The Role of Nitric Oxide Synthase Isoforms in the Cardiovascular Effects of Air Pollution

University of Edinburgh16 enrolled

Overview

Exposure to air pollution has been linked to increased cardiorespiratory morbidity and mortality. The exact component of air pollution that mediates this effect is unknown, but the link is strongest for fine combustion derived particulate matter derived from traffic sources. Recently, it has been demonstrated that inhalation of diesel exhaust impairs vascular vasomotor tone and endogenous fibrinolysis. The mechanism underlying these detrimental vascular is unclear, but is thought to be via oxidative stress and altered bioavailability of endogenous nitric oxide. In these studies we plan to elucidate the role of endogenous nitric oxide synthase isoforms (NO) in the adverse vascular responses observed following exposure to diesel exhaust.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Endothelial Dysfunction

Interventions

Forearm venous occlusion plethysmography to measure forearm blood flow during intrabrachial infusion of nitric oxide synthase inhibitors L-NMMA (2-8 µg/min), S-methionyl-L-citrulline (25-200 nmol/min) and 1400W (100-1000 nmol/min) and positive control norepinephrine (60-540 pmol/min)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy volunteers Exclusion Criteria: * Regular medication use (except oral contraceptive pill) * Current smokers * Significant occupational exposure to air pollution * Intercurrent illness

Outcomes

Primary Outcomes

Forearm blood flow measured by venous occlusion plethysmography during intraarterial infusion of nitric oxide synthase inhibitors L-NMMA, SMTC and 1400W and positive control norepinephrine.

Time frame: 2-4 hours after exposure

Secondary Outcomes

Plasma nitrite concentration

Time frame: During forearm study