Regression of hypertension : molecular analysis and epigenetic assessment

• Project/Area Number: 20590984
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Keio University
• Principal Investigator: SASAMURA Hiroyuki Keio University, 医学部, 准教授 (00235293)
• Co-Investigator(Kenkyū-buntansha): ITOH Hiroshi 慶應義塾大学, 医学部, 教授 (40252457)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 高血圧 / 退行 / レニンーアンジオテンシン系 / 糸球体硬化

Research Abstract

Hypertension is the most prevalent disease in Japan, and affects at least one in four of the general population. Although hypertension is considered to be a progressive, irreversible disease, we demonstrated in this study that reversal or regression of hypertension may be feasible in animal models of hypertension. Regression of hypertension was achieved by 'pulse' treatment with an angiotensin receptor blocker at 10-50 times the normal dose, by a mechanism involving reversal of renal arteriolar hypertrophy.

Research Products

• [Journal Article] Regression of glomerulosclerosis in response to transient treatment with angiotensin II blockers is attenuated by blockade of matrix metalloproteinase-2. (2010)
  • Author(s): K.Hayashi, H.Sasamura, K.Ishiguro, Y.Sakamaki, T.Azegami, H.Itoh
  • Journal Title: Kidney International 78 Pages: 69-78
  • Peer Reviewed
• [Journal Article] Absence of gelatinase (MMP-9) or collagenase (MMP-13) attenuates adriamycin-induced albuminuria and glomerulosclerosis. (2010)
  • Author(s): Y.Sakamaki, H.Sasamura, K.Hayashi, K.Ishiguro, H.Takaishi, H.Okada, J.M.D'Armiento, T.Saruta, H.Itoh
  • Journal Title: Nephron 115
  • Peer Reviewed
• [Journal Article] Regression of glomerulosclerosis in response to transient treatment with angiotensin II blockers is attenuated by blockade of matrix metalloproteinase-2. (2010)
  • Author(s): K.Hayashi, H.Sasamura, et al.
  • Journal Title: Kidney International Volume: 78 Pages: 69-78
  • Peer Reviewed
• [Journal Article] Absence of gelatinase (MMP-9) or collagenase (MMP-13) attenuates adriamycin-induced albuminuria and glomerulosclerosis. (2010)
  • Author(s): Y.Sakamaki, H.Sasamura, et al.
  • Journal Title: Nephron Volume: 115 Pages: 22-32
  • Peer Reviewed
• [Journal Article] Pulse treatment with high-dose angiotensin blocker reverses renal arteriolar hypertrophy and regresses hypertension. (2009)
  • Author(s): K.Ishiguro, K.Hayashi, H.Sasamura, Y.Sakamaki, H.Itoh
  • Journal Title: Hypertension 53 Pages: 83-89
  • Peer Reviewed
• [Journal Article] Prevention and regression of hypertension: role of renal microvascular protection. (2009)
  • Author(s): H.Sasamura, K.Hayashi, K.Ishiguro, H.Nakaya, T.Saruta, H.Itoh
  • Journal Title: Hypertension Research 32 Pages: 658-664
  • NAID: 10025164652
  • Peer Reviewed
• [Journal Article] 'Pulse' treatment with high-dose angiotensin blocker reverses renal arteriolar hypertrophy and regresses hypertension (2009)
  • Author(s): K.Ishiguro, H.Sasamura, et al.
  • Journal Title: Hypertension 53 Pages: 83-89
  • Peer Reviewed
• [Journal Article] Prevention and regression of hypertension : role of renal microvascular protection (2009)
  • Author(s): H.Sasamura, K.Hayashi, et al.
  • Journal Title: Hypertension Research 32 Pages: 658-664
  • NAID: 10025164652
  • Peer Reviewed
• [Journal Article] Differential effects of transient treatment of spontaneously hypertensive rats with various antihypertensive agents on the subsequent development of diabetic nephropathy. (2008)
  • Author(s): K.Ishiguro, H.Sasamura, Y.Sakamaki, K.Hayashi, H.Itoh
  • Journal Title: Nephron 109 Pages: 20-28
  • Peer Reviewed
• [Journal Article] Short treatment with the angiotensin receptor blocker candesartan surveyed by telemedicine (STAR CAST) study : rationale and study design. (2008)
  • Author(s): H.Sasamura, H.Nakaya, T.Takebayashi, Y.Sato, K.Ishiguro, M.Ryuzaki, M.Murakami, S.Julius, H.Itoh
  • Journal Title: Hypertension Research 31 Pages: 1843-1849
  • NAID: 10024827357
  • Peer Reviewed
• [Journal Article] Differential effects of transient treatment of spontaneously hyperten sive rats with various antihypertensive agents on the subsequent de velopment of diabetic nephropathy (2008)
  • Author(s): K. Ishiguro, H, Sasamura, et al.
  • Journal Title: Nephron 109 Pages: 20-28
  • Peer Reviewed
• [Journal Article] Short treatment with the angiotensin receptor blocker candesartan surveyed by telemedicine (STAR CAST) study : rationale and studydesign (2008)
  • Author(s): H. Sasamura, H. Nakaya, et al.
  • Journal Title: Hypertension Research 31 Pages: 1843-1849
  • Peer Reviewed
• [Presentation] Transient treatment with high-dose angiotensin receptor blocker (ARB) causes regression of hypertension in a rat model of metabolic syndrome (SHRmcr-cp). (2010)
  • Author(s): K.Ishiguro, H.Sasamura, et al.
  • Organizer: 23rd International Society of Hypertension
  • Place of Presentation: Vancouver
  • Year and Date: 2010-09-28
• [Presentation] Short-term treatment with high-dose angiotensin blocker (ARB) induces sustained regression of adriamycin-induced glomerulosclerosis and albuminuria. (2010)
  • Author(s): K.Hayashi, H.Sasamura, et al.
  • Organizer: 23rd International Society of Hypertension
  • Place of Presentation: Vancouver
  • Year and Date: 2010-09-28
• [Presentation] The short treatment with the angiotensin receptor blocker candesartan surveyed by telemedicine (STAR CAST) study : design and preliminary report. (2010)
  • Author(s): H.Sasamura, H.Nakaya, S.Julius, Y.Sato, H.Itoh
  • Organizer: 23^<rd> Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Vancouver
  • Year and Date: 2010-09-26
• [Presentation] Transient treatment with high-dose angiotensin receptor blocker (ARB) causes regression of hypertension in a rat model of metabolic syndrome (SHRmcr-cp). (2010)
  • Author(s): K.Ishiguro, H.Sasamura, Y.Sakamaki, K.Hayashi, T Azegami, H.Itoh
  • Organizer: 23^<rd> Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Vancouver
  • Year and Date: 2010-09-26
• [Presentation] Prevention of hypertension and renal injury by a renin-angiotensin system (RAS) vaccine in L-NAME-treated spontaneously hypertensive rats (SHR). (2010)
  • Author(s): T.Azegami, H.Sasamura, K.Hayashi, K.Ishiguro, H.Itoh
  • Organizer: 23^<rd> Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Vancouver
  • Year and Date: 2010-09-26
• [Presentation] Short-term treatment with high-dose angiotensin blocker (ARB) induces sustained regression of adriamycin-induced glomerulosclerosis and albuminuria. (2010)
  • Author(s): K.Hayashi, H.Sasamura, K.Ishiguro, Y.Sakamaki, T.Azegami, H.Itoh
  • Organizer: 23^<rd> Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Vancouver
  • Year and Date: 2010-09-26
• [Presentation] Assessment of potential risk factors for cardiovascular disease in patients with chronic kidney disease (CKD) by metabolome analysis. (2010)
