| ObjectiveTo investigate the relationship between hypertension and bone metabolism by measuring the bone mineral density (BMD) and trabecular microarchitecture and bone turnover markers in serum such as PINP and CTX in spontaneously hypertensive rats(SHR) and Wistar-Kyoto rats (WKY).MethodsEight female SHRs and eight female WKY rats(11-week-old) were selected. All rats were acclimatized for 1 week. Then body weight and blood pressure were measured every two weeks, the total is 14 weeks. Rats were executed after blood samples were withdrawn from inferior vena cava. Serum was extracted and saved at-80? for measuring calcium, phosphorus, alkaline phosphatase (ALP), Procollagen I N-terminal Propeptide (PINP), C-terminal cross-linked telopeptides of type 1 collagen (CTX). The right side of proximal tibia were fixed in 10% formaldehyde for measuring bone mineral density (BMD) and trabecular microarchitecture. BMD and microarchitectural analyses were performed by micro-computed tomography (micro-CT).Results1. Blood pressure in SHR are significantly higher than that in WKY, and progressive rise along with the increase of age (p=0.000). Body weight in SHR is lower than that in WKY at the same age (p=0.000)2. Serum concentrations of PINP and CTX were increased, BMD was decreased, trabecular microarchitecture were damaged (showed that BV/TV\Tb.Th and Tb.N were decreased, Tb.Sp and SMI were increased) in SHR compared with those in WKY (p<0.05)3. The correlation analysis showed that there was positive correlation between the BV/TV?Tb.N?Tb.Th and BMD, negative correlation between hypertension, blood pressure and BMD. Multiple linear regression analysis showed that Tb.N, hypertension and blood pressure are independent influence factors of BMD.ConclusionCompared to WKY with normal blood pressure, the rate of bone turnover increased, BMD decreased, microarchitecture were damaged in SHR. Taken together, hypertension may induce the incidence of osteoporosis.ObjectiveTo investigate the effect of commolly prescribed antihypertensive agents on bone metabolism, we employed an ovariectomized (OVX) model of estrogen deficiency in spontaneously hypertensive rats (SHR), which was the most suitable animal model that mimics postmenopausal osteoporosis with hypertension in humans. Bone mineral density (BMD) and microarchitecture were evaluated by micro-computed tomography (micro-CT). At the same time the serum concentrations of Procollagen ? N-terminal Propeptide (PINP) and C-terminal cross-linked telopeptides of type 1 collagen (CTX) were detected. All in all, we examined the effect of different antihypertensive agents on bone health from three aspects of bone quantity, bone quality and bone metabolism.Methods42 healthy female spontaneously hypertensive rats, non pregnant,11 weeks old, were randomly divided into 7 groups(n= 6 for each group). Group 1 (sham), sham-operated+drinking water(1ml); Group 2 (control), OVX + drinking water(1ml); Group 3 (hydrochlorothiazide), OVX + hydrochlorothiazide (10 mg/kg body weight); Group 4 (metoprolol), OVX + metoprolol (50 mg/kg body weight), Group 5 (amlodipine), OVX + amlodipine (5 mg/kg body weight), Group 6 (valsartan), OVX + valsartan (30 mg/kg body weight), and Group 7 (benazepril), OVX + benazepril (10 mg/kg body weight). All rats were acclimatized for 1 week. Then bilateral ovariectomy or sham operation was applied. All drugs were given once daily by intragastric administration from day 14 after operation for 12 weeks. After 12 weeks of continuous administration, the mice were executed after blood samples were withdrawn from inferior vena cava. Uterine wet weight, serum estradiol (E2), calcium, phosphorus, alkaline phosphatase (ALP), PINP and CTX were measured. Micro CT was applied to determine the bone mineral density and cancellous bone microarchitecture of the right tibia.Results1. Uterine wet weight and E2 results Compared with the sham group, uterine wet weight and E2 levels were decreased in ovariectomized group. The difference was statistically significant (p<0.001), indicating the success of ovarian surgery.2. BMD results(1) Compared with the sham group, BMD was significantly decreased (p<0.001) in the control group, which showed that the postmenopausal osteoporosis model was successful.(2) Compared with the control group, the BMD was significantly higher in the hydrochlorothiazide and benazepril groups(p<0.001). There was no significant difference between hydrochlorothiazide and benazepril treatment group and the sham group.(3) The BMD of the metoprolol, amlodipine and valsartan group were significantly lower than those in the sham group (p<0.001), but there was no significant difference compared with the control group.3. Cancellous bone microarchitecture parameters results(1) Compared with the sham group, BV/TV and Tb.N were significantly decreased (p<0.01), Tb.Sp and SMI were significantly increased in the control group (p<0.01).(2) BV/TV and Tb.N were significantly higher, Tb.Sp and SMI were significantly lower in hydrochlorothiazide group than that in the control group ((p<0.05, p<0.01), but there was no significant difference compared with the sham group.(3) Tb.N was significantly higher, Tb.Sp and SMI were significantly lower in the benazepril group than that in the control group (p<0.01,p<0.05); but there was no significant difference compared with the sham group.(4) BV/TV and Tb.N were significantly lower, Tb.Sp and SMI were significantly higher in the metoprolol or valsartan group than those in the sham group (p<0.01); but there was no significant difference compared with the control group.(5) Tb.N was significantly lower, Tb.Sp and SMI were significantly higher in the amlodipine group than those in the sham group ((p<0.01, p<0.05); but there was no significant difference compared with the control group.4. Blood biochemical markers related to bone metabolism(1) Compared with the sham group, serum centrations of PINP and CTX were significantly increased in the control group (p<0.05; p<0.001).(2) Serum centrations of PINP and CTX in hydrochlorothiazide, amlodipine or benazepril groups were significantly lower than those in the control group (p<0.05), and there was no significant difference compared with sham group.(3) Serum centrations of PINP and CTX in the metoprolol or valsartan groups were higher than those in the sham group (p<0.05), and there was no significant difference compared with control group.(4) Serum centrations of calcium, phosphorus and ALP showed no significant difference in each group.Conclusion1. Bilateral ovariectomy can induce BMD decrease, cancellous bone microstructure destruction, PINP and CTX increase in SHR, indicating the osteoporosis with high bone turn-over.2. In addition to decrease blood pressure, hydrochlorothiazide and benazepril, can effectively inhibit the decrease of BMD, destruction of bone microstructure, elevation of serum centrations of PINP and CTX, which induced by ovariectomy in SHR, thereby effectively preventing osteoporosis.3. Metoprolol, amlodipine and valsartan do not have the protective effect on osteoporosis induced by ovariectomy in SHR. |
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