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The purpose of cyclooxygenase -2 (cyclooxygenase-2, COX-2) expression in the kidney structural, involved in the physiology and pathophysiology of the kidney function regulator. The clinical study found that some groups of people using the selective COX-2 inhibitors (COX-2 selective inhibitors, coxibs) can kidney side effects such as hypertension, edema, the exact mechanism is unknown. Spontaneously hypertensive rats (spontaneously hypertensive rat, SHR) is a good model for the study of human essential hypertension, the purpose of this experiment is to water and sodium metabolism and blood pressure changes observed after the use of coxibs different salt load SHR rats explore blocking COX-2 kidney sodium and water metabolism and blood pressure regulation with a view to screening of risk factors to guide clinical use of coxibs side effects for special populations use caution. 8-week-old male SHR rats and 10 each in control WKY rats were randomly divided into low salt group (SHR coxib LS group, in WKY coxib LS) and high-salt group the (SHR coxib HS group, WKYcoxib HS group), 5 in each group. After the beginning of the experiment, given daily celecoxib gavage (25mg/kg/d), the first five days, all rats were utilized, are the low-salt diet (containing NaCl 0.04%). The first six days of high-salt group to high salt (containing NaCl 8%) diet, low-salt group three days to continue the low-salt diet. Records the daily dietary intake, detecting the basis of the state, the use of celecoxib, the different salt load after rat tail artery systolic blood pressure, blood concentration of Na ~, 24-hour urine output (urine volume, and UV), 24-hour urinary sodium excretion (urine sodium excertion, UNa) excretion and urine aldosterone levels by immunohistochemistry and Western blot method to detect kidney skin, medullary expression of COX-1 and COX-2 protein expression. Results WKY rats taking celecoxib 5 days later, after a high-salt diet compared with baseline systolic blood pressure (systolic blood pressure, SBP) showed no change. Regardless of the basis of the state, celecoxib5 days or salt load after 3 days, the SBP of SHR rats high salt diet, low-salt diet group was significantly higher than WKY rats the same diet the same point in time. More significant taking celecoxib 5 days later, each group of SHR SBP increased but high-elevated SBP of SHR rats after the high-salt diet over a low-salt diet group (changes in blood pressure values ??SHRcoxib LS 4.06 ± 1.49 mmHg, SHR coxib HS 9.69 ± 3.31 mmHg, P <0.05). Sodium concentration in WKY rats and SHR rats with low-salt diet group no significant difference (SHR the coxib LS144.75 ± 8.54 mmol / L, WKY coxib LS 137.25 ± 7.41 mmol / L, P> 0.05), but high SHR rats sodium concentration of the salt diet group was significantly higher than WKY rats with high salt diet group (SHRcoxib HS158.20 ± 9.44 mmol / L, WKY coxib HS the coxib LS group 143.75 ± 9.00 mmol / L, P <0.05), compared with SHR significantly liter high. With each of the basis of the state, taking celecoxib 5 days compared to WKY rats and SHR rats UV and UNa after the high-salt diet significantly increased, but no significant difference between the two high-salt group. The plasma aldosterone detection WKY coxib HS group is below the WKY coxib LS group (were 0.64 ± 0.09ng/ml, the 1.10 ± 0.31ng/ml, P <0.05), and SHR rats no difference between the two groups (SHRcoxib LS 0.61 ± 0.05ng/ml, SHR coxib HS 0.74 ± 0.16ng/ml, P> 0.05). COX-1 is mainly expressed in the kidney glomerular collecting duct, use of celecoxib and different salt load rats cortex and medulla, COX-1 protein expression was no significant difference. COX-2 in the kidney is mainly expressed in the macula densa, cortical medullary ascending limb coarse segment and marrow stromal cells, low-salt diet and WKY rats renal cortical expression of COX-2 to a high-salt diet group was significantly increased SHR rats are no changed. WKY rats in the high-salt diet significantly increased renal medullary COX-2 expression was lower salt diet group, but no significant changes in the SHR rats. Western blot confirmed given celecoxib, WKY rats, in the case of a low-salt diet renal cortical COX-2 protein levels were significantly increased, and WKY rats after renal medullary COX-2 protein levels were significantly increased in the high-salt diet, but in SHR different salt load group application celecoxib renal cortex and medulla COX-2 protein level was no significant difference. Conclusion the SHR rats applications celecoxib elevated blood pressure, elevated after a high-salt diet more significantly, accompanied by kidney COX-2 expression regulation defects, suggesting that the kidney COX-2 is involved in the spontaneously hypertensive rat (SHR) of water and sodium metabolism and blood pressure regulation, clinical on should be used with caution in patients with hypertension background coxibs.
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