Central and renal alpha-adrenergic receptor with the development of salt-induced hypertension in Dahl-Iwai salt-sensitive rats.

本文报道了喂食低盐饮食的自发性高血压大鼠肾基底膜α2-肾上腺素能受体和α-和α2-肾上腺素能受体的改变(高血压杂志9：901-908,1991，琉球医学杂志12：62-73,1991)。在本研究中，我们观察了盐敏感性大鼠(S)脑、肾α-肾上腺素能受体的数量和亲和力与高血压的关系。为了进一步探讨延髓内的α-肾上腺素能受体是否参与盐敏感性大鼠的高血压发病机制，我们通过测量血压和脉搏，研究了心血管中枢微量注射α-受体激动剂和α-拮抗剂的作用。受体结合研究：DAHL-Iwai S大鼠从4周龄开始分别饲喂高盐(8.0%)和低盐(0.3%)饲料2周或6周。在6周龄或10周龄时，我们测量了钠平衡，并对α和α…进行了量化放射配基结合分析显示脑和肾小管基底膜上有更多的α2-肾上腺素能受体。6周龄时，高盐组大鼠延髓α2受体密度低于低盐组，肾基底膜α2受体密度高于低盐组。两组之间的差异在10周龄时消失。与10周龄(+0.02mEq/d/g体重)相比，高盐组大鼠在6周龄(+0.06mEq/d/g体重)表现出更多的正钠平衡。高盐摄入可能通过减少延髓的α2受体，增加肾小管基底膜的α2受体和α2受体，导致交感神经活动增强和钠滞留。这些机制可能参与了Dahl-Iwai盐敏感大鼠高血压的形成。显微注射实验：Dahl-Iwai大鼠从6周龄开始以高盐(8.0%)或低盐(0.3%)饲料喂养10-14天，并用乌拉坦麻醉。延髓头端腹外侧区微量注射α2受体激动剂可乐定可降低高盐和低盐饮食大鼠的血压和脉率。注射α2拮抗剂SK&F86466不改变血压和脉搏频率。相反，向延髓尾侧腹外侧区(CVLM)注射可乐定可引起持续性的血压升高，有时会伴随一过性的血压下降。向CVLm内注射SK&F86466具有降压作用。因此，涉及α2-肾上腺素能受体的内在机制强直地抑制了CVLM中的局部心血管神经元。较少

We reported altered alpha2-adrenoceptors in renal basolateral membrane and alphal-and alpha2 adrenoceptors in spontaneously hypertensive rats fed a low salt diet(J Hypertension 9 : 901-908, 1991, Ryukyu Medical J 12 : 62-73, 1991). In this study, we evaluated the number and affinity of alpha-adrenoceptors of brain and kidney with the development of hypertension in Dahl-Iwai salt-sensitive (Dahl-Iwai S) rats which are an experimental animal model of salt-induced hypertension. And in order to investigate extensively whether alpha-adrenoceptors in medulla oblongata were involved in salt-induced hypertension of Dahl-Iwai salt-sensitive rat, we studied effect of microinjection of alpha-agonist and alpha-antagonist into the cardiovascular center by measuring blood pressure and pulse.Receptor binding study : Dahl-Iwai S rats were fed on high(8.0%)- or low(0.3%)-salt diet for 2 or 6 weeks from 4 weeks of age. At the age of 6 or 10 weeks, we measured sodium balance and quantified alphal- and al … More pha2-adrenergic receptors of brain and renal tubular basolateral membranes by radioligand binding assay. At the age of 6 weeks, alpha2-receptor densities in medulla oblongata was lower and alphal- and alpha2-receptors densities on the renal basolateral membrane were higher in the high-salt group than in the low salt group. The difference between the groups disappeared at the age of 10 weeks. Rats fed on high-salt group showed more positive sodium balance at the age of 6 weeks (+0.06mEq/day/g body weight) compared to the age of 10 weeks (+0.02mEq/day/g body weight). Through a decrease in the alpha2-receptor in the medulla oblongata and an increase in alphal-and alpha2 receptors in the renal tubular basolateral membrane, high salt intake may result in enhancement of the sympathetic nerve activity and sodium retention. These mechanisms may contribute to the development of hypertension in Dahl-Iwai salt-sensitive rats.Experiment of microinjection : Dahl-Iwai rats were fed on high(8.0%)- or low(0.3%)-salt diet for 10-14 days from 6weeks of age, and anesthetized with urethane. Microinjection of clonidine (alpha2- agonist) into the rostral ventro lateral medulla (RVLM) decreased blood pressure(BP) and pulse rate in Dahl S and R rats either on low- and high-salt diet. Injection of SK&F86466 (alpha2-antagonist), however, did not change BP and pulse rate. In contrast, injection of clonidine into the caudal ventrolateral medulla (CVLM) caused a persistant BP elevation which was sometimes followed by a transient fall in BP. And injection of SK&F86466 into CVLM caused a depressor effect. Thus, intrinsic mechanisms involving in alpha2-adrenoceptor tonically inhibited the local cardiovascular neuron in CVLM. Less