The influence of chronic inhibition of nitric oxide synthesis on contractile and relaxant properties of rat carotid and mesenteric arteries

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2000-12, Vol.362 (6), p.504-511
• Main Authors: Heijenbrok, F J, Mathy, M J, Pfaffendorf, M, van Zwieten, P A
• Format: Article
• Language: English
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology; Adrenergic alpha-Agonists - pharmacology; Adrenergic beta-Agonists - pharmacology; Animals; Carotid Artery, Common - drug effects; Carotid Artery, Common - metabolism; Carotid Artery, Common - physiology; Colforsin - pharmacology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiology; Enzyme Inhibitors - pharmacology; Isometric Contraction - drug effects; Isometric Contraction - physiology; Isoproterenol - pharmacology; Male; Mesenteric Arteries - drug effects; Mesenteric Arteries - metabolism; Mesenteric Arteries - physiology; Methacholine Chloride - pharmacology; Muscarinic Agonists - pharmacology; Muscle Relaxation - drug effects; Muscle Relaxation - physiology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiology; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - biosynthesis; Phenylephrine - pharmacology; Potassium Chloride - pharmacology; Rats; Rats, Wistar; Receptor, Muscarinic M3; Receptors, Adrenergic, beta - physiology; Receptors, Muscarinic - physiology; Vasoconstrictor Agents - pharmacology; Vasodilation - physiology
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s002100000254

Balloon denudation of the rat carotid artery leads to an immediate decrease in beta-adrenoceptor-medi-ated vasodilator response. However, this arterial function becomes significantly enhanced during subsequent formation of neointima with the endothelial cell lining still being absent. It was therefore hypothesized that chronic suppression of endothelium-dependent nitric oxide (NO) synthesis may eventually upregulate the beta-adrenoceptor system on vascular smooth muscle. To investigate this hypothesis, male Wistar rats were treated chronically with the L-arginine analogue NG-nitro-L-arginine methyl ester (L-NAME) to inhibit the synthesis of NO (i.e. 15 mg/kg per day or 0.06 mmol/kg per day for 6 weeks p.o.). Prior to the experiments the mean arterial blood pressure (MAP) was significantly elevated in the L-NAME-treated rats (i.e. 128.4+/-3.4 mmHg vs. 100.0+/-2.9 mmHg, L-NAME vs. control, n=4, P