Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

OBJECTIVES: Our aim was to investigate mechanisms of inflammation-induced endothelial dysfunction in humans. METHODS: Endothelial function in twenty-one healthy human volunteers was measured using forearm venous plethysmography before and 8 h after administration of typhoid vaccination to generate an inflammatory response. Basal and stimulated endothelial nitric oxide (NO) bioavailability was assessed by measurement of the responses to intra-arterial N(G)-monomethyl-l-arginine (l-NMMA) and bradykinin, respectively. The effects of supplementation with l-arginine or ascorbic acid were assessed to probe the effects of substrate deficiency and oxidative stress, respectively. Systemic effects were determined by measuring cytokine response, total anti-oxidant status (TAOS) and urinary protein excretion. RESULTS: Vaccination induced a cytokine response, a fall in total anti-oxidant status and increased urinary albumin excretion (UAE). There was a reduction in the response to bradykinin (BK, P<0.005) and l-NMMA (P<0.0001) with no effect on the response to glyceryl trinitrate (GTN) and norepinephrine (NE). Following vaccination blood flow response to BK (but not GTN) was partially returned to pre-vaccine levels by infusion of ascorbic acid (P=0.01). Supplementation with l-arginine had no effect. CONCLUSION: Inflammation causes widespread endothelial dysfunction, reduces vascular NO bioavailability and increases oxidative stress. These actions are partially reversible with local anti-oxidants. These findings suggest a role for reactive oxygen species in inflammation-induced endothelial dysfunction.

Original publication

DOI

10.1016/j.cardiores.2004.06.020

Type

Journal article

Journal

Cardiovasc Res

Publication Date

01/10/2004

Volume

64

Pages

172 - 178

Keywords

Adult, Albuminuria, Analysis of Variance, Arginine, Ascorbic Acid, Biological Availability, Bradykinin, Dose-Response Relationship, Drug, Endothelium, Vascular, Female, Forearm, Humans, Male, Nitric Oxide, Nitroglycerin, Norepinephrine, Oxidative Stress, Plethysmography, Regional Blood Flow, Statistics, Nonparametric, Typhoid-Paratyphoid Vaccines, Vasoconstrictor Agents, Vasodilator Agents, omega-N-Methylarginine