Effect of Systemic Nitric Oxide Synthase Inhibition on Arterial Stiffness in Humans

Abstract

Stiffening of large elastic arteries impairs the buffering function of the arterial system and contributes to cardiovascular disease. Vascular tone is an important determinant of arterial stiffness. PURPOSE: To determine whether endothelium-derived nitric oxide modulates stiffness of large elastic artery in humans. METHODS: Seven apparently healthy adults (60±3 yr, 2 males and 5 females) underwent systemic alpha-adrenergic blockade (phentolamine) and systemic nitric oxide synthase inhibition using NG-monomethyl-L-arginine (L-NMMA) in sequence. Phentolamine was given first to isolate the contribution of nitric oxide to arterial stiffness by preventing reflex changes in sympathetic tone that result from systemic nitric oxide synthase inhibition as well as to test the extent to which sympathetic nervous system activity modulates arterial stiffness. RESULTS: Mean arterial pressure decreased (P<0.05) after phentolamine infusion, but returned to baseline levels after L-NMMA infusion. Carotid β -stiffness index (via simultaneous B-mode ultrasound and applanation tonometry on the common carotid artery) did not change after the restraint of systemic alpha-adrenergic nerve activity (9.8±1.2 vs. 9.1±1.1 U), but increased (P<0.05) after NO synthase inhibition (12.6±2.0 U). Similarly, aortic pulse wave velocity (PWV) did not change after phentolamine infusion (862±49 vs. 821±51 cm/sec), but increased (P<0.05) after L-NMMA infusion (982±69 cm/sec). Femoral artery β -stiffness index and leg PWV, measures of peripheral arterial stiffness, did not change significantly throughout the experiments. CONCLUSION: Nitric oxide appears to modulate central arterial stiffness in humans.