Krh-594, A New Angiotensin At1 Receptor Antagonist, Ameliorates Nephropathy And Hyperlipidaemia In Diabetic Spontaneously Hypertensive Rats
SUMMARY 1. We examined whether KRH‐594, a new angiotensin AT1 receptor antagonist, ameliorates the progression of diabetic nephropathy and hyperlipidaemia in streptozotocin (STZ)‐induced diabetic unilateral nephrectomized spontaneously hypertensive rats (DM‐1K‐SHR) or not. 2. The oral administration...
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| Veröffentlicht in: | Clinical and experimental pharmacology & physiology 2000-04, Vol.27 (4), p.270-276 |
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| creator | Inada, Yoichi Murakami, Makoto Tazawa, Shigeki Akahane, Masuo |
| description | SUMMARY
1. We examined whether KRH‐594, a new angiotensin AT1 receptor antagonist, ameliorates the progression of diabetic nephropathy and hyperlipidaemia in streptozotocin (STZ)‐induced diabetic unilateral nephrectomized spontaneously hypertensive rats (DM‐1K‐SHR) or not.
2. The oral administration of KRH‐594 (3 and 10 mg/kg per day) and candesartan cilexetil (1 mg/kg per day) for 16 weeks significantly reduced systolic blood pressure, urinary albumin and urinary total protein in DM‐1K‐SHR.
3. In a histological study, KRH‐594 (3 and 10 mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose‐dependently improved glomerulosclerosis and the hyalin cast of tubules in DM‐1K‐SHR kidneys. Both KRH‐594 (10 mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose‐dependently inhibited cardiac hypertrophy.
4. KRH‐594 (3 and 10 mg/kg per day), but not candesartan cilexetil, dose‐dependently reduced the levels of triglyceride, total cholesterol and phospholipids in DM‐1K‐SHR.
5. These results suggest that KRH‐594 improves diabetic complications, such as nephropathy and hyperlipidaemia, with hypertension. |
| doi_str_mv | 10.1046/j.1440-1681.2000.03235.x |
| format | Article |
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1. We examined whether KRH‐594, a new angiotensin AT1 receptor antagonist, ameliorates the progression of diabetic nephropathy and hyperlipidaemia in streptozotocin (STZ)‐induced diabetic unilateral nephrectomized spontaneously hypertensive rats (DM‐1K‐SHR) or not.
2. The oral administration of KRH‐594 (3 and 10 mg/kg per day) and candesartan cilexetil (1 mg/kg per day) for 16 weeks significantly reduced systolic blood pressure, urinary albumin and urinary total protein in DM‐1K‐SHR.
3. In a histological study, KRH‐594 (3 and 10 mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose‐dependently improved glomerulosclerosis and the hyalin cast of tubules in DM‐1K‐SHR kidneys. Both KRH‐594 (10 mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose‐dependently inhibited cardiac hypertrophy.
4. KRH‐594 (3 and 10 mg/kg per day), but not candesartan cilexetil, dose‐dependently reduced the levels of triglyceride, total cholesterol and phospholipids in DM‐1K‐SHR.
