Brief mesenteric ischemia increases PGE2, but not PGI2, in intestinal lymph of cats

Mesenteric ischemia of short duration (5-10 min) can stimulate Aδ- and C- fiber afferent nerve endings in the viscera to reflexly activate the cardiovascular system. The mechanism of activation of abdominal visceral afferents is probably multifactorial and may involve prostaglandins (PGs), which have been shown to directly stimulate and/or sensitize visceral afferents when administered exogenously. We hypothesized that brief visceral ischemia is accompanied by release of PGI₂ and PGE₂ into the interstitium, where these cyclooxygenase products could stimulate or sensitize visceral afferent nerve endings. Accordingly, we measured immunoreactive PGE₂ (iPGE₂) and 6-keto-PGF(1α) (i6-keto-PGF(1α), the stable metabolite of PGI₂, in lymph draining the ischemic viscera as well as in portal venous blood. An intestinal lymph duct distal to the lymph node was cannulated in pentobarbital sodium-anesthetized cats. Lymph and plasma iPGE₂ and i6-keto- PGF(1α) concentrations were measured by radioimmunoassay before, during, and immediately after a 5- to 10-min occlusion of the descending aorta. The i6- keto-PGF(1α) concentration increased significantly (P < 0.001) in portal venous plasma (61 ± 12 to 107 ± 18 pg/0.1 ml; n = 14) but not in lymph (148 ± 30 to 159 ± 24 pg/0.1 ml; n = 16). In contrast, iPGE₂ concentration was significantly (P < 0.01) elevated in both venous plasma (156 ± 16 to 207 ± 26 pg/0.1 ml; n = 19) and lymph (520 ± 48 to 590 ± 52 pg/0.1 ml; n = 20). The increase in PGI₂ concentration in venous plasma but not in lymph suggests that there is endothelial release of PGI₂ into the circulