Low-dose spironolactone reduces plasma fibulin-1 levels in patients with type 2 diabetes and resistant hypertension

Diabetic patients with hypertension are at particularly high risk of vascular damage and consequently cardiovascular and renal disease. Fibulin-1, an extracellular matrix glycoprotein, is increased in arterial tissue and plasma from individuals with type 2 diabetes. This study aimed to evaluate whet...

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Bibliographic Details
Published in:Journal of human hypertension 2015-01, Vol.29 (1), p.28-32
Main Authors: Oxlund, C S, Cangemi, C, Henriksen, J E, Jacobsen, I A, Gram, J, Schousboe, K, Tarnow, L, Argraves, W S, Rasmussen, L M
Format: Article
Language:English
Subjects:
Aged
Antihypertensive Agents - administration & dosage
Antihypertensives
Biomarkers - blood
Blood pressure
Blood Pressure - drug effects
Calcium-Binding Proteins - blood
Denmark
Diabetes
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - diagnosis
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - physiopathology
Diuretics - administration & dosage
Dose-response relationship (Biochemistry)
Double-Blind Method
Down-Regulation
Drug therapy
Erectile dysfunction
Extracellular matrix
Female
Glomerular filtration rate
Glycoproteins
Humans
Hypertension
Hypertension - blood
Hypertension - diagnosis
Hypertension - drug therapy
Hypertension - physiopathology
Male
Middle Aged
Mineralocorticoid Receptor Antagonists - administration & dosage
Patient outcomes
Pharmacology, Experimental
Properties
Spironolactone
Spironolactone - administration & dosage
Time Factors
Treatment Outcome
Vascular Remodeling - drug effects
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Summary:Diabetic patients with hypertension are at particularly high risk of vascular damage and consequently cardiovascular and renal disease. Fibulin-1, an extracellular matrix glycoprotein, is increased in arterial tissue and plasma from individuals with type 2 diabetes. This study aimed to evaluate whether antihypertensive treatment with spironolactone changes plasma fibulin-1 levels. In a multicenter, double-blind, randomized, placebo-controlled study, 119 patients with type 2 diabetes and resistant hypertension were included. A dose of spironolactone 25 mg or matching placebo was added to previous treatment at randomization. Blood pressure (BP) and plasma fibulin-1 were measured at baseline and at 16 weeks follow-up. Overall, 112 patients completed the study. All measures of BP were reduced in the spironolactone group at follow-up. Plasma fibulin-1 was significantly reduced after spironolactone treatment (P=0.009), but increased after placebo (P=0.017). Baseline plasma fibulin-1 correlated with BP and estimated glomerular filtration rate. Increased levels of plasma fibulin-1 (P=0.004) were observed in diabetic participants reporting erectile dysfunction as compared with participants who did not. Treatment with low-dose spironolactone reduced plasma fibulin-1 levels in patients with type 2 diabetes and resistant hypertension. This supports the hypothesis that the antihypertensive effect of the mineralocorticoid receptor blocker in part may be due to regression of vascular remodeling.
ISSN:0950-9240
1476-5527
DOI:10.1038/jhh.2014.27