|Budget Amount *help
¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1994 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1993 : ¥1,200,000 (Direct Cost : ¥1,200,000)
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
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(3
Conclusions : (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.