5. These results suggest that KRH‐594 improves diabetic complications, such as nephropathy and hyperlipidaemia, with hypertension.</description><identifier>ISSN: 0305-1870</identifier><identifier>EISSN: 1440-1681</identifier><identifier>DOI: 10.1046/j.1440-1681.2000.03235.x</identifier><identifier>PMID: 10779124</identifier><language>eng</language><publisher>Melbourne, Australia: Blackwell Science Pty</publisher><subject>Albuminuria - urine ; Angiotensin Receptor Antagonists ; Animals ; AT1 receptor antagonist ; Blood Glucose - drug effects ; Blood Pressure - drug effects ; Body Weight - drug effects ; Diabetes Mellitus, Experimental - physiopathology ; Diabetes Mellitus, Experimental - prevention & control ; Diabetic Nephropathies - pathology ; Diabetic Nephropathies - physiopathology ; Diabetic Nephropathies - prevention & control ; diabetic nephropathy ; Heart - drug effects ; hyperlipidaemia ; Hyperlipidemias - blood ; Hyperlipidemias - prevention & control ; Hypertension - pathology ; Hypertension - physiopathology ; Hypertension - prevention & control ; Kidney - drug effects ; Kidney - pathology ; Kidney - physiopathology ; KRH-594 ; Lipids - blood ; Myocardium - pathology ; Nephrectomy ; Organ Size - drug effects ; Proteinuria - urine ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Receptor, Angiotensin, Type 1 ; Receptor, Angiotensin, Type 2 ; streptozotocin ; Tetrazoles - pharmacology ; Thiadiazoles - pharmacology</subject><ispartof>Clinical and experimental pharmacology & physiology, 2000-04, Vol.27 (4), p.270-276</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1440-1681.2000.03235.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1440-1681.2000.03235.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10779124$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Inada, Yoichi</creatorcontrib><creatorcontrib>Murakami, Makoto</creatorcontrib><creatorcontrib>Tazawa, Shigeki</creatorcontrib><creatorcontrib>Akahane, Masuo</creatorcontrib><title>Krh-594, A New Angiotensin At1 Receptor Antagonist, Ameliorates Nephropathy And Hyperlipidaemia In Diabetic Spontaneously Hypertensive Rats</title><title>Clinical and experimental pharmacology & physiology</title><addtitle>Clin Exp Pharmacol Physiol</addtitle><description>SUMMARY
1. We examined whether KRH‐594, a new angiotensin AT1 receptor antagonist, ameliorates the progression of diabetic nephropathy and hyperlipidaemia in streptozotocin (STZ)‐induced diabetic unilateral nephrectomized spontaneously hypertensive rats (DM‐1K‐SHR) or not.
2. The oral administration of KRH‐594 (3 and 10 mg/kg per day) and candesartan cilexetil (1 mg/kg per day) for 16 weeks significantly reduced systolic blood pressure, urinary albumin and urinary total protein in DM‐1K‐SHR.
3. In a histological study, KRH‐594 (3 and 10 mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose‐dependently improved glomerulosclerosis and the hyalin cast of tubules in DM‐1K‐SHR kidneys. Both KRH‐594 (10 mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose‐dependently inhibited cardiac hypertrophy.
4. KRH‐594 (3 and 10 mg/kg per day), but not candesartan cilexetil, dose‐dependently reduced the levels of triglyceride, total cholesterol and phospholipids in DM‐1K‐SHR.
5. These results suggest that KRH‐594 improves diabetic complications, such as nephropathy and hyperlipidaemia, with hypertension.</description><subject>Albuminuria - urine</subject><subject>Angiotensin Receptor Antagonists</subject><subject>Animals</subject><subject>AT1 receptor antagonist</subject><subject>Blood Glucose - drug effects</subject><subject>Blood Pressure - drug effects</subject><subject>Body Weight - drug effects</subject><subject>Diabetes Mellitus, Experimental - physiopathology</subject><subject>Diabetes Mellitus, Experimental - prevention & control</subject><subject>Diabetic Nephropathies - pathology</subject><subject>Diabetic Nephropathies - physiopathology</subject><subject>Diabetic Nephropathies - prevention & control</subject><subject>diabetic nephropathy</subject><subject>Heart - drug effects</subject><subject>hyperlipidaemia</subject><subject>Hyperlipidemias - blood</subject><subject>Hyperlipidemias - prevention & control</subject><subject>Hypertension - pathology</subject><subject>Hypertension - physiopathology</subject><subject>Hypertension - prevention & control</subject><subject>Kidney - drug effects</subject><subject>Kidney - pathology</subject><subject>Kidney - physiopathology</subject><subject>KRH-594</subject><subject>Lipids - blood</subject><subject>Myocardium - pathology</subject><subject>Nephrectomy</subject><subject>Organ Size - drug effects</subject><subject>Proteinuria - urine</subject><subject>Rats</subject><subject>Rats, Inbred SHR</subject><subject>Rats, Inbred WKY</subject><subject>Receptor, Angiotensin, Type 1</subject><subject>Receptor, Angiotensin, Type 2</subject><subject>streptozotocin</subject><subject>Tetrazoles - pharmacology</subject><subject>Thiadiazoles - pharmacology</subject><issn>0305-1870</issn><issn>1440-1681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkd1u1DAQhS1ERbeFV0C-4ooET2LHyQUXq6Xd_qlUBcSl5SRD10v-sL3t5hn60jhNqbgaa853xvYcQiiwGBjPPm1j4JxFkOUQJ4yxmKVJKuL9K7J4EV6TBUuZiCCX7JAcObcNoGBZ-oYcApOygIQvyOOl3USi4B_pkl7jA112d6b32DnT0aUHeosVDr63QfD6ru-M8wFtsTG91R5dMA0b2w_ab8bA1PRsHNA2ZjC1xtZoet7RL0aX6E1Fvw19mNJhv3PNOJNPV90jvdXevSUHv3Tj8N1zPSY_Tk--r86iq6_r89XyKjJJPn1I1whFVVQlFiAkryRkWFa5DIIWHMuy5hoLmUImgTMu6iQJTdS6zHUGeXpMPsxzB9v_2aHzqjWuwqaZn6YkMCGgSAP4_hnclS3WarCm1XZU_9YXgM8z8GAaHP_T1RST2qopDTWloaaY1FNMaq9WJzfTKfij2R_WivsXv7a_VSZTKdTP67W6ELBeXUpQN-lf8P2WQA</recordid><startdate>200004</startdate><enddate>200004</enddate><creator>Inada, Yoichi</creator><creator>Murakami, Makoto</creator><creator>Tazawa, Shigeki</creator><creator>Akahane, Masuo</creator><general>Blackwell Science Pty</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>200004</creationdate><title>Krh-594, A New Angiotensin At1 Receptor Antagonist, Ameliorates Nephropathy And Hyperlipidaemia In Diabetic Spontaneously Hypertensive Rats</title><author>Inada, Yoichi ; Murakami, Makoto ; Tazawa, Shigeki ; Akahane, Masuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-i2805-1ade19c9cbe91574c716ebc871ada54ebbd4ae97316714045d22ebbeaab8a6183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Albuminuria - urine</topic><topic>Angiotensin Receptor Antagonists</topic><topic>Animals</topic><topic>AT1 receptor antagonist</topic><topic>Blood Glucose - drug effects</topic><topic>Blood Pressure - drug effects</topic><topic>Body Weight - drug effects</topic><topic>Diabetes Mellitus, Experimental - physiopathology</topic><topic>Diabetes Mellitus, Experimental - prevention & control</topic><topic>Diabetic Nephropathies - pathology</topic><topic>Diabetic Nephropathies - physiopathology</topic><topic>Diabetic Nephropathies - prevention & control</topic><topic>diabetic nephropathy</topic><topic>Heart - drug effects</topic><topic>hyperlipidaemia</topic><topic>Hyperlipidemias - blood</topic><topic>Hyperlipidemias - prevention & control</topic><topic>Hypertension - pathology</topic><topic>Hypertension - physiopathology</topic><topic>Hypertension - prevention & control</topic><topic>Kidney - drug effects</topic><topic>Kidney - pathology</topic><topic>Kidney - physiopathology</topic><topic>KRH-594</topic><topic>Lipids - blood</topic><topic>Myocardium - pathology</topic><topic>Nephrectomy</topic><topic>Organ Size - drug effects</topic><topic>Proteinuria - urine</topic><topic>Rats</topic><topic>Rats, Inbred SHR</topic><topic>Rats, Inbred WKY</topic><topic>Receptor, Angiotensin, Type 1</topic><topic>Receptor, Angiotensin, Type 2</topic><topic>streptozotocin</topic><topic>Tetrazoles - pharmacology</topic><topic>Thiadiazoles - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Inada, Yoichi</creatorcontrib><creatorcontrib>Murakami, Makoto</creatorcontrib><creatorcontrib>Tazawa, Shigeki</creatorcontrib><creatorcontrib>Akahane, Masuo</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical and experimental pharmacology & physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Inada, Yoichi</au><au>Murakami, Makoto</au><au>Tazawa, Shigeki</au><au>Akahane, Masuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Krh-594, A New Angiotensin At1 Receptor Antagonist, Ameliorates Nephropathy And Hyperlipidaemia In Diabetic Spontaneously Hypertensive Rats</atitle><jtitle>Clinical and experimental pharmacology & physiology</jtitle><addtitle>Clin Exp Pharmacol Physiol</addtitle><date>2000-04</date><risdate>2000</risdate><volume>27</volume><issue>4</issue><spage>270</spage><epage>276</epage><pages>270-276</pages><issn>0305-1870</issn><eissn>1440-1681</eissn><abstract>SUMMARY
1. We examined whether KRH‐594, a new angiotensin AT1 receptor antagonist, ameliorates the progression of diabetic nephropathy and hyperlipidaemia in streptozotocin (STZ)‐induced diabetic unilateral nephrectomized spontaneously hypertensive rats (DM‐1K‐SHR) or not.
2. The oral administration of KRH‐594 (3 and 10 mg/kg per day) and candesartan cilexetil (1 mg/kg per day) for 16 weeks significantly reduced systolic blood pressure, urinary albumin and urinary total protein in DM‐1K‐SHR.
3. In a histological study, KRH‐594 (3 and 10 mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose‐dependently improved glomerulosclerosis and the hyalin cast of tubules in DM‐1K‐SHR kidneys. Both KRH‐594 (10 mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose‐dependently inhibited cardiac hypertrophy.
4. KRH‐594 (3 and 10 mg/kg per day), but not candesartan cilexetil, dose‐dependently reduced the levels of triglyceride, total cholesterol and phospholipids in DM‐1K‐SHR.
5. These results suggest that KRH‐594 improves diabetic complications, such as nephropathy and hyperlipidaemia, with hypertension.</abstract><cop>Melbourne, Australia</cop><pub>Blackwell Science Pty</pub><pmid>10779124</pmid><doi>10.1046/j.1440-1681.2000.03235.x</doi><tpages>7</tpages></addata></record> |
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| identifier | ISSN: 0305-1870 |
| ispartof | Clinical and experimental pharmacology & physiology, 2000-04, Vol.27 (4), p.270-276 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Albuminuria - urine Angiotensin Receptor Antagonists Animals AT1 receptor antagonist Blood Glucose - drug effects Blood Pressure - drug effects Body Weight - drug effects Diabetes Mellitus, Experimental - physiopathology Diabetes Mellitus, Experimental - prevention & control Diabetic Nephropathies - pathology Diabetic Nephropathies - physiopathology Diabetic Nephropathies - prevention & control diabetic nephropathy Heart - drug effects hyperlipidaemia Hyperlipidemias - blood Hyperlipidemias - prevention & control Hypertension - pathology Hypertension - physiopathology Hypertension - prevention & control Kidney - drug effects Kidney - pathology Kidney - physiopathology KRH-594 Lipids - blood Myocardium - pathology Nephrectomy Organ Size - drug effects Proteinuria - urine Rats Rats, Inbred SHR Rats, Inbred WKY Receptor, Angiotensin, Type 1 Receptor, Angiotensin, Type 2 streptozotocin Tetrazoles - pharmacology Thiadiazoles - pharmacology |
| title | Krh-594, A New Angiotensin At1 Receptor Antagonist, Ameliorates Nephropathy And Hyperlipidaemia In Diabetic Spontaneously Hypertensive Rats |
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