Increased histamine and 5-HT in portal vein plasma and mesenteric lymph during brief ischemia and reperfusion

Brief mesenteric ischemia (10 min) can stimulate both visceral A delta- and C-fiber afferents and evoke reflex excitation of the cardiovascular system. We have shown that exogenous histamine causes reflex cardiovascular responses and that intra-arterial injection of 5-hydroxytryptamine (5- HT) into a mesenteric artery stimulates visceral A delta- and C-fiber afferents. We therefore hypothesized that brief abdominal ischemia is associated with release of histamine and 5-HT into the interstitium, where these mediators could stimulate or sensitize ischemically sensitive visceral afferent nerve endings. Accordingly, we measured concentrations of histamine and 5-HT in portal venous blood plasma and intestinal lymph fluid in cats. Cannulas were placed in a portal vein and in an intestinal lymphatic duct distal to the lymph node. Lymph and plasma histamine and 5-HT concentrations were measured by high-performance liquid chromatography before, during, and immediately after 10-min occlusion of the descending thoracic aorta. Histamine concentration increased significantly (P < 0.01) in portal venous blood plasma from a preocclusion level of 2.2 +/- 0.6 to 4.6 +/- 1.0 and 6.4 +/- 1.3 nmol/ml and in lymph fluid from a preocclusion level of 3.4 +/- 1.0 to 6.3 +/- 1.3 and 6.4 +/- 1.3 nmol/ml (n = 18) during brief ischemia and reperfusion, respectively. Also, the 5-HT concentration was significantly (P < 0.01) elevated in portal venous blood plasma from a preocclusion concentration of 1.1 +/- 0.5 to 2.7 +/- 0.8 and 2.5 +/- 0.8 nmol/ml and in lymph from a preocclusion level of 1.8 +/- 0.7 to 4.0 +/- 1.4 and 4.6 +/- 1.3 nmol/ml (n = 13) during brief ischemia and reperfusion, respectively. Because visceral afferent nerve endings are located in the interstitium, elevation of the interstitial concentration of histamine and 5-HT may contribute to the stimulation or sensitization of these nerve terminals during the brief ischemia and reperfusion period.