L-arginine-dependent vascular smooth muscle relaxation and cGMP formation

• Published in: The American journal of physiology Vol. 259; no. 6 Pt 2; p. H1813
• Main Authors: Gold, M E, Wood, K S, Byrns, R E, Buga, G M, Ignarro, L J
• Format: Journal Article
• Language: English
• Published: United States 01.12.1990
• Subjects: Animals; Arginine - analogs & derivatives; Arginine - pharmacology; Arginine - physiology; Cattle; Cyclic GMP - metabolism; Endothelium, Vascular - physiology; Microscopy, Electron, Scanning; Muscle Relaxation; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiology; Nitric Oxide - metabolism; Pulmonary Artery - drug effects; Pulmonary Artery - metabolism; Pulmonary Artery - physiology
• ISSN: 0002-9513; 2163-5773
• DOI: 10.1152/ajpheart.1990.259.6.h1813

The objective of this study was to ascertain whether endothelium-dependent relaxation and guanosine 3',5'-cyclic monophosphate (cGMP) formation in bovine pulmonary artery are dependent on L-arginine. Arterial rings responded to acetylcholine and A23187 with increased cGMP accumulation and relaxation and showed resting L-arginine levels of approximately 300 microM. Addition of L-arginine failed to cause relaxation or cGMP accumulation. Arterial rings incubated under tension at 37 degree C for 24 h showed a three- to fourfold decline in L-arginine levels, and this decline was accompanied by a similar decline in resting cGMP levels as well as complete refractoriness to endothelium-dependent relaxation and cGMP formation in response to acetylcholine and A23187, without alteration of responsiveness to nitric oxide, s-nitrosothiols, or nitroglycerin. The endothelium in 24-h incubated arterial rings was normal morphologically, as assessed by scanning electron microscopy. L-Arginine caused endothelial-dependent relaxation and cGMP formation in L-arginine-depleted rings, which was antagonized by oxyhemoglobin and methylene blue. Bovine aortic endothelial cells grown in L-arginine-deficient medium supplemented with D-arginine during the final 24 h of growth failed to generate endothelium-derived nitric oxide, as assessed by bioassay cascade. L-Canavanine, but not L-lysine or L-ornithine, protected against the decline in L-arginine and cGMP levels and loss of endothelium-dependent relaxation that was characteristic of 24-h incubated arterial rings. The pharmacological properties of L-arginine were shared by L-arginine ethyl ester, L-arginine methyl ester, and L-homoarginine but not N-alpha-benzoyl-L-arginine ethyl ester or L-canavanine. These observations indicate that L-arginine or a structural analogue may be obligatory for endothelium-dependent relaxation and cGMP formation.