Effect of systemic nitric oxide synthase inhibition on arterial stiffness in humans.
Stiffening of large elastic arteries impairs the buffering function of the arterial system and contributes to cardiovascular disease. The aim of this study was to determine whether endothelium-derived nitric oxide (NO) modulates the stiffness of large elastic arteries in humans. Seven apparently healthy adults (60+/-3 years, 2 males and 5 females) underwent systemic alpha-adrenergic blockade (phentolamine) and systemic NO synthase inhibition using NG-monomethyl-L-arginine (L-NMMA) in sequence. Phentolamine was given first to isolate contribution of NO to arterial stiffness by preventing reflex changes in sympathetic tone that result from systemic NO synthase inhibition, and also to compare arterial stiffness at a similar mean arterial pressure. Mean arterial blood pressure decreased (p<0.05) after phentolamine infusion but returned to baseline levels after L-NMMA infusion. The carotid beta-stiffness index (via simultaneous 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). These results suggest that NO appears to modulate central arterial stiffness in humans.
Sugawara
Jun
J
Institute for Human Science and Biomedical Engineering, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan. jun.sugawara@mail.utexas.edu
Komine
Hidehiko
H
Hayashi
Koichiro
K
Yoshizawa
Mutsuko
M
Yokoi
Takashi
T
Otsuki
Takeshi
T
Shimojo
Nobutake
N
Miyauchi
Takashi
T
Maeda
Seiji
S
Tanaka
Hirofumi
H
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D004548:Elasticity; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors* / Q000502:physiology*; D010646:Phentolamine / Q000008:administration & dosage; D011673:Pulsatile Flow / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D019323:omega-N-Methylarginine / Q000008:administration & dosage*
D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D010646:Phentolamine