OBJECTIVES: The goal of this study was to assess whether endothelial dysfunction occurs in the forearm venous capacitance bed of patients with chronic heart failure (CHF) and to determine the role of nitric oxide (NO) in modulating venous tone. BACKGROUND: Control of venous tone is crucially important in CHF. More than 70% of blood volume lies in the venous capacitance beds. Therefore, small changes in venous tone may markedly affect cardiac filling pressures and cardiac output. METHODS: Venous tone was measured using radionuclide forearm venous plethysmography in 24 patients with CHF and 16 age-matched controls. The effect of basal NO activity on venous tone was assessed by infusing N-monomethyl-L-arginine 12 mg/min and stimulated NO using carbachol 15 microg/min. Brachial artery flow-mediated dilation was assessed by ultrasonic wall-tracking. RESULTS: Blockade of basal NO release caused a significant and similar venoconstriction in patients (9.6 +/- 1.8%, p < 0.01) and controls (6.6 +/- 1.7%, p < 0.01). Carbachol-induced venodilation was significant and similar in patients (36.8 +/- 3.9%, p < 0.001) and controls (40.7 +/- 3.9%, p < 0.001). Brachial artery flow-mediated dilation was impaired in patients compared with controls (2.0 +/- 0.6% vs. 7.5 +/- 2.5%, p < 0.01). CONCLUSIONS: Our data indicate that, despite marked impairment of the function of the arterial endothelium, there is preservation of both basal and stimulated NO release in the forearm venous capacitance bed. This may provide important insights into mechanisms of endothelial dysfunction in CHF and the potential for novel therapy.
OBJECTIVES: The goal of this study was to assess whether endothelial dysfunction occurs in the forearm venous capacitance bed of patients with chronic heart failure (CHF) and to determine the role of nitric oxide (NO) in modulating venous tone. BACKGROUND: Control of venous tone is crucially important in CHF. More than 70% of blood volume lies in the venous capacitance beds. Therefore, small changes in venous tone may markedly affect cardiac filling pressures and cardiac output. METHODS: Venous tone was measured using radionuclide forearm venous plethysmography in 24 patients with CHF and 16 age-matched controls. The effect of basal NO activity on venous tone was assessed by infusing N-monomethyl-L-arginine 12 mg/min and stimulated NO using carbachol 15 microg/min. Brachial artery flow-mediated dilation was assessed by ultrasonic wall-tracking. RESULTS: Blockade of basal NO release caused a significant and similar venoconstriction in patients (9.6 +/- 1.8%, p < 0.01) and controls (6.6 +/- 1.7%, p < 0.01). Carbachol-induced venodilation was significant and similar in patients (36.8 +/- 3.9%, p < 0.001) and controls (40.7 +/- 3.9%, p < 0.001). Brachial artery flow-mediated dilation was impaired in patients compared with controls (2.0 +/- 0.6% vs. 7.5 +/- 2.5%, p < 0.01). CONCLUSIONS: Our data indicate that, despite marked impairment of the function of the arterial endothelium, there is preservation of both basal and stimulated NO release in the forearm venous capacitance bed. This may provide important insights into mechanisms of endothelial dysfunction in CHF and the potential for novel therapy.
Authors: Matthias Schmitt; Daniel J Blackman; Gordon W Middleton; John R Cockcroft; Michael P Frenneaux Journal: Br J Clin Pharmacol Date: 2002-12 Impact factor: 4.335