  • Author(s): K.Hayashi, H.Sasamura, T.Hishiki, M.Suematsu, S.Ikeda, T.Soga, H.Itoh
  • Organizer: 23^<rd> Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Vancouver
  • Year and Date: 2010-09-26
• [Presentation] Efficacy of renin-angiotensin system (RAS) vaccine for prevention of proteinuria and renal injury in spontaneously hypertensive rats (SHR). (2010)
  • Author(s): T.Azegami, H.Sasamura, K.Hayashi, K.Ishiguro, H.Itoh
  • Organizer: 6^<th> International Congress of Pathophysiology
  • Place of Presentation: Montreal
  • Year and Date: 2010-09-22
• [Presentation] Role of extracellular matrix (ECM) remodeling in high-dose angiotensin blocker-induced regression of hypertension and glomerulosclerosis. (2010)
  • Author(s): K.Hayashi, H.Sasamura, K.Ishiguro, Y.Sakamaki, T.Azegami, H.Itoh
  • Organizer: 6^<th> International Congress of Pathophysiology
  • Place of Presentation: Montreal
  • Year and Date: 2010-09-22
• [Presentation] The short treatment with the angiotensin receptor blocker candesartan surveyed by telemedicine (STAR CAST) study : rationale and interim report. (2010)
  • Author(s): H.Sasamura, H.Nakaya, S.Julius, Y.Sato, H.Itoh
  • Organizer: 20^<th> European Meeting of Hypertension
  • Place of Presentation: Oslo
  • Year and Date: 2010-06-18
• [Presentation] Prevention of proteinuria and renal injury by a renin-angiotensin system (RAS) vaccine in spontaneously hypertensive rats (SHR). (2010)
  • Author(s): T.Azegami, H.Sasamura, K.Hayashi, K.Ishiguro, H.Itoh
  • Organizer: International Society of Nephrology Nexus Symposium
  • Place of Presentation: Kyoto
  • Year and Date: 2010-04-15
• [Presentation] Treatment with high-dose angiotensin blocker regresses adriamycin-induced glomerulosclerosis and albuminuria. (2010)
  • Author(s): K.Hayashi, H.Sasamura, K.Ishiguro, Y.Sakamaki, T.Azegami, H.Itoh
  • Organizer: International Society of Nephrology Nexus Symposium
  • Place of Presentation: Kyoto
  • Year and Date: 2010-04-15
• [Presentation] Metabolomic profiling as a tool for the assessment of patients with chronic kidney disease. (2010)
  • Author(s): K.Hayashi, H.Sasamura, T.Hishiki, M.Suematsu, S.Ikeda, T.Soga, H.Itoh
  • Organizer: International Society of Nephrology Nexus Symposium
  • Place of Presentation: Kyoto
  • Year and Date: 2010-04-15
• [Presentation] Microarray analysis of mechanisms involved in the prevention and regression of hypertension by angiotensin receptor blocker (ARB) in spontaneously hypertensive rats. (2010)
  • Author(s): H.Sasamura, K.Hayashi, K.Ishiguro, Y.Sakamaki, T.Azegami, H.Itoh
  • Organizer: 14^<th> International Congress of Endocrinology
  • Place of Presentation: Kyoto
  • Year and Date: 2010-03-26
• [Presentation] 'Pulse' treatment with high-dose angiotensin receptor blocker (ARB) causes regression of hypertension in SHRmcr-cp rats with metabolic syndrome. (2010)
  • Author(s): K.Ishiguro, H.Sasamura, Y.Sakamaki, K.Hayashi, H.Itoh
  • Organizer: 14^<th> International Congress of Endocrinology
  • Place of Presentation: Kyoto
  • Year and Date: 2010-03-26
• [Presentation] メタボリックシンドローム(MetS)モデル動物に対する「ARB高用量パルス投与」の効果の検討 (2009)
  • Author(s): 石黒喜美子、篠村裕之, 他
  • Organizer: 第32回日本高血圧学会総会
  • Place of Presentation: 大津
  • Year and Date: 2009-10-01
• [Presentation] ARB高用量一過性投与は高血圧モデル動物において高血圧の退行(regression)と心血管肥大の抑制をもたらず (2009)
  • Author(s): 石黒喜美子、篠村裕之, 他
  • Organizer: 第45回高血圧関連疾患モデル学会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-05
• [Presentation] Transient prepubertal exposure to an ARB or aldosterone antagonist suppresses the subsequent development of diabetic nephropathy (2008)
  • Author(s): K. Ishiguro, H. Sasamura, et al.
