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

• Project/Area Number: 05670625
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: University of The Ryukyus
• Principal Investigator: FUKIYAMA Koshiro University of The Ryukyus School of Medicine Professor, 医学部, 教授 (50037363)
• Project Period (FY): 1993 – 1994
• Project Status: Completed (Fiscal Year 1994)
• Budget Amount: ¥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)
• Keywords: alpha adrenergic receptor / Dahl-Iwai salt-sensitive rat / sympathetic nerve activity / kidney / clonidine treatment / Dahl-Iwai Sラット

Research Abstract

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.

Research Products

• [Publications] Tozawa M,Takishita S,Sunagawa,O,Muratani H,Imai C,Kawazoe N,Fukiyama K: "Alpha2-adrenoceptors in brain and kidney during development of hypertension in Dahl-Iwai salt-sensitive rats." Clinical and Experimental Hypertension. (in printing). (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tozawa M,Takishita S,Sunagawa O,Muratani H,Imai C,Kawazoe N,Fukiyama K18GB01 : Alpha2-adrenoceptors in brain and kidney during development of hypertension in Dahl-Iwai saltsensitive rats.19GC01 : Clin Exp Hypertens: (in press). (1995)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takishita S,Muratani H,Kawazoe N,Kimura Y,Tozawa M,Fukiyama K.: "Neural effects on renal blood flow during acute hypotension vary with antihypertensive drugs." Hypertension. 23[suppl I]. I-97-I-101 (1994)
• [Publications] Tozawa M,Imai C,Sunagawa O,Takishita S,Muratani H,Fukiyama K.: "Effects of high salt on brain stem and renal alpha2-adrenoreceptors in Dahl-Iwai salt-sensitive and-resistant rats.Proc 15th scientific meeting of the International Society of Hypertension,Melbourne,Australia,March 20-24,1994." Journal of Hypertension. 12[suppl 3]. S230- (1994)
• [Publications] Takishita S,Muratani H,Kawazoe N,Kimura Y,Tozawa M,Fukiyama K.: "Neural effects on renal blood flow during acute hypotension vary with antihypertensive drugs." Hypertension. 23〔suoolI〕. I-97-I-101 (1994)
• [Publications] Tozawa M,Imai C,Sunagawa O,Takishita S,Muratani H,Fukiyama K.: "Effects of high salt on brain stem and renal alpha2-adrenoreceptors in Dahl-Iwai salt-sensitive and-resistant rats.Proc 15th scientific meeting of the International Society of Hypertension,Melbourne,Australia,March 20-24,1994." Journal of Hypertension. 12(in printing). (1994)