title: Microvascular Endothelial Dysfunction and Enhanced Thromboxane and Endothelial Contractility in Patients with HIV.
abstract: The prevalence of cardiovascular disease is increased with human immunodeficiency virus (HIV) infection, but the mechanism is unclear. We hypothesized that HIV increases microvascular reactive oxygen species, thereby impairing endothelial function and enhancing contractility.
  Subcutaneous microarterioles were isolated from gluteal skin biopsies in premenopausal, African American, HIV positive women receiving effective anti-retroviral therapy, but without cardiovascular risk factors except for increased body mass index (n=10) and healthy matched controls (n=10). The arterioles were mounted on myographs, preconstricted and relaxed with acetylcholine for: endothelium-dependent relaxation, endothelium-dependent relaxation factor (nitric oxide synthase-dependent relaxation), endothelium-dependent hyperpolarizing factor (potassium-channel dependent relaxation) and endothelium-independent relaxation (nitroprusside). Contractions were tested to endothelium-dependent contracting factor (acetylcholine contraction with blocked relaxation); phenylephrine, U-46,619 and endothelin-1. Plasma L-arginine and asymmetric dimethylarginine were measured by high performance capillary electrophoresis.
  The micro-arterioles from HIV positive women had significantly (% change in tension; P<0.05) reduced acetylcholine relaxation (-51 ± 6 vs. -78 ± 3%), endothelium-dependent relaxation factor (-28 ± 4 vs. -39 ± 3%), endothelium-dependent hyperpolarizing factor (-17 ± 4 vs. -37 ± 4%) and decreased nitric oxide activity (0.16 ± 0.03 vs. 0.70 ± 0.16 Δ unit) but unchanged nitroprusside relaxation. They had significantly enhanced endothelium-dependent contracting factor (+21 ± 6 vs. +7 ± 2%) and contractions to U-46,619 (+164 ± 10 vs. +117 ± 11%) and endothelin-1(+151 ± 12 vs. +97 ± 9%), but not to phenylephrine. There was enhanced reactive oxygen species with acetylcholine (0.11 ± 0.02 vs. 0.05 ± 0.01 Δ unit; P<0.05) and endothelin-1 (0.31 ± 0.06 vs. 0.10 ± 0.02 Δ unit; P<0.05). Plasma L-arginine: assymetric dimethyl arginine rates was reduced (173 ± 12 vs. 231 ± 6 μmol·μmol-1, P<0.05).
  Premenopausal HIV positive womenhad microvascular oxidative stress with severe endothelial dysfunction and reduced nitric oxide and arginine: assymetric dimethylarginine ratio but enhanced endothelial, thromboxane and endothelin contractions. These microvascular changes may herald later cardiovascular disease.
authors: Hypertension, Kidney and Vascular Research Center and the Division of Nephrology and Hypertension, Georgetown University, USA.
authors: Dan
authors: D
authors: Wang
authors: Transplant Institute, Georgetown University, USA.
authors: Joseph K
authors: JK
authors: Melancon
authors: Transplant Institute, Georgetown University, USA.
authors: Jennifer
authors: J
authors: Verbesey
authors: Division of Infectious Disease and the Metropolitan Washington Women's HIV Study group, Georgetown University, Washington, USA.
authors: Haihong
authors: H
authors: Hu
authors: Division of Infectious Disease and the Metropolitan Washington Women's HIV Study group, Georgetown University, Washington, USA.
authors: Chenglong
authors: C
authors: Liu
authors: Hypertension, Kidney and Vascular Research Center and the Division of Nephrology and Hypertension, Georgetown University, USA.
authors: Shakil
authors: S
authors: Aslam
authors: Division of Infectious Disease and the Metropolitan Washington Women's HIV Study group, Georgetown University, Washington, USA.
authors: Mary
authors: M
authors: Young
authors: Hypertension, Kidney and Vascular Research Center and the Division of Nephrology and Hypertension, Georgetown University, USA.
authors: Christopher S
authors: CS
authors: Wilcox
keywords: Asymmetric dimethylarginine (ADMA); Cardiovascuar disease (CVD); Endothelial dysfunction; Endothelin-1 (ET-1); Endothelium-dependent relaxing factor (EDRF); Nitric oxide (NO); Reactive oxygen species (ROS); Thromboxane-prostanoid receptors (TP-Rs)