Inhibition of basal nitric oxide synthesis increases aortic augmentation index and pulse wave velocity in vivo

• Published in: British journal of clinical pharmacology Vol. 53; no. 2; pp. 189 - 192
• Main Authors: Wilkinson, Ian B., MacCallum, Helen, Cockcroft, John R., Webb, David J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science, Ltd 01.02.2002; Blackwell Science
• Subjects: Adult; arterial stiffness; Biological and medical sciences; Cardiovascular system; Dose-Response Relationship, Drug; Double-Blind Method; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Heart Rate - drug effects; Hemodynamics - drug effects; Hemodynamics. Rheology; Humans; LNMMA; Male; Medical sciences; Miscellaneous; nitric oxide; Nitric Oxide - physiology; Nitric Oxide Synthase - antagonists & inhibitors; omega-N-Methylarginine - pharmacology; Pharmacology. Drug treatments; pulse wave analysis; Radial Artery - physiology; Short Reports; Vascular Resistance - drug effects; Vertebrates: cardiovascular system; Human; Healthy subject; Enzyme; Enzyme inhibitor; Biological activity; Artery; Nitric-oxide synthase; Vascular resistance; Nitric oxide; Aorta; Arterial pressure; Stiffness; Oxidoreductases; Circulatory system; Hemodynamics
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1046/j.1365-2125.2002.1528adoc.x

Aims  To investigate the role of basal nitric oxide (NO) production in regulating large artery stiffness in vivo. Methods  Incremental doses of the NO synthase inhibitor L‐NG‐monomethyl arginine (LNMMA: 0.1, 0.3, 1.0 and 3.0 mg kg−1 min−1) or placebo were infused in eight healthy men. Arterial stiffness was assessed noninvasively by pulse wave analysis. Results  Compared with placebo, infusion of LNMMA led to a dose‐dependent increase in mean arterial pressure, peripheral vascular resistance, and aortic and systemic arterial stiffness. There was an accompanying reduction in heart rate and cardiac index. The highest dose of LNMMA resulted in an increase of 25% in AIx (95% confidence limits; 12, 38) and of 16 mmHg in mean arterial pressure (9, 23) compared with infusion of saline. Conclusions  These data indicate functional regulation of large artery stiffness in vivo by NO, and may provide new therapeutic strategies for cardiovascular risk reduction.