© 1997 American Heart Association, Inc.
Articles |
Endothelium-Dependent Vasodilation and Tissue-Type Plasminogen Activator Release in Borderline Hypertension
From the Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Östra, Heart and Lung Institute, and the Department of Neurology, Institute of Clinical Neuroscience, Sahlgrenska University Hospital/Sahlgrenska (C.J.), Göteborg University, Göteborg, Sweden.
Correspondence to Sverker Jern, MD, Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Östra, S-416 85 Göteborg, Sweden.
Abstract We recently showed that muscarinic receptor
stimulation causes a marked increase in the net release of tissue-type
plasminogen activator (TPA) antigen and
activity across the human forearm in vivo, in conjunction with
endothelium-dependent vasodilation. Because
hypertension has been associated with endothelial
dysfunction, the aim of the study was to compare forearm TPA release
and vasodilation in response to muscarinic stimulation in normotensive
(NC) and borderline hypertensive (BH) subjects. The study was performed
in 10 apparently healthy young men with BH and 10 male NC subjects.
Methacholine (MCh: 0.1, 0.8, and 4.0 µg/min) and sodium nitroprusside
(SNP: 0.5, 2.5, and 10 µg/min) were administered in randomized order
as double-blind, stepwise, intrabrachial artery infusions. Forearm
blood flow was assessed by plethysmography. Net release/uptake was
calculated as the product of the arteriovenous concentration
gradient and forearm plasma flow. Vasodilator responses to MCh were
similar in both groups (P=NS), whereas the decrease in
forearm vascular resistance in response to SNP was somewhat less in BH
subjects (P=.005). At rest, both groups showed a significant
arteriovenous gradient and net release of TPA antigen across the
forearm (P<.05 throughout). However, in contrast to the
significant net increment in TPA activity across the forearm in the NC
group (P<.018), BH subjects had no basal forearm increment
in TPA activity (NC vs BH, P=.006). Arterial and
venous plasma levels of plasminogen activator
inhibitor 1 (PAI-1) antigen and activity were higher in BH
subjects (P
.05 throughout), who in contrast to NC
subjects, also had a significant forearm net release of PAI-1 antigen
(P=.006). Across the whole group, there was a significant
inverse relation between arterial PAI-1 antigen levels and
increment in TPA activity across the forearm (r=-.57,
P=.008) but no relation to TPA antigen release. In response
to MCh infusion, both the net release of TPA antigen and increment in
TPA activity increased markedly and to similar extents in both groups
(P<.01 throughout). SNP infusion had no effect on either
TPA antigen release or increment in TPA activity in the NC group but
elicited a significant net release of TPA antigen and increase in TPA
activity in the BH group (P<.05). Both circulating levels
and local release of PAI-1 antigen were significantly correlated to
fasting plasma insulin. Endothelium-dependent
vasodilation and endothelial TPA release in response to
muscarinic receptor stimulation were preserved in BH subjects. At rest,
BH subjects had higher circulating PAI-1 antigen levels and a
corresponding decrease in circulating levels and local increment of TPA
activity. In contrast to NC subjects, BH subjects responded with a TPA
release also in response to increased flow, which may indicate an
enhanced endothelial cell responsiveness to fluid shear
stress.
Key Words: hypertension • muscarinic receptors • TPA • PAI-1
This article has been cited by other articles:
 |
|
 |
|
  G. P. Van Guilder, G. L. Hoetzer, J. J. Greiner, B. L. Stauffer, and C. A. DeSouza Metabolic syndrome and endothelial fibrinolytic capacity in obese adults Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2008; 294(1): R39 - R44. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. Van Guilder, G. L. Hoetzer, D. T. Smith, H. M. Irmiger, J. J. Greiner, B. L. Stauffer, and C. A. DeSouza Endothelial t-PA release is impaired in overweight and obese adults but can be improved with regular aerobic exercise Am J Physiol Endocrinol Metab, November 1, 2005; 289(5): E807 - E813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. L Hoetzer, B. L Stauffer, H. M Irmiger, M. Ng, D. T Smith, and C. A DeSouza Acute and chronic effects of oestrogen on endothelial tissue-type plasminogen activator release in postmenopausal women J. Physiol., September 1, 2003; 551(2): 721 - 728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-A. Bjorkman, S. Jern, and C. Jern Cardiac Sympathetic Nerve Stimulation Triggers Coronary t-PA Release Arterioscler Thromb Vasc Biol, June 1, 2003; 23(6): 1091 - 1097. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Hoetzer, B. L. Stauffer, J. J. Greiner, Y. Casas, D. T. Smith, and C. A. DeSouza Influence of oral contraceptive use on endothelial t-PA release in healthy premenopausal women Am J Physiol Endocrinol Metab, January 1, 2003; 284(1): E90 - E95. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. T Smith, G. L Hoetzer, J. J Greiner, B. L Stauffer, and C. A DeSouza Effects of ageing and regular aerobic exercise on endothelial fibrinolytic capacity in humans J. Physiol., January 1, 2003; 546(1): 289 - 298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. S. Muldowney III and D. E. Vaughan Tissue-type plasminogen activator release: New frontiers in endothelial function J. Am. Coll. Cardiol., September 4, 2002; 40(5): 967 - 969. [Full Text] [PDF]
|
|
|
|
 |
|
 J. P.J. Halcox, W. H. Schenke, G. Zalos, R. Mincemoyer, A. Prasad, M. A. Waclawiw, K. R.A. Nour, and A. A. Quyyumi Prognostic Value of Coronary Vascular Endothelial Dysfunction Circulation, August 6, 2002; 106(6): 653 - 658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pretorius, D. A. Rosenbaum, J. Lefebvre, D. E. Vaughan, and N. J. Brown Smoking Impairs Bradykinin-Stimulated t-PA Release Hypertension, March 1, 2002; 39(3): 767 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. O. Toikka, H. Laine, M. Ahotupa, A. Haapanen, J. S. A. Viikari, J. J. Hartiala, and O. T Raitakari Increased Arterial Intima-Media Thickness and In Vivo LDL Oxidation in Young Men With Borderline Hypertension Hypertension, December 1, 2000; 36(6): 929 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Sjogren, R. Doroudi, L.-m. Gan, L. Jungersten, T. Hrafnkelsdottir, and S. Jern Elevated Intraluminal Pressure Inhibits Vascular Tissue Plasminogen Activator Secretion and Downregulates Its Gene Expression Hypertension, April 1, 2000; 35(4): 1002 - 1008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bertuglia and A. Colantuoni Protective effects of leukopenia and tissue plasminogen activator in microvascular ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, March 1, 2000; 278(3): H755 - H761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Brown, J. V. Gainer, C. M. Stein, and D. E. Vaughan Bradykinin Stimulates Tissue Plasminogen Activator Release in Human Vasculature Hypertension, June 1, 1999; 33(6): 1431 - 1435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Dell'Omo, L. Ferrini, M. Morale, F. De Negri, E. Melillo, F. Carmassi, and R. Pedrinelli Acetylcholine-Mediated Vasodilatation and Tissue-type Plasminogen Activator Release in Normal and Hypertensive Men Angiology, April 1, 1999; 50(4): 273 - 282. [Abstract] [PDF]
|
|
|
|
|
|
C. Jern, P. Ladenvall, U. Wall, and S. Jern Gene Polymorphism of t-PA is Associated With Forearm Vascular Release Rate of t-PA Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 454 - 459. [Abstract] [Full Text] [PDF]
|
|