Document Detail


Plasmin in urine from patients with type 2 diabetes and treatment-resistant hypertension activates ENaC in vitro.
MedLine Citation:
PMID:  24805959     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND:: Aberrant filtration of plasminogen from plasma and subsequent activation to plasmin in the urinary space may activate proteolytically the epithelial sodium channel, ENaC. In conditions with chronic albuminuria, this may cause hypertension. It was hypothesized that patients with type 2 diabetes mellitus (T2DM) and treatment-resistant hypertension excrete plasmin(ogen) in urine in proportion to albumin and that plasmin confers to urine the ability to activate ENaC.
METHOD:: Patients (n = 113) with T2DM and resistant hypertension, defined as systolic blood pressure (SBP) more than 130 mmHg and/or diastolic blood pressure (DBP) more than 80 mmHg despite use of at least three drugs with one diuretic and one renin-angiotensin system inhibitor, were included. Urine was analyzed for albumin, creatinine, plasmin(ogen), protease activity, and ability to activate inward current in single collecting duct cells.
RESULTS:: Mean ambulatory SBP/DBP was 143 ± 1/77 ± 0.7 mmHg; HbA1c 7.35%; and eGFR 81.0 ml/min per 1.73 m (geometric means). Patients with microalbuminuria (39%) and macroalbuminuria (13%) displayed significantly elevated levels of urinary plasmin(ogen) normalized to urine creatinine compared with patients with normal excretion of albumin (48%). Urinary plasminogen correlated significantly to urine albumin. Western immunoblotting and gelatine zymography confirmed active plasmin in urine samples from patients with microalbuminuria and macroalbuminuria. Single collecting duct cells displayed significantly increased, amiloride-sensitive, inward current when superfused with urine from albuminuric patients compared with patients with normal albumin excretion. Urinary plasminogen/creatinine ratio correlated significantly with 24-h ambulatory blood pressure.
CONCLUSION:: Aberrant presence of plasmin in preurine may inappropriately activate ENaC in patients with type 2 diabetes and microalbuminuria. This may contribute to treatment-resistant hypertension.
Authors:
Kristian B Buhl; Christina S Oxlund; Ulla G Friis; Per Svenningsen; Claus Bistrup; Ib A Jacobsen; Boye L Jensen
Related Documents :
9402929 - The age-associated alterations in late diastolic function in mice are improved by calor...
10714529 - Short-term effects of ecadotril in dogs with induced congestive heart failure.
21462839 - Clinical aspects of hypertension in children.
11983539 - Assessment of synchrony relationships between the native left ventricle and the heartma...
10619589 - Reduction in arterial distensibility in hypertensive patients as evaluated by ambulator...
10567179 - Effects of transdermal 17beta-estradiol on left ventricular anatomy and performance in ...
17670199 - Transgenic and transmural revascularization: regional myocardial tissue pressure during...
7944819 - Pericardium-lined skeletal muscle ventricles in circulation up to 589 days.
2044099 - Hypertensive renal damage.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-5-6
Journal Detail:
Title:  Journal of hypertension     Volume:  -     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-5-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Oxidized low-density lipoprotein in postmenopausal women.
Next Document:  Oxygen vacancy clustering and pseudogap behaviour at the LaAlO3/SrTiO3 interface.