Published Online
on July 12, 2004

A more recent version of this article appeared on September 1, 2004

This Article Full Text (PDF) All Versions of this Article: 44/3/300    most recent 01.HYP.0000137380.91476.fbv1 Alert me when this article is cited Alert me if a correction is posted 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 Hrafnkelsdóttir, T. Articles by Jern, S. Search for Related Content PubMed PubMed Citation Articles by Hrafnkelsdóttir, T. Articles by Jern, S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information High Blood Pressure Kidney Diseases Related Collections Other hypertension Fibrinolysis Arterial thrombosis Endothelium/vascular type/nitric oxide

Submitted on November 13, 2003
Revised on December 9, 2003

Impaired Endothelial Release of Tissue-Type Plasminogen Activator in Patients With Chronic Kidney Disease and Hypertension

Thórdís Hrafnkelsdóttir^*; Pia Ottosson; Thorarinn Gudnason; Ola Samuelsson; and Sverker Jern

From the Clinical Experimental Research Laboratory (T.H., T.G., S.J.), Sahlgrenska University Hospital/Östra, and the Department of Nephrology (P.O., O.S.), Sahlgrenska University Hospital/Sahlgrenska, Göteborg University, Sweden.

^* To whom correspondence should be addressed. E-mail: thordis.hrafnkelsdottir{at}hjl.gu.se.

Abstract--We have shown that the capacity for local release of tissue-type plasminogen activator (tPA) from the vascular endothelium is impaired in patients with primary hypertension. Because this response is an important protective mechanism against intravascular clotting, we investigated whether this system is also defective in patients with advanced chronic kidney disease and hypertension. Nine nondiabetic nonsmoking men with chronic kidney disease (glomerular filtration rate 11 to 28 mL/minx1.73 m²; aged 33 to 75 years) were compared with age-matched healthy controls. Intraarterial infusions of desmopressin, methacholine, and sodium nitroprusside were given locally in the brachial artery. Forearm blood flow was measured by venous occlusion plethysmography and blood collected repeatedly during the desmopressin infusion for determination of stimulated net and total cumulated release of tPA. The maximal release rate of active tPA (P<0.05) and the capacity for acute tPA release were markedly impaired in the renal patients as compared with healthy subjects (ANOVA, P=0.013). Accordingly, the accumulated release of tPA was 1905 (SEM 366) and 3387 (718) ng/L tissue, respectively (P<0.05). However, there were no significant differences in vasodilator responses between the groups. Thus, patients with advanced chronic kidney disease and hypertension have a markedly impaired capacity for acute release of tissue plasminogen activator, despite preserved endothelium-dependent vasodilation. This defect may contribute to a defective local defense against arterial thrombosis.

Key words: kidney failure • endothelium • hypertension, essential • tissue-type plasminogen activator • hypertension, renal

This article has been cited by other articles:

				V. Agrawal, B. Rai, J. Fellows, and P. A. McCullough In-hospital outcomes with thrombolytic therapy in patients with renal dysfunction presenting with acute ischaemic stroke Nephrol. Dial. Transplant., November 27, 2009; (2009) gfp619v1. [Abstract] [Full Text] [PDF]

				G. Tsivgoulis, M. Saqqur, V. K. Sharma, A. Y. Lao, M. D. Hill, A. V. Alexandrov, and for the CLOTBUST Investigators Association of Pretreatment Blood Pressure With Tissue Plasminogen Activator-Induced Arterial Recanalization in Acute Ischemic Stroke Stroke, March 1, 2007; 38(3): 961 - 966. [Abstract] [Full Text] [PDF]

				S. G. Wannamethee, A. G. Shaper, G. D.O. Lowe, L. Lennon, A. Rumley, and P. H. Whincup Renal function and cardiovascular mortality in elderly men: the role of inflammatory, procoagulant, and endothelial biomarkers Eur. Heart J., December 2, 2006; 27(24): 2975 - 2981. [Abstract] [Full Text] [PDF]

				W. Ridderstrale, E. Ulfhammer, S. Jern, and T. Hrafnkelsdottir Impaired Capacity for Stimulated Fibrinolysis in Primary Hypertension Is Restored by Antihypertensive Therapy Hypertension, April 1, 2006; 47(4): 686 - 691. [Abstract] [Full Text] [PDF]

				J. J. Oliver, D. J. Webb, and D. E. Newby Stimulated Tissue Plasminogen Activator Release as a Marker of Endothelial Function in Humans Arterioscler Thromb Vasc Biol, December 1, 2005; 25(12): 2470 - 2479. [Abstract] [Full Text] [PDF]