  • Organizer: 22^n International Society of Hypertension
  • Place of Presentation: Berlin
  • Year and Date: 2008-06-21
• [Presentation] Short treatment with the angiotensin receptor blocker candesartan surveyed by telemedicine (STAR CAST) study : rationale and study design (2008)
  • Author(s): H. Sasamura, H. Nakaya, et al.
  • Organizer: 22^n International Society of Hypertension
  • Place of Presentation: Berlin
  • Year and Date: 2008-06-21
• [Presentation] Matrix metalloproteinase-9 (MMP-9) deletion suppresses the development of glomerulosclerosis in mice by a blood pressureand oxidative stress-independent mechanism. (2008)
  • Author(s): Y.Sakamaki, H.Sasamura, K.Kshiguro, K.Hayashi, Y.Okada, T.Saruta, H.Itoh
  • Organizer: 22nd Scientific Meeting, International Society of Hypertension
  • Place of Presentation: Berlin
  • Year and Date: 2008-06-14
• [Presentation] Comparison of costs between angiotensin receptor blocker (ARB) and calcium channel blocker (CCB) in hypertensive patients with high cardiovascular risks and analysis of the effects of new-onset diabetes, from the CASE-J Trial. (2008)
  • Author(s): H.Nakaya, H.Sasamura, Y.Sakamaki, S.Ikeda, Y.Sato, H.Itoh
  • Organizer: 22nd Scientific Meeting, International Society of Hypertension
  • Place of Presentation: Berlin
  • Year and Date: 2008-06-14
• [Presentation] Transient prepubertal exposure to an angiotensin receptor blocker or aldosterone antagonist suppresses the development of nephropathy in streptozotocin-induced diabetic hypertensive rats. (2008)
  • Author(s): K.Ishiguro, H.Sasamura, Y.Sakamaki, K.Hayashi, T.Saruta, H.Itoh
  • Organizer: 22nd Scientific Meeting, International Society of Hypertension
  • Place of Presentation: Berlin
  • Year and Date: 2008-06-14
• [Presentation] 'Pulse' treatment with high-dose angiotensin receptor blocker (ARB) causes prominent regression of established glomerulosclerotic lesions in mice. (2008)
  • Author(s): K.Hayashi, H.Sasamura, K.Ishiguro, Y.Sakamaki, H.Itoh
  • Organizer: 22nd Scientific Meeting, International Society of Hypertension
  • Place of Presentation: Berlin
  • Year and Date: 2008-06-14
• [Presentation] Microarray analysis of vascular and renal mechanisms involved in suppression of hypertension development by prehypertensive treatment in spontaneously hypertensive rats (SHR). (2008)
  • Author(s): K.Hayashi, K.Ishiguro, H.Sasamura, Y.Sakamaki, H.Itoh
  • Organizer: 22nd Scientific Meeting, International Society of Hypertension
  • Place of Presentation: Berlin
  • Year and Date: 2008-06-14
• [Presentation] Effects of 'pulse' treatment with high-dose angiotensin receptor blocker (ARB) or calcium channel blocker (CCB) on regression of hypertension and microvascular remodeling in spontaneously hypertensive rats (SHR). (2008)
  • Author(s): K.Ishiguro, K.Hayashi, H.Sasamura, Y.Sakamaki, T.Saruta, H.Itoh
  • Organizer: 22nd Scientific Meeting, International Society of Hypertension
  • Place of Presentation: Berlin
  • Year and Date: 2008-06-14
• [Presentation] Short treatment with the angiotensin receptor blocker candesartan surveyed by telemedicine (STAR CAST) study : rationale and study design. (2008)
  • Author(s): H.Sasamura, H.Nakaya, T.Takebayashi, Y.Sato, K.Ishiguro, M.Ryuzaki, M.Murakami, S.Julius, H.Itoh
  • Organizer: 22nd Scientific Meeting, International Society of Hypertension
  • Place of Presentation: Berlin
  • Year and Date: 2008-06-14