Endothelial Hyperpolarization in Humans

Emory University

Status and phase: Terminated; Phase 2

Conditions: Hyperlipidemia

Treatments: Drug: Fluconazole; Drug: Acetylcholine; Drug: L-NG-monomethyl Arginine (L-NMMA); Drug: Saline; Drug: Sodium nitroprusside; Drug: Bradykinin; Drug: Tetraethylammonium (TEA)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00166166

IRB00021886

0605-2002 (Other Identifier)

1R01HL079115-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 174 patients

Sex: All

Ages: 21 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Hyperlipidemic (LDL > 140)
• Healthy Volunteer

Exclusion criteria

• Pregnancy
• Diabetes mellitus
• Cardiovascular Disease
• Hypertension
• Use of any regular medications
• Renal insufficiency
• Smoking (current or within the past 5 years)
• Bleeding disorder

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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174 participants in 2 patient groups

Healthy Controls

Experimental group

Description:

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

Treatment:

Drug: Saline

Drug: Sodium nitroprusside

Drug: L-NG-monomethyl Arginine (L-NMMA)

Drug: Acetylcholine

Drug: Bradykinin

Drug: Tetraethylammonium (TEA)

Drug: Fluconazole

Risk Factors

Experimental group

Description:

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

Treatment:

Drug: Saline

Drug: Sodium nitroprusside

Drug: L-NG-monomethyl Arginine (L-NMMA)

Drug: Acetylcholine

Drug: Bradykinin

Drug: Tetraethylammonium (TEA)

Drug: Fluconazole