Effect of clonidine on renal alpha-adrenergic receptors and development of hypertension in Dahl-Iwai salt-sensitive rats.

背景：我们报道了高盐饮食的Dahl-Iwai盐敏感（DIS）大鼠的α - 2肾上腺素能受体密度在脑干下部较低，而在肾基底外膜较高，盐和受体调节之间的相互作用可能是盐诱导DIS大鼠高血压发展的关键（临床实验Hypertens， press）。在本研究中，我们评估了可乐定是否能抑制高血压的发展，并阐明了可乐定对DIS大鼠肾基底外膜α 1-和α 2肾上腺素受体的影响。方法：4周龄Dahl-Iwai盐敏感大鼠分为3组，分别饲喂高盐（8.0%NaCl）至8周龄。G1：对照组只喝蒸馏水，G2：可乐定组只喝0.4mg/L可乐定溶液，G3：戒断组前2周只喝可乐定溶液，后2周只喝蒸馏水。8周龄以上取尿，然后用Percoll密度法取肾基底外膜。采用3H-prazosin和3h - rauwolsciine检测肾上腺素受体α 1和α 2的密度。采用尾袖法测量收缩压（SBP）。用高效液相色谱法测定尿儿茶酚胺含量。结果：6周龄时，G1组sbp（160<正负>0.8，平均<正负>SEM）高于G2组（144<正负>0.7）和G3组（145<正负>0.9）。停用可乐定后G3的收缩压在8周龄时上升至与G1相同的水平（G1: 229<正负>3.6,G3: 227<正负>3.6），而G2的收缩压（198<正负>0.6）保持低于G1和G3。G3组尿去甲肾上腺素（NA）（639<正负bbb37 ng/d）高于G1组（441<正负bbb38 ng/d）和G2组（236<正负>0 ng/d）。G3组尿肾上腺素（AD）（152<正负>9 ng/d）高于G2组（76<正负bbb9 ng/d）。G3组（alpha1 239<正负bbbb4， alpha2 504<正负>26 fmol/mg蛋白）比G1组（373<正负>39,737<正负>54）和G2组(3)α 1-和α 2-肾上腺素受体密度均低于G1组（373<正负>39,737<正负>54）和G2组(3)结论：(1)氯定治疗未能抑制DIS高血压的发展。(2)停用氯定使DIS大鼠尿儿茶酚胺升高，肾基底外膜α 1-和α 2-肾上腺素受体密度降低。少

Background : We reported that alpha2-adrenoceptor densities in Dahl-Iwai salt-sensitive (DIS) rats rats fed a high-salt diet showed lower levels in the lower brainstem and higher levels in the renal basolateral membranes and the interaction between salt and receptor regulation in the early phase of life may be essential for the development of salt-induced hypertension in DIS rats (Clin Exp Hypertens, in press). In this study, we evaluated whether clonidine inhibit the development of hypertension and clarified the effect of clonidine on alpha1-, and alpha2 adrenoceptors in renal basolateral mambranes in DIS rats.Methods : Four week-old Dahl-Iwai salt sensitive rats were divided into three groups and fed a high-salt(8.0%NaCl) until 8weeks of age. G1 : control group drunk only distillled water, G2 : clonidine group drunk only 0.4mg/L clonidine solution, G3 : withdrawal group drunk only the clonidine solution for the first 2 weeks and only distillled water for the later 2 weeks. At 8weeks … More of age, urine was collected, then renal basolateral membranes were obtained using Percoll density. Alpha1- and alpha2- adrenoceptor density were assayd using 3H-prazosin and 3H-rauwolscine. Systolic blood pressure (SBP) was measured by tail-cuff method. Urine catecholamines are assayd by HPLC.Results : At 6 weeks of age, SBPs were higher in G1 (160<plus-minus>0.8, mean<plus-minus>SEM) than G2 (144<plus-minus>0.7) and G3 (145<plus-minus>0.9). SBPs of G3 after withdrawal of clonidine rose into the same SBP levels of G1 at 8 weeks of age (G1 : 229<plus-minus>3.6, G3 : 227<plus-minus>3.6), while SBPs of G2 (198<plus-minus>0.6) were kept lower than those of G1 and G3. Urinary noradrenaline (NA) was higher in G3 (639<plus-minus>37ng/day) than G1 (441<plus-minus>38) and G2 (236<plus-minus>20). Urinary adrenaline (AD) was higher in G3 (152<plus-minus>19ng/day) than G2 (76<plus-minus>9). Both alpha1- and alpha2-adrenoceptor densities were lower in G3 (alpha1 239<plus-minus>4, alpha2 504<plus-minus>26 fmol/mg protein) than G1 (373<plus-minus>39,737<plus-minus>54) and G2(3Conclusions : (1) Clonidine treatment failed to suppress the development of hypertension in DIS.(2) Discontinuation of clonidine increased urinary catecholamine and decreased alpha1- and alpha2- adrenoceptor densities in renal basolateral membranes of DIS rats. Less