Plasmin in urine from patients with type 2 diabetes and treatment-resistant hypertension activates ENaC in vitro
| Autor: | Kristian B Buhl, Boye L. Jensen, Claus Bistrup, Ib Abildgaard Jacobsen, Christina Stolzenburg Oxlund, Ulla G. Friis, Per Svenningsen |
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| Rok vydání: | 2014 |
| Předmět: |
kidney
medicine.medical_specialty Ambulatory blood pressure Physiology Plasmin Urinary system medicine.medical_treatment Drug Resistance Blood Pressure Urine Excretion Internal medicine Internal Medicine Albuminuria Humans Medicine Fibrinolysin Epithelial Sodium Channels aldosterone business.industry Plasminogen medicine.disease diuretics Endocrinology Diabetes Mellitus Type 2 Creatinine Hypertension Microalbuminuria medicine.symptom Diuretic Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Buhl, K B, Stolzenburg Oxlund, C, Friis, U G, Svenningsen, P, Bistrup, C, Jacobsen, I A & Jensen, B L 2014, ' Plasmin in urine from patients with type 2 diabetes and treatment-resistant hypertension activates ENaC in vitro ', Journal of Hypertension, vol. 32, no. 8, pp. 1672–1677 . https://doi.org/10.1097/HJH.0000000000000216 |
| ISSN: | 0263-6352 |
| DOI: | 10.1097/hjh.0000000000000216 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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