Upregulation of renin-angiotensin system and downregulation of kallikrein in obstructive nephropathy
S. S. el-Dahr, J. Gee, S. Dipp, B. G. Hanss, R. C. Vari and J. Chao Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana 70112. The purpose of this study was to delineate the effects of prolonged (1 and 5 wk) unilateral ureteral obstruction (UUO) on the intrarenal r...
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| Veröffentlicht in: | American journal of physiology. Renal, fluid and electrolyte physiology fluid and electrolyte physiology, 1993-05, Vol.264 (5), p.874-F881 |
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| container_title | American journal of physiology. Renal, fluid and electrolyte physiology |
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| creator | el-Dahr, S. S Gee, J Dipp, S Hanss, B. G Vari, R. C Chao, J |
| description | S. S. el-Dahr, J. Gee, S. Dipp, B. G. Hanss, R. C. Vari and J. Chao
Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana 70112.
The purpose of this study was to delineate the effects of prolonged (1 and
5 wk) unilateral ureteral obstruction (UUO) on the intrarenal
renin-angiotensin and kallikrein-kinin systems in the rat. Systolic blood
pressure (SBP) and plasma angiotensin (ANG) II levels were significantly
higher at 1 and 5 wk of obstruction than in sham-operated groups. Also,
plasma renin activity and ANG I levels were elevated at 1 wk (P < 0.05),
and plasma angiotensin-converting enzyme (ACE)-kininase II activity was
elevated at 5 wk (P < 0.05). Blockade of ANG II receptors with losartan
(Dup 753) prevented the rise in SBP after UUO and normalized SBP in
chronically hypertensive UUO rats. Renin mRNA levels and ANG II content
were elevated in the obstructed kidneys at 1 and 5 wk compared with
sham-operated kidneys (P < 0.05). ACE-kininase II activity was elevated
in both the obstructed and contralateral kidneys at 5 wk compared with
sham-operated kidneys (P < 0.05). In marked contrast to renin, total
immunoreactive kallikrein contents and tissue kallikrein mRNA levels in the
obstructed kidneys were reduced to 25% of sham-operated kidneys both at 1
and 5 wk (P < 0.001). The results indicate that urinary obstruction
activates renin and suppresses kallikrein gene expression. Activation of
ACE-kininase II by UUO also serves to enhance intrarenal ANG II generation
and kinin degradation. The results implicate ANG II overproduction and
kinin deficiency in the pathogenesis of UUO-induced hypertension and
intrarenal vasoconstriction. |
| format | Article |
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Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana 70112.
The purpose of this study was to delineate the effects of prolonged (1 and
5 wk) unilateral ureteral obstruction (UUO) on the intrarenal
renin-angiotensin and kallikrein-kinin systems in the rat. Systolic blood
pressure (SBP) and plasma angiotensin (ANG) II levels were significantly
higher at 1 and 5 wk of obstruction than in sham-operated groups. Also,
plasma renin activity and ANG I levels were elevated at 1 wk (P < 0.05),
and plasma angiotensin-converting enzyme (ACE)-kininase II activity was
elevated at 5 wk (P < 0.05). Blockade of ANG II receptors with losartan
(Dup 753) prevented the rise in SBP after UUO and normalized SBP in
chronically hypertensive UUO rats. Renin mRNA levels and ANG II content
were elevated in the obstructed kidneys at 1 and 5 wk compared with
sham-operated kidneys (P < 0.05). ACE-kininase II activity was elevated
in both the obstructed and contralateral kidneys at 5 wk compared with
sham-operated kidneys (P < 0.05). In marked contrast to renin, total
immunoreactive kallikrein contents and tissue kallikrein mRNA levels in the
obstructed kidneys were reduced to 25% of sham-operated kidneys both at 1
and 5 wk (P < 0.001). The results indicate that urinary obstruction
activates renin and suppresses kallikrein gene expression. Activation of
ACE-kininase II by UUO also serves to enhance intrarenal ANG II generation
and kinin degradation. The results implicate ANG II overproduction and
kinin deficiency in the pathogenesis of UUO-induced hypertension and
intrarenal vasoconstriction.</description><identifier>ISSN: 0363-6127</identifier><identifier>ISSN: 0002-9513</identifier><identifier>EISSN: 2161-1157</identifier><identifier>PMID: 8498541</identifier><language>eng</language><publisher>United States</publisher><subject>Angiotensin II - antagonists & inhibitors ; Angiotensin II - blood ; Angiotensin II - metabolism ; Animals ; Biphenyl Compounds - pharmacology ; Blood Pressure - drug effects ; Gene Expression ; Imidazoles - pharmacology ; Kallikreins - genetics ; Kallikreins - metabolism ; Kidney - metabolism ; Kidney Diseases - etiology ; Kidney Diseases - metabolism ; Losartan ; Male ; Rats ; Rats, Sprague-Dawley ; Renin-Angiotensin System - genetics ; RNA, Messenger - metabolism ; Tetrazoles - pharmacology ; Ureteral Obstruction - complications ; Ureteral Obstruction - metabolism</subject><ispartof>American journal of physiology. Renal, fluid and electrolyte physiology, 1993-05, Vol.264 (5), p.874-F881</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8498541$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>el-Dahr, S. S</creatorcontrib><creatorcontrib>Gee, J</creatorcontrib><creatorcontrib>Dipp, S</creatorcontrib><creatorcontrib>Hanss, B. G</creatorcontrib><creatorcontrib>Vari, R. C</creatorcontrib><creatorcontrib>Chao, J</creatorcontrib><title>Upregulation of renin-angiotensin system and downregulation of kallikrein in obstructive nephropathy</title><title>American journal of physiology. Renal, fluid and electrolyte physiology</title><addtitle>Am J Physiol</addtitle><description>S. S. el-Dahr, J. Gee, S. Dipp, B. G. Hanss, R. C. Vari and J. Chao
Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana 70112.
