Impaired responsiveness to NO in newly diagnosed patients with rheumatoid arthritis

Arterioscler Thromb Vasc Biol. 2002 Oct 1;22(10):1637-41. doi: 10.1161/01.atv.0000033516.73864.4e.

Abstract

Objective: Cardiovascular disease is the major cause of excessive mortality in patients with rheumatoid arthritis (RA). We determined whether endothelial dysfunction characterizes patients with newly diagnosed RA (n=10) compared with normal subjects (control group, n=33) and whether it is reversible with 6 months of anti-inflammatory therapy.

Methods and results: Endothelial function was determined by measuring vasodilatory responses to intrabrachial artery infusions of acetylcholine (ACh at 7.5 and 15 microg/min, low and high dose, respectively), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP, 3 and 10 micro g/min), an endothelium-independent vasodilator. Before treatment, blood flow responses (fold increase in flow) to low-dose SNP were 30% lower in the RA versus the control group (4.1+/-0.4-fold versus 5.9+/-0.5-fold, respectively), and responses to high-dose SNP were 34% lower in the RA group versus the control group (5.1+/-0.6-fold versus 7.7+/-0.7-fold, respectively; P<0.001). The responses to low-dose ACh were 50% lower in the RA group versus the control group (3.0+/-0.5-fold versus 6.6+/-0.7-fold, respectively), and responses to high-dose ACh were 37% lower in the RA group versus the control group (5.0+/-0.4-fold versus 7.9+/-0.8-fold, respectively; P<0.001). After therapy, clinical and laboratory markers of inflammation had significantly decreased. Blood flow responses to ACh increased significantly (P=0.02).

Conclusions: We conclude that newly diagnosed patients with RA have vascular dysfunction, which is reversible with successful therapy. Therefore, early suppression of inflammatory activity may reduce long-term vascular damage.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Administration, Oral
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use
  • Apoproteins / blood
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / metabolism*
  • Endothelium, Vascular / physiopathology
  • Female
  • Forearm / blood supply
  • Humans
  • Lipids / blood
  • Lipoproteins / blood
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism
  • Nitric Oxide / physiology*
  • Nitric Oxide Donors / metabolism
  • Nitric Oxide Donors / pharmacology
  • Nitroprusside / metabolism
  • Nitroprusside / pharmacology
  • Prednisone / administration & dosage
  • Prednisone / therapeutic use
  • Vascular Resistance / drug effects
  • Vascular Resistance / physiology
  • Vasodilator Agents / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Apoproteins
  • Lipids
  • Lipoproteins
  • Nitric Oxide Donors
  • Vasodilator Agents
  • Nitroprusside
  • Nitric Oxide
  • Acetylcholine
  • Prednisone