Conditions: Hyperlipidemia
Keywords: hyperlipidaemia EDHF FMD
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 174
Healthy volunteers: yes

Brief summary:
The purpose of this study is to elucidate the role Endothelium-Derived Hyperpolarizing Factor (EDHF) plays in dilating blood vessels and whether it differs between healthy people and those with high cholesterol. A second purpose of the study is to determine the identity of EDHF.

Detailed description:
The vascular endothelium synthesizes at least four potent vasodilator substances: nitric oxide (NO), prostacyclin, carbon monoxide and endothelium-derived hyperpolarizing factor (EDHF) that contribute to vasodilator tone, and to inhibition of platelet activation and inflammation. EDHF release is stimulated by receptor-dependent agonists such as acetylcholine and bradykinin (BK), and leads to hyperpolarization of the underlying smooth muscle cells presumably by opening Ca2+-activated K+ channels. Indirect pharmacological evidence suggests that EDHF is a cytochrome P450-derived arachidonic acid metabolite, presumably an epoxide. Although the pivotal role of NO to conduit vessel dilation in response to acute increases in shear stress is well known, its' contribution to dilation with sustained increases in flow are minimal, and may be due to EDHF release.

Arms:
arm 1: Healthy subjects had venous occlusion plethysmography after intra-arterial infusions of saline, L-NG-monomethyl Arginine (L-NMMA), Tetraethylammonium (TEA), fluconazole, bradykinin, sodium nitroprusside and acetylcholine arm 2: Non-hypertensive subjects with cardiovascular risk factors had venous occlusion plethysmography after intra-arterial infusions of saline, L-NG-monomethyl Arginine (L-NMMA), Tetraethylammonium (TEA), fluconazole, bradykinin, sodium nitroprusside and acetylcholine

Interventions: intervention 1: Tetraethylammonium (TEA) intervention 2: L-NG-monomethyl Arginine (L-NMMA) intervention 3: Bradykinin intervention 4: Sodium nitroprusside intervention 5: Acetylcholine intervention 6: Saline intervention 7: Fluconazole
Intervention descriptions: intervention 1: 5 minute intra-arterial infusion of Tetraethylammonium at 1 mg/min intervention 2: 5 minute intra-arterial infusion of L-NMMA 8 μmol/min intervention 3: Intra-arterial infusion of bradykinin at 100, 200, and 400 ng/min. Each dose will be given for 5 minutes. intervention 4: Intra-arterial infusion of sodium nitroprusside at 1.6 and 3.2 mg/min. Each dose will be given for 5 minutes. intervention 5: Intra-arterial infusion of acetylcholine at 7.5, 15 and 30 μg/min. Each dose will be given for 5 minutes. intervention 6: 5 minute intra-arterial infusion of 0.9% saline at 2.5ml/min intervention 7: 5 minute intra-arterial infusion of fluconazole at 0.4 mg/L/min

Protocol document: