|Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1992 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1991 : ¥1,200,000 (Direct Cost : ¥1,200,000)
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
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.