sham renal denervation. The denervations or sham operations were repeated when the SHRs were 9, 12, 15, and 18 weeks old. Wistar-Kyoto (WKY) rats also underwent serial sham renal denervations. Tail-cuff pressure measurements indicated that approximately 75% of the chronic hypertension in the SHRs was prevented by the combination of thymic implants and renal denervations. Direct arterial pressure measurements confirmed these results; when the rats were 21 weeks old, mean arterial pressure averaged 177 +/- 5.5 mm Hg in sham-operated SHRs, 134 +/- 2.7 mm Hg in implanted, denervated SHRs, and 121 +/- 2.1 mm Hg in sham-operated WKY rats. These data indicate that overactivity of the sympathetic nervous system and immunologic dysfunction account for the majority of the hypertension in the Okamoto SHR.