EFFECT OF CAPSAICIN AND RESINIFERATOXIN ON GASTROINTESTINAL BLOOD-FLOW IN RATS

The effect of capsaicin and resiniferatoxin on gastrointestinal blood flow was studied in anaesthetized rats by laser Doppler flowmetry. Res iniferatoxin injected into the jugular vein (0.08-1.6 nmol/kg) produce d a marked and dose-dependent increase in gastric blood flow, while th e effect of capsaicin (0.33-19.6 nmol/kg) was transient, variable and accompanied by profound systemic blood pressure changes. After acute b ilateral cervical vagotomy combined with sympathetic neurone blockade (guanethidine 16 mu mol/kg) or alpha-adrenoceptor blockade (phentolami ne 1.6 mu mol/kg), the vasodilator response to injected resiniferatoxi n was more pronounced, indicating that the resiniferatoxin-induced gas tric vasodilatation is not due to reflexes via parasympathetic or symp athetic efferent fibers. Resiniferatoxin given i.v. (0.08-0.64 nmol/kg ) evoked a similar increase in the blood flow of the jejunum. Capsaici n (0.33-33 mu M) or resiniferatoxin (0.16-1.6 mu M) applied topically to the serosal surface of the stomach or jejunum produced a pronounced and long-lasting increase in blood flow after vagotomy and guanethidi ne treatment. The blood flow and blood pressure responses to capsaicin and resiniferatoxin were absent in rats desensitized with systemic ca psaicin pretreatment. These laser Doppler data provide the first evide nce for the effect of resiniferatoxin on gastrointestinal microcircula tion and indicate the advantages of this agent and technique to study the sensory-efferent function of capsaicin-sensitive fibres.