This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 46/2/313    most recent 01.HYP.0000174327.53863.86v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ma, J. Articles by Brown, N. J. Search for Related Content PubMed PubMed Citation Articles by Ma, J. Articles by Brown, N. J. Related Collections Cardiovascular Pharmacology Other hypertension Fibrinolysis Clinical Studies

(Hypertension. 2005;46:313.)
© 2005 American Heart Association, Inc.

Original Articles

Differing Effects of Mineralocorticoid Receptor–Dependent and –Independent Potassium-Sparing Diuretics on Fibrinolytic Balance

Ji Ma; Francisco Albornoz; Chang Yu; Daniel W. Byrne; Douglas E. Vaughan; Nancy J. Brown

From the Divisions of Clinical Pharmacology (J.M., F.A., N.J.B.), Cardiovascular Medicine (F.A., D.E.V.), and General Internal Medicine (D.W.B.), the Departments of Medicine and Pharmacology and Biostatistics (C.Y.), and from the General Clinical Research Center (C.Y., D.W.B.), Vanderbilt University, Nashville, Tenn.

Correspondence to Nancy J. Brown, MD, 560 Robinson Research Building, Vanderbilt University Medical Center, Nashville, TN 37232-6602. E-mail nancy.j.brown{at}vanderbilt.edu

This study tests the hypothesis that spironolactone influences plasminogen activator inhibitor-1 (PAI-1) concentrations through mineralocorticoid receptor antagonism rather than through changes in potassium. Effects of spironolactone (50 mg per day) and triamterene (50 mg per day) on fibrinolytic balance were compared in 18 normotensive and 20 hypertensive subjects pretreated with hydrochlorothiazide (HCTZ; 12.5 mg per day). Blood pressure and serum potassium were similar in spironolactone and triamterene treatment groups. The effect of the 2 drugs on the renin-angiotensin-aldosterone system was also similar. In contrast, spironolactone and triamterene exerted opposing effects on PAI-1 antigen (P=0.006 for drug effect). In normotensive subjects, triamterene (from 10.1±7.8 to 16.9±9.9 ng/mL at 9 AM, P=0.019; from 7.6±5.4 to 11.5±7.3 ng/mL at 11 AM, P=0.027; from 9.3±7.7 to 13.7±8.5 ng/mL for average of all time points, P=0.054) but not spironolactone significantly increased PAI-1 antigen. In hypertensive subjects, spironolactone significantly decreased PAI-1 antigen (from 22.0±23.4 to 16.7±19.0 ng/mL at 10 AM, P=0.041; from 17.5±21.7 to 12.7±16.8 ng/mL at 11 AM, P=0.043; from 20.3±22.6 to 16.6±19.7 ng/mL for average of all time points, P=0.014), whereas there was no effect of triamterene. Only spironolactone significantly decreased the molar ratio of PAI-1 to tissue-type plasminogen activator (t-PA) in hypertensive subjects. By regression analysis, predictors of mean PAI-1 response were spironolactone versus triamterene (P=0.014), hypertension (P=0.002), and PAI-1 response to HCTZ (P=0.019), with a trend for aldosterone (P=0.061). Mineralocorticoid receptor antagonism prevents the effect of activation of the renin-angiotensin-aldosterone system on PAI-1 antigen in normotensive subjects and improves fibrinolytic balance in hypertensive subjects through a potassium-independent mechanism.

Key Words: renin • aldosterone • angiotensin II • plasminogen

This article has been cited by other articles:

				J. M. Luther, Z. Wang, J. Ma, N. Makhanova, H.-S. Kim, and N. J. Brown Endogenous Aldosterone Contributes to Acute Angiotensin II-Stimulated Plasminogen Activator Inhibitor-1 and Preproendothelin-1 Expression in Heart But Not Aorta Endocrinology, May 1, 2009; 150(5): 2229 - 2236. [Abstract] [Full Text] [PDF]

				N. J. Brown Aldosterone and Vascular Inflammation Hypertension, February 1, 2008; 51(2): 161 - 167. [Full Text] [PDF]

				J. M. Luther, J. V. Gainer, L. J. Murphey, C. Yu, D. E. Vaughan, J. D. Morrow, and N. J. Brown Angiotensin II Induces Interleukin-6 in Humans Through a Mineralocorticoid Receptor-Dependent Mechanism Hypertension, December 1, 2006; 48(6): 1050 - 1057. [Abstract] [Full Text] [PDF]

				E. L. Schiffrin Effects of Aldosterone on the Vasculature Hypertension, March 1, 2006; 47(3): 312 - 318. [Full Text] [PDF]

				G. H. Williams Cardiovascular Benefits of Aldosterone Receptor Antagonists: What About Potassium? Hypertension, August 1, 2005; 46(2): 265 - 266. [Full Text] [PDF]