Acetylcholine-induced endothelium-dependent vascular smooth muscle relaxation in nitroglycerin-tolerant isolated rat aorta

• Published in: Heart and vessels 1991-09, Vol.6 (3), p.175-180
• Main Authors: NAMIKI, A, AIKAWA, J, MOROI, M, MACHII, K, AKATSUKA, N
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Animals; Antianginal agents. Coronary vasodilator agents; Aorta - drug effects; Aorta - physiology; Biological and medical sciences; Cardiovascular system; Culture Techniques; Cyclic GMP - metabolism; Dose-Response Relationship, Drug; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Male; Medical sciences; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiology; Nitric Oxide - physiology; Norepinephrine - pharmacology; Pharmacology. Drug treatments; Rats; Rats, Inbred Strains; Vasodilation - drug effects; Vasodilation - physiology
• ISSN: 0910-8327; 1615-2573
• DOI: 10.1007/BF02058283

Nitroglycerin (NTG) tolerance is recognized clinically, and its pharmacological mechanism has been thought to be due to a decrease in the accumulation of cyclic GMP (cGMP) which is a second messenger of NTG. Endothelium-derived relaxing factor (EDRF) also relaxes vascular smooth muscle through the activation of soluble guanylate cyclase and the production of cGMP. The purpose of this study was to investigate acetylcholine (ACh)-induced endothelium-dependent relaxation and cGMP response in NTG-tolerant isolated rat aorta. Ring strips prepared from the thoracic aorta of male Wistar rats were mounted in tissue baths and contracted with 10(-6) M norepinephrine. NTG and ACh relaxation responses were compared before and after 1 h treatment with 5 x 10(-4) M NTG. The chronological changes in tissue cGMP levels by 10(-6) M NTG and ACh were compared between a control group (untreated) and NTG-tolerant group (treated with 5 x 10(-4) M NTG for 1 h). The NTG dose-response curve shifted markedly to the right, but the ACh dose-response curve shifted to the left after the induction of NTG tolerance. In the control group, both NTG and ACh elevated the tissue cGMP levels, but in the NTG-tolerant group only ACh elevated cGMP significantly. However, in the NTG-tolerant group, the cGMP increase induced by ACh was smaller than that in the control group. These results suggest that NTG tolerance does not decrease, but rather augments ACh-induced endothelium-dependent vascular smooth muscle relaxation in isolated rat aorta.