The Effects Of Testosterone On Function And Structure Of Kidney And Artery In Spontaneously Hypertensive Rats

Objectives:In this study, we detect the function and structure changes in kidney and artery to explore the effects of testosterone on function and structure of target organs in spontaneously hypertensive rats with injecting physiological doses of testosterone propionate intramuscularly.Methods:Thirty-six SHR and Wistar-Kyoto rats (WKY) of ten weeks old were ovariectomized and assigned to three groups randomly:ovariectomized (OVX) group, estrogen supplement after ovariectomy (OVX+EB) group and androgen intervention after ovariectomy (OVX+TP) group. They accepted intramuscular injection of tea oil0.5ml/(kg.2d), estradiol benzoate(EB)0.25mg/(kg.2d) and testosterone propionate (TP)3mg/(kg-2d) respectively for8weeks. OVX group was blank control. OVX+EB group serves as positive control. The tail artery systolic blood pressure (SBP) was measured at the beginning,4th and8th weekend of our study respectively by tail cuff method. The rats were put into metabolic cages and the urine of24hours was collected, then tested urinary albumin and urinary creatinine concentration by ELISA, and calculate the ratio of protein to creatinine. At last, all the rats were anesthetized and killed, then determine serum testosterone, estradiol and progesterone concentrations by ELISA, separate the right kidney and measure the weight and perform HE staining in renal and vascular to observe pathological changes. The relaxation responses of rat mesenteric artery preconstricted by phenylephrine (PE) to acetylcholine (Ach) or sodium nitroprusside (SNP) were tested with the help of DMT wire myograph system.Results:1.Compared with SBP of corresponding group at the beginning of our study, SBP of both OVX and OVX+TP WKY and SHR increased continuously during8weeks experiment (P<0.05). Estrogen supplement can inhibit the SBP increase (P<0.05), while TP intervention can elevate SBP of both ovariectomized SHR and WKY further. Compared with SBP of corresponding OVX at8th weekend, SBP of OVX+TP group SHR and WKY increased significantly (P<0.01) and SBP of estrogen supplemented SHR and WKY decreased (P<0.05)2. Urinary albumin concentration and the ratio of albumin to creatinine of OVX+TP SHR was much higher than OVX SHR and OVX+TP WKY (P<0.01), While TP supplement can only increase urinary albumin concentration in WKY significantly (P<0.01), but had no effect on the ratio of protein to creatinine (P>0.05). And TP intervention can increase the single kidney weight (P<0.05) and the ratio of kidney to body weight (P<0.01) of both SHR and WKY. OVX and OVX+TP SHR and WKY group showed renal tubular injury of different degrees. What’s more, the changes in TP intervention group were more serious, especially for OVX+TP SHR;3. Estrogen supplement can significantly improve Ach-induced vasodilation of mesenteric arteries in ovariectomized WKY and SHR rats. Compared with SHR+OVX, the mesenteric artery vasodilation induced by Ach in SHR+OVX+TP group were much weaker, while the differences between WKY+OVX+TP and WKY+OVX are relatively smaller. The differences of rat mesenteric arteries response to sodium nitroprusside were not statistically significant. These results indicate that testosterone may weaken endothelium-dependent relaxation of WKY and SHR, especially for SHR. Testosterone can promote smooth muscle hypertrophy of aorta in TP intervented SHR and WKY. The changes in SHR were more obvious, but there are no significant pathological changes in all groups.Conclusions:1. Injection of physiological dose of testosterone intramuscularly to ovariectomized SHR rats promotes the elevation of systolic blood pressure;2. Injection of physiological dose of testosterone intramuscularly to ovariectomized SHR rats exacerbates the injury of kidney function and changes of kidney structure;3. Injection of physiological dose of testosterone intramuscularly to ovariectomized SHR rats weaken endothelium-dependent relaxation of mesenteric artery and promotes hypertrophy of smooth muscle in SHR;4. Physiological doses of testosterone can also result in elevation of systolic blood pressure and dysfunction and structure changes of kidneys and arteries in ovariectomized WKY rats, but the changs are much slighter than that of SHR.