The renin-angiotensin system and hypertension in autosomal recessive polycystic kidney disease.
Hypertension is a well-recognized complication of autosomal recessive polycystic kidney disease (ARPKD). The renin-angiotensin system (RAS) is a key regulator of blood pressure; however, data on the RAS in ARPKD are limited and conflicting, showing both up- and down-regulation. In the current study, we characterized intrarenal and systemic RAS activation in relationship to hypertension and progressive cystic kidney disease in the ARPKD orthologous polycystic kidney (PCK) rat. Clinical and histological measures of kidney disease, kidney RAS gene expression by quantitative real-time PCR, angiotensin II (Ang II) immunohistochemistry, and systemic Ang I and II levels were assessed in 2-, 4-, and 6-month-old cystic PCK and age-matched normal rats. PCK rats developed hypertension and progressive cystic kidney disease without significant worsening of renal function or relative kidney size. Intrarenal renin, ACE and Ang II expression was increased significantly in cystic kidneys; angiotensinogen and Ang II Type I receptor were unchanged. Systemic Ang I and II levels did not differ. This study demonstrates that intrarenal, but not systemic, RAS activation is a prominent feature of ARPKD. These findings help reconcile previous conflicting reports and suggest that intrarenal renin and ACE gene upregulation may represent a novel mechanism for hypertension development or exacerbation in ARPKD.
Goto
Miwa
M
Department of Research, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA.
Hoxha
Nita
N
Osman
Rania
R
Dell
Katherine Macrae
KM
D000375:Aging; D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009154:Mutation; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D017044:Polycystic Kidney, Autosomal Recessive / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D011956:Receptors, Cell Surface; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics; D013997:Time Factors
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; C479541:PKHD1 protein, rat; D044140:Receptor, Angiotensin, Type 1; D011956:Receptors, Cell Surface; D000808:Angiotensinogen; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D012083:Renin
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