Substance P mediates a gastrointestinal thermoreflex in rats

We have characterized a viscerocirculatory thermoreflex, quantified its responses, and identified the major neurotransmitter. Application of fluid at 45 °C to mucosas or serosas of the stomach, jejunum, or ileum of anesthetized rats promptly evoked consistent cardiovascular responses, namely arterial hypotension, tachycardia, and a diminished intestinal blood flow (latency ≤5 s with a duration of 2–4 min). Thus, for example, warming of the stomach caused blood pressure to decrease 40%, heart rate to increase 15%, and mesenteric blood flow to decline 50%. These responses were inhibited totally or mostly by capsaicin, administered neonatally, topically, or perineurally, by topical lidocaine, and by parenteral administration of substance P antiserum, somatostatin, or hexamethonium. Epidural anesthesia also inhibited the cardiovascular responses to visceral warming. Pretreatment with reserpine or splanchnic ganglionectomy converted the thermally induced decline in mesenteric blood flow into a vasodilator response, which could then be blocked by an antiserum to substance P. Visceral warming also stimulated afferent, preganglionic sympathetic neural activity. Our conclusions are (a) application of fluid at 45 °C to gastrointestinal organs of anesthetized rats initiates a viscerocirculatory reflex that involves primary sensory, afferent C fibers; (b) the major neurotransmitter of this reflex appears to be substance P; and (c) visceral afferent C fibers have central and peripheral vasomotor functions.