Evaluation of the role of central neurotrans mitter in animal hypertension models due to hyperactivity of the brain renin-angiotensin system.

• Project/Area Number: 10670654
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Osaka University
• Principal Investigator: MIKAMI Hiroshi School of Allied Health Sciences, Faculty of Medicine, Osaka University Department of Community Health Nursing Professor, 医学部, 教授 (80173996)
• Co-Investigator(Kenkyū-buntansha): MORIGUCHI Atsushi Osaka University, Medical School Department of Geriatric Medicine Assistant Professor, 医学系研究科, 助手 (10273666) ; RAKUGI Hiromi Osaka University, Medical School Department of Geriatric Medicine Assistant Professor, 医学系研究科, 助手 (20252679)
• Project Period (FY): 1998 – 1999
• Project Status: Completed (Fiscal Year 1999)
• Budget Amount: ¥3,800,000 (Direct Cost: ¥3,800,000); Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000); Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: Amino acid neurotransmitter / Rostral ventrolateral medulla / β-blocker / Angiotensinogen / Gene introduction / HVJ-liposome method / Oligodeoxynucleotide / Decoy / アンジオテンシンII / 神経伝達物質 / レニン.アンジオテンシン系 / 血圧調節機構 / 高血圧 / アンジオテンシンII受容体拮抗薬

Research Abstract

To evaluate the role of the central neurotransmitters in the blood pressure control by the central nervous system we conducted 2 series of experiments.
First, we evaluated the dynamics of amino acids as neurotransmitters in the ventrolateral medulla for the central blood pressure control in the rat. We measured the release of various amino acids in the rostral ventrolateral medulla (RVLM) using the brain microdialysis technique in response to intravenous β-blocker propranolol. Mean arterial pressure and the release of amino acids were monitored in response to i. v. propranolol, which decreased pressure and heart rate, and decreased the release of excitatory amino acid glutamate from RVLM. These results suggest that the reduction of the excitatory amino acid in RVLM is responsible for the hypotensive effect of propranolol.
Second, we evaluated the role of brain angiotensinogen in the spontaneously hypertensive rat (SHR) by using the HVJ-liposome method to introduce decoy oligodeoxynucleotides of angiotensinogen gene-activating factor into the brain ventrilcle to suppress angiotensinogen gene-activating elements in the promoter region of angiotensinogen gene. Blood pressure fell only in the SHR as brain angiotensinogen level decreased. These results suggest that activated generation of angiotensinogen in the brain may be involved in the generation of hypertension in SHR and also suggest that SHR may be regarded as an animal hypertension model due to hyperactivity of the brain renin-angiotensin system.

Research Products

• [Publications] Okuda N, Kohara K, Mikami H, Moriguchi A, Yamada K, Higaki J, Ogihara T: "Effect of propranolol on central neurotransmitters release in wistar rats analyzed by brain microdialysis."Clinical and Experimental Pharmacology and Physiology. 26(2). 220-224 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nishii T, Moriguchi A, Morishita R, Yamada K, Nakamura S, Tomita N, Kaneda Y, Fukamizu A, Mikami H, Higaki J, Ogihara T: "Angiotensinogen gene-activating elements regulate blood pressure in the brain."Circulation Research. 85(2). 257-263 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Okuda N.,Mikami H.et al.: "Effect of propranolol on central neurotransmitters release in wistar rats analyzed by brain dialysis"Clinical and Experimental Pharmacology and Physiology. 26(2). 220-224 (1999)
• [Publications] Nishii T.,Mikami H.et al.: "Angiotensinogen gene-activating elements regulate blood pressure in the brain"Circulation Research. 85(20). 257-263 (1999)
• [Publications] Moriguchi A et al.: "Gene therapy for cardiovascular disease:is gene therapy a real medicine in next millennium?" Proceeding of 3rd Gene Cross International Symposium. in press.
• [Publications] Moriguchi A et al.: "Activation of the brain angiotensin system by in vivo human angiotensin converting enzyme gene transfer in rats." Hypertension. in press.