(Hypertension. 2000;35:1314.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Bradykinin-Induced Vasodilation of Human Forearm Resistance Vessels Is Primarily Mediated by Endothelium-Dependent Hyperpolarization
From the Department of Vascular Medicine and Diabetes (M.L.H.H., T.J.R.) and the Clinical Pharmacology Unit (P.J.M., M.L.H.H.), University Hospital Utrecht, Utrecht, the Netherlands; and Department of Internal Medicine and Clinical Pharmacology (P.S.), University Hospital Nijmegen, Nijmegen, the Netherlands.
Correspondence to Prof Dr Ton J. Rabelink, Department of Vascular Medicine and Diabetes, University Hospital Utrecht, Room F03.226, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands. E-mail T.Rabelink{at}digd.azu.nl
Abstract—Bradykinin (BK) stimulates endothelial cells to release a number of relaxing factors, such as NO, prostanoids (PGs), and an endothelium-derived hyperpolarizing factor (EDHF). However, the contributions of NO, PG, and EDHF in the vascular relaxation to BK vary with species and anatomic origin of blood vessels used. Therefore, the present study was designed to investigate the contributions of NO, PG, and EDHF in vasodilation caused by BK in human forearm resistance vessels. Forearm blood flow (FBF) was recorded with venous occlusion plethysmography in healthy nonsmoking subjects. At first, studies were performed to validate the NO clamp technique for its ability to inhibit endogenous NO generation. Brachial artery infusion of serotonin (0.6, 1.8, and 6 ng · 100 mL forearm volume [FAV]-1 · min-1) caused significant forearm vasodilation (2.6 to 4.6 mL · 100 mL FAV-1 · min-1), which is known to be NO mediated. Indeed, during the NO clamp, cumulative doses of serotonin caused no vasodilation (2.4 to 2.6 mL · 100 mL FAV-1 · min-1), indicating that the generation of endogenous NO was completely blocked. Thereafter, the vasodilative actions of BK were investigated. Brachial artery infusion of BK (50, 100, and 200 ng · 100 mL FAV-1 · min-1) caused significant forearm vasodilation in all studies (from 3.1 to 20.4 mL · 100 mL FAV-1 · min-1). After the inhibition of cyclooxygenase and NO synthase activity through the use of aspirin and the NO-clamp technique, BK increased FBF in a similar manner (3.9 to 18.9 mL · 100 mL FAV-1 · min-1), indicating that the vasodilative actions of BK are independent of NO and PG generation. However, vasodilation caused by the 2 lower doses of BK were significantly attenuated after KCa channel activity was blocked with tetraethylammonium chloride (0.1 mg · 100 mL FAV-1 · min-1), suggesting that in the lower dose range, BK mediates vasodilation through the opening of vascular potassium channels. In conclusion, BK is a potent vasodilator peptide in human forearm resistance vessels, causing vasodilation through hyperpolarization of the vascular wall independent of NO and PG production. In addition, the NO-clamp technique is a valid instrument to investigate the contribution of NO in the vasodilative response to different agents.
Key Words: bradykinin • hyperpolarization • tetraethylammonium chloride • nitric oxide • prostaglandins
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