CAPSAICIN-SENSITIVE NERVES MODULATE RESTING BLOOD-FLOW AND VASCULAR TONE IN RAT GUT

Acute and chronic treatments with capsaicin were used to evaluate the role of afferent neurons in the regulation of intestinal blood flow. Experiments were performed on anesthetized rats, in which mean intestinal blood flow was determined with a pulsed Doppler flow-meter, mean systemic arterial pressure was determined with a transducer, and intenstinal vascular conductance (C) was calculated from these measurements. Acute administration of periarterial capsaicin (0.5 mg) induced biphasic intestinal vascular responses. An early hyperemic response occurred with a maximal increase in blood flow of 31% at 5 min, followed by a decrease in blood flow of 17% at 30 min. Arterial pressure was decreased by the application of capsaicin, initially by 10%. There was an early increase of 49% in conductance, followed by a 15% decrease, compared with control values. When 1 or 4 mg capsaicin was instilled into the lumen of the jejunum there was a response pattern similar to that observed after periarterial application of capsaicin. Intrajejunal capsaicin (4 mg) increased blood flow by 51%, followed by a decrease of 16%. Mean mesenteric artery conductance was increased by 32% initially and subsequently was decreased by 21%, in response to acute intrajejunal administration of capsaicin. Both mean blood flow and conductance were increased (44% and 76%, respectively) in adult rats chronically pretreated with capsaicin (170 mg total dose) when compared with vehicle-treated controls. However, in rats pretreated neonatally with capsaicin (50 mg/kg) and allowed to mature, basal flood flow was lower than in control animals but C was not different from control littermates. These findings suggest that the hyperemic effect of acute administration of capsaicin may be related to the stimulation of afferent sensory nerves and release of vasodilatory peptides. The late vasoconstrictor effect could be due to neuronal depletion of vasodilator peptides in perivascular nerves. However, changes observed in the intestinal circulation after chronic pretreatment with capsaicin in the adult rat, in contrast to the observations in the neonatally treated rat, cannot be explained entirely by simple depletion of peptides from the sensory nerves. We conclude that capsaicin-sensitive, afferent nerves in the small intestine modulate the resting vascular tone in rat gut.