Differential effect of nitric oxide synthase inhibition on sigmoid colon longitudinal and circular muscle responses to nicotine and nerve stimulation in vitro

Author:

McKirdy H C1,Richardson C E2,Green J T2,Rhodes J2,Williams G T3,Marshall R W4

Affiliation:

1. Department of Surgery, Therapeutics and Toxicology, University of Wales College of Medicine, Cardiff, UK

2. Department of Gastroenterology, Therapeutics and Toxicology, University of Wales College of Medicine, Cardiff, UK

3. Department of Pathology, and Therapeutics and Toxicology, University of Wales College of Medicine, Cardiff, UK

4. Department of Pharmacology, Therapeutics and Toxicology, University of Wales College of Medicine, Cardiff, UK

Abstract

Abstract Background Nicotine has been shown to release nitric oxide from nerves in human sigmoid colon. This effect has been used to investigate the innervation and functional relationship of the longitudinal and circular muscle layers. Methods Strips of longitudinal and circular muscle were obtained from 19 patients with colorectal cancer. The strips from ten patients were subjected to electrical field stimulation (EFS) in vitro using stimulus parameters for selective stimulation of nerves. The effect of nicotine 1–10 μmol/l on EFS responses was then measured in the presence and absence of a nitric oxide synthase inhibitor, nitro-l-arginine methyl ester (l-NAME) 200 μmol/l. The effect of nicotine on spontaneous activity was investigated in the muscle strips from the other nine patients. Results Both longitudinal and circular strips responded to EFS with contraction. The time to achieve a peak contractile response (time to peak; TTP) was significantly longer (P < 0·001) in circular strips. l-NAME reduced the mean(s.e.m.) TTP in circular muscle from 23·3(2·0) to 17·2(1·5) s (P = 0·007) and altered its pattern of response to resemble that of longitudinal muscle. Nicotine 10 μmol/l reduced the contraction to EFS in circular (P < 0·001) but not in longitudinal (P = 0·347) muscle. The nicotine-induced reduction in circular muscle contraction was blocked by l-NAME 200 μmol/l (P = 0·005). Conclusion These findings suggest that nitric oxide release on neural stimulation is greater in circular than in longitudinal muscle.

Publisher

Oxford University Press (OUP)

Subject

Surgery

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