The purpose of this study was to delineate the effects of prolonged (1 and
5 wk) unilateral ureteral obstruction (UUO) on the intrarenal
renin-angiotensin and kallikrein-kinin systems in the rat. Systolic blood
pressure (SBP) and plasma angiotensin (ANG) II levels were significantly
higher at 1 and 5 wk of obstruction than in sham-operated groups. Also,
plasma renin activity and ANG I levels were elevated at 1 wk (P < 0.05),
and plasma angiotensin-converting enzyme (ACE)-kininase II activity was
elevated at 5 wk (P < 0.05). Blockade of ANG II receptors with losartan
(Dup 753) prevented the rise in SBP after UUO and normalized SBP in
chronically hypertensive UUO rats. Renin mRNA levels and ANG II content
were elevated in the obstructed kidneys at 1 and 5 wk compared with
sham-operated kidneys (P < 0.05). ACE-kininase II activity was elevated
in both the obstructed and contralateral kidneys at 5 wk compared with
sham-operated kidneys (P < 0.05). In marked contrast to renin, total
immunoreactive kallikrein contents and tissue kallikrein mRNA levels in the
obstructed kidneys were reduced to 25% of sham-operated kidneys both at 1
and 5 wk (P < 0.001). The results indicate that urinary obstruction
activates renin and suppresses kallikrein gene expression. Activation of
ACE-kininase II by UUO also serves to enhance intrarenal ANG II generation
and kinin degradation. The results implicate ANG II overproduction and
kinin deficiency in the pathogenesis of UUO-induced hypertension and
intrarenal vasoconstriction.</description><subject>Angiotensin II - antagonists & inhibitors</subject><subject>Angiotensin II - blood</subject><subject>Angiotensin II - metabolism</subject><subject>Animals</subject><subject>Biphenyl Compounds - pharmacology</subject><subject>Blood Pressure - drug effects</subject><subject>Gene Expression</subject><subject>Imidazoles - pharmacology</subject><subject>Kallikreins - genetics</subject><subject>Kallikreins - metabolism</subject><subject>Kidney - metabolism</subject><subject>Kidney Diseases - etiology</subject><subject>Kidney Diseases - metabolism</subject><subject>Losartan</subject><subject>Male</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Renin-Angiotensin System - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Tetrazoles - pharmacology</subject><subject>Ureteral Obstruction - complications</subject><subject>Ureteral Obstruction - metabolism</subject><issn>0363-6127</issn><issn>0002-9513</issn><issn>2161-1157</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkM9LwzAAhYMoc07_BKEnb5UmaX70KMOpMPDiziFN0zZbmtQkdfS_d7hdhAfv8D7e4bsCSwQpzCEk7BosC0xxTiFit-Auxn1RIEQ5XYAFLytOSrgEzW4MupusTMa7zLdZ0M64XLrO-KRdNC6Lc0x6yKRrssYf3X_8IK01h6BP3Cm-jilMKpkfnTk99sGPMvXzPbhppY364dIrsNu8fq3f8-3n28f6ZZv3kBYpL2Fds6oqCZac1BXkXGHVlgwSqRBUBDNIecsJUrxQCsuWMi5lSRRFpOCU4RV4Ov-OwX9POiYxmKi0tdJpP0XBCCOw-AMfL-BUD7oRYzCDDLO4aDntz-e9N11_NEGLsZ-j8dZ3s5D7kzInrUC0FERsOCvxLzANccg</recordid><startdate>199305</startdate><enddate>199305</enddate><creator>el-Dahr, S. S</creator><creator>Gee, J</creator><creator>Dipp, S</creator><creator>Hanss, B. G</creator><creator>Vari, R. C</creator><creator>Chao, J</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>199305</creationdate><title>Upregulation of renin-angiotensin system and downregulation of kallikrein in obstructive nephropathy</title><author>el-Dahr, S. S ; Gee, J ; Dipp, S ; Hanss, B. G ; Vari, R. C ; Chao, J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h160t-41bb799453a85b9188c3cf4715ac21c537168f852c80cc3af678aa45c62508673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Angiotensin II - antagonists & inhibitors</topic><topic>Angiotensin II - blood</topic><topic>Angiotensin II - metabolism</topic><topic>Animals</topic><topic>Biphenyl Compounds - pharmacology</topic><topic>Blood Pressure - drug effects</topic><topic>Gene Expression</topic><topic>Imidazoles - pharmacology</topic><topic>Kallikreins - genetics</topic><topic>Kallikreins - metabolism</topic><topic>Kidney - metabolism</topic><topic>Kidney Diseases - etiology</topic><topic>Kidney Diseases - metabolism</topic><topic>Losartan</topic><topic>Male</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Renin-Angiotensin System - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Tetrazoles - pharmacology</topic><topic>Ureteral Obstruction - complications</topic><topic>Ureteral Obstruction - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>el-Dahr, S. S</creatorcontrib><creatorcontrib>Gee, J</creatorcontrib><creatorcontrib>Dipp, S</creatorcontrib><creatorcontrib>Hanss, B. G</creatorcontrib><creatorcontrib>Vari, R. C</creatorcontrib><creatorcontrib>Chao, J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of physiology. Renal, fluid and electrolyte physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>el-Dahr, S. S</au><au>Gee, J</au><au>Dipp, S</au><au>Hanss, B. G</au><au>Vari, R. C</au><au>Chao, J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Upregulation of renin-angiotensin system and downregulation of kallikrein in obstructive nephropathy</atitle><jtitle>American journal of physiology. Renal, fluid and electrolyte physiology</jtitle><addtitle>Am J Physiol</addtitle><date>1993-05</date><risdate>1993</risdate><volume>264</volume><issue>5</issue><spage>874</spage><epage>F881</epage><pages>874-F881</pages><issn>0363-6127</issn><issn>0002-9513</issn><eissn>2161-1157</eissn><abstract>S. S. el-Dahr, J. Gee, S. Dipp, B. G. Hanss, R. C. Vari and J. Chao
Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana 70112.
The purpose of this study was to delineate the effects of prolonged (1 and
5 wk) unilateral ureteral obstruction (UUO) on the intrarenal
renin-angiotensin and kallikrein-kinin systems in the rat. Systolic blood
pressure (SBP) and plasma angiotensin (ANG) II levels were significantly
higher at 1 and 5 wk of obstruction than in sham-operated groups. Also,
plasma renin activity and ANG I levels were elevated at 1 wk (P < 0.05),
and plasma angiotensin-converting enzyme (ACE)-kininase II activity was
elevated at 5 wk (P < 0.05). Blockade of ANG II receptors with losartan
(Dup 753) prevented the rise in SBP after UUO and normalized SBP in
chronically hypertensive UUO rats. Renin mRNA levels and ANG II content
were elevated in the obstructed kidneys at 1 and 5 wk compared with
sham-operated kidneys (P < 0.05). ACE-kininase II activity was elevated
in both the obstructed and contralateral kidneys at 5 wk compared with
sham-operated kidneys (P < 0.05). In marked contrast to renin, total
immunoreactive kallikrein contents and tissue kallikrein mRNA levels in the
obstructed kidneys were reduced to 25% of sham-operated kidneys both at 1
and 5 wk (P < 0.001). The results indicate that urinary obstruction
activates renin and suppresses kallikrein gene expression. Activation of
ACE-kininase II by UUO also serves to enhance intrarenal ANG II generation
and kinin degradation. The results implicate ANG II overproduction and
kinin deficiency in the pathogenesis of UUO-induced hypertension and
intrarenal vasoconstriction.</abstract><cop>United States</cop><pmid>8498541</pmid></addata></record> |
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| ispartof | American journal of physiology. Renal, fluid and electrolyte physiology, 1993-05, Vol.264 (5), p.874-F881 |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Angiotensin II - antagonists & inhibitors Angiotensin II - blood Angiotensin II - metabolism Animals Biphenyl Compounds - pharmacology Blood Pressure - drug effects Gene Expression Imidazoles - pharmacology Kallikreins - genetics Kallikreins - metabolism Kidney - metabolism Kidney Diseases - etiology Kidney Diseases - metabolism Losartan Male Rats Rats, Sprague-Dawley Renin-Angiotensin System - genetics RNA, Messenger - metabolism Tetrazoles - pharmacology Ureteral Obstruction - complications Ureteral Obstruction - metabolism |
| title | Upregulation of renin-angiotensin system and downregulation of kallikrein in obstructive nephropathy |
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