Smoking impairs bradykinin-stimulated t-PA release

被引:41
作者
Pretorius, M
Rosenbaum, DA
Lefebvre, J
Vaughan, DE
Brown, NJ
机构
[1] Vanderbilt Univ, Med Ctr, Dept Med, Div Clin Pharmacol, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Div Clin Pharmacol, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Div Cardiovasc Med, Nashville, TN 37232 USA
[5] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN 37232 USA
[6] Vet Affairs Med Ctr, Nashville, TN 37212 USA
关键词
bradykinin; t-PA release; smoking; endothelium; plethysmography;
D O I
10.1161/hy0302.105767
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Bradykinin stimulates tissue plasminogen activator release from human endothelium through a flow-independent, 13, receptor-dependent mechanism. The present study tests the hypothesis that smoking impairs bradykinin-stimulated tissue plasminogen activator release. Graded doses of nitroprusside (1.6 to 6.4 mug/min), methacholine (3.2 to 12.8 mug/min), and bradykinin (100 to 400 ng/min) were infused in the brachial artery in random order in 20 smokers and 12 nonsmokers matched for age, gender, and body mass index. Forearm blood flow was measured by strain-gauge plethysmography. All 3 drugs caused a dose-dependent increase in forearm blood flow, with no significant difference between smokers and nonsmokers. Bradykinin (P = 0.001) and methacholine (P = 0.001) caused significant dose-dependent increases in net tissue plasminogen activator release. The tissue plasminogen activator response to bradykinin was significantly greater than the tissue plasminogen activator response to methacholine in the nonsmokers (maximal net tissue plasminogen activator release, 73.2 +/- 21.5 versus 27.6 +/- 7.2 ng/min per 100 mL, P = 0.001) but not in the smokers (maximal net tissue plasminogen activator release, 44.5 +/- 10.7 versus 24.8 +/- 9.3 ng/min per 100 mL; P = 0.154). The effect of bradykinin (P = 0.037), but not methacholine (P = 0.978), on net tissue plasminogen activator release was significantly reduced in smokers compared with nonsmokers. The vascular tissue plasminogen activator response to bradykinin, but not methacholine, is impaired in smokers. Stimulated tissue plasminogen activator release may be a more sensitive measure of endothelial function than vasodilation.
引用
收藏
页码:767 / 771
页数:5
相关论文
共 35 条
[1]   EFFECT OF CHRONIC SMOKING ON FIBRINOLYSIS [J].
ALLEN, RA ;
KLUFT, C ;
BROMMER, EJP .
ARTERIOSCLEROSIS, 1985, 5 (05) :443-450
[2]   LOCAL INHIBITION OF CONVERTING ENZYME AND VASCULAR-RESPONSES TO ANGIOTENSIN AND BRADYKININ IN THE HUMAN FOREARM [J].
BENJAMIN, N ;
COCKCROFT, JR ;
COLLIER, JG ;
DOLLERY, CT ;
RITTER, JM ;
WEBB, DJ .
JOURNAL OF PHYSIOLOGY-LONDON, 1989, 412 :543-555
[3]   G protein-coupled receptor-mediated mitogen-activated protein kinase activation through cooperation of Gαq, and Gαi signals [J].
Blaukat, A ;
Barac, A ;
Cross, MJ ;
Offermanns, S ;
Dikic, I .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (18) :6837-6848
[4]  
Brown NJ, 2000, CIRCULATION, V102, P2190
[5]   Bradykinin stimulates tissue plasminogen activator release in human vasculature [J].
Brown, NJ ;
Gainer, JV ;
Stein, CM ;
Vaughan, DE .
HYPERTENSION, 1999, 33 (06) :1431-1435
[6]   Identification of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factors [J].
Campbell, WB ;
Gebremedhin, D ;
Pratt, PF ;
Harder, DR .
CIRCULATION RESEARCH, 1996, 78 (03) :415-423
[7]   CIGARETTE-SMOKING IS ASSOCIATED WITH DOSE-RELATED AND POTENTIALLY REVERSIBLE IMPAIRMENT OF ENDOTHELIUM-DEPENDENT DILATION IN HEALTHY-YOUNG ADULTS [J].
CELERMAJER, DS ;
SORENSEN, KE ;
GEORGAKOPOULOS, D ;
BULL, C ;
THOMAS, O ;
ROBINSON, J ;
DEANFIELD, JE .
CIRCULATION, 1993, 88 (05) :2149-2155
[8]   THE RELATIONSHIP OF ACTIVE AND PASSIVE SMOKING TO CAROTID ATHEROSCLEROSIS 12-14 YEARS LATER [J].
DIEZROUX, AV ;
NIETO, FJ ;
COMSTOCK, GW ;
HOWARD, G ;
SZKLO, M .
PREVENTIVE MEDICINE, 1995, 24 (01) :48-55
[9]  
Emeis J J, 1992, Agents Actions Suppl, V38 ( Pt 2), P285
[10]   PERFUSED RAT HINDLEGS - A MODEL TO STUDY PLASMINOGEN-ACTIVATOR RELEASE [J].
EMEIS, JJ .
THROMBOSIS RESEARCH, 1983, 30 (03) :195-203