Mechanism of thrombin-induced vasodilation in human coronary arterioles. Am J Physiol Heart Circ Physiol 2003 Apr;284(4):H1080-6
Date
02/22/2003Pubmed ID
12595282DOI
10.1152/ajpheart.00465.2002Scopus ID
2-s2.0-0037379059 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
Thrombin (Thromb), activated as part of the clotting cascade, dilates conduit arteries through an endothelial pertussis toxin (PTX)-sensitive G-protein receptor and releases nitric oxide (NO). Thromb also acts on downstream microvessels. Therefore, we examined whether Thromb dilates human coronary arterioles (HCA). HCA from right atrial appendages were constricted by 30-50% with endothelin-1. Dilation to Thromb (10(-4)-1 U/ml) was assessed before and after inhibitors with videomicroscopy. There was no tachyphylaxis to Thromb dilation (maximum dilation = 87.0%, ED(50) = 1.49 x 10(-2)). Dilation to Thromb was abolished with either hirudin or denudation but was not affected by PTX. Neither N(omega)-nitro-l-arginine methyl ester (n = 7), indomethacin (n = 9), (1)H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (n = 6), tetraethylammonium chloride (n = 5), nor iberiotoxin (n = 4) reduced dilation to Thromb. However, KCl (maximum dilation = 89 +/- 5 vs. 20 +/- 10%; P < 0.05; n = 7), tetrabutylammonium chloride (maximum dilation = 79 +/- 7 vs. 21 +/- 4%; P < 0.05; n = 5), and charybdotoxin (maximum dilation = 89 +/- 4 vs. 10 +/- 2%; P < 0.05; n = 4) attenuated dilation to Thromb. In contrast to animal models, Thromb-induced dilation in human arterioles is independent of G(i)-protein activation and NO release. However, Thromb dilation is endothelium dependent, is maintained on consecutive applications, and involves activation of K(+) channels. We speculate that an endothelium-derived hyperpolarizing factor contributes to Thromb-induced dilation in HCA.
Author List
Bosnjak JJ, Terata K, Miura H, Sato A, Nicolosi AC, McDonald M, Manthei SA, Saito T, Hatoum OA, Gutterman DDMESH terms used to index this publication - Major topics in bold
AdultAged
Arterioles
Cardiovascular Diseases
Charybdotoxin
Chlorates
Coronary Vessels
Endothelin-1
Endothelium, Vascular
Female
GTP-Binding Protein alpha Subunits, Gi-Go
Hirudins
Humans
In Vitro Techniques
Male
Microscopy, Video
Middle Aged
Nitric Oxide
Pertussis Toxin
Potassium Chloride
Quaternary Ammonium Compounds
Risk Factors
Thrombin
Vasodilation