The abnormal function of the lower oesophageal sphincter in
achalasia is likely to be due to impaired nonadrenergic, noncholinergic (NANC) inhibitory input. Since recent studies in animals suggest that
nitric oxide (NO) is implicated physiologically in the inhibitory responses of the lower oesophageal sphincter, we have investigated whether the synthesis of NO is altered in the gastro-oesophageal junction of patients with
achalasia.
NO synthase activity was investigated in samples of tissue from the gastro-oesophageal junction obtained during surgery in eight patients with typical
achalasia and six non-achalasic controls who underwent oesophagectomy for reasons other than sphincter dysfunction. The
NO synthase activity was determined by the transformation of 14C-L-arginine into 14C-L-citrulline in tissue homogenates. In addition, immunohistochemical staining of the tissues was performed using a polyclonal antibody raised against a
peptide sequence of rat brain
NO synthase. Furthermore, the relaxant response to an exogenous NO donor (
sodium nitroprusside, SNP) was measured in vitro in muscle strips obtained from two patients with
achalasia and in two non-achalasic controls.
NO synthase activity was detected in each of the samples obtained from six control patients (0.59 +/- 0.21 pmol mg-1 min-1; mean +/- SE). By contrast, none of the samples obtained from the eight patients with
achalasia had any detectable
NO synthase activity. Immunohistochemical studies confirmed the presence of
NO synthase in the myenteric plexus of the gastro-oesophageal junction of control patients and its absence in
achalasia. SNP relaxed muscle strips precontracted with
bethanechol in both control samples and those from patients with
achalasia.(ABSTRACT TRUNCATED AT 250 WORDS)