Key result
Acute nitric oxide synthase inhibition cuts small artery compliance ~36% and increases SVR.
Why the study?
Does acute inhibition of nitric oxide synthase with L-NAME alter large and small artery tone in young normal volunteers?
Does acute inhibition of nitric oxide synthase with L-NAME alter large and small artery tone in young normal volunteers?
Absolute Event Rate: 6.5% vs 10.1%
p-value: p=<.001
Acute inhibition of nitric oxide synthase predominantly affects small arteries and arterioles rather than large conduit arteries.
Predominantly affects small arteries in healthy volunteers; extends mechanistic NO data but leaves open disease relevance.
Vascular tone is influenced by endothelial function mediated largely through nitric oxide (NO) release. To evaluate the influence of basal NO release on arterial tone L-NAME (1.5 to 5.0 mg/kg) was infused in 7 young normal volunteers and observations made over 6 hours. Arterial tone was evaluated by: 1) pulse wave analysis utilizing a modified Windkessel model allowing separate calculation of large artery capacitive compliance (C1), small artery reflective compliance (C2), and systemic vascular resistance (SVR); 2) brachial artery compliance (BC) by echo-tracking ultrasound; 3) carotid to femoral pulse wave velocity (PWV); and 4) brachial artery flow-mediated vasodilation (FMV). Systolic, diastolic, and mean blood pressure (BP) rose modestly after L-NAME (114 to 125, P<.05; 66 to 76, P<.01; 81 to 92 mmHg, P<.01). Heart rate (HR) tended to fall (63 to 57 bpm, P=NS). C1 was unchanged 16.4 to 17.0 ml/mmH × 10, and PWV 8.32 to 8.65 m/s), BC (5.1 × 10−3 to 6.0 × 10−3 mm2/mmHg, P = NS) and FMV 5.52 to 5.15% also did not change. However, SVR rose 1208 to 1490 dyne · sec · cm−5, P<.01 and C2 fell 10.1 to 6.5 ml/mmHg × 100 P<.001). Thus NO synthase inhibition exhibits its effect predominantly on the small arteries (reflecting sites and arterioles) that are thin-walled and not on the conduit arteries in which NO release by the endothelium may not penetrate the wall.
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M Gilani (2000) studied Healthy volunteers (n=7). L-NAME vs. Baseline was evaluated on Small artery reflective compliance (C2) (p=<.001). Acute inhibition of nitric oxide synthase with L-NAME predominantly affected small arteries, decreasing reflective compliance (P<.001) and increasing systemic vascular resistance (P<.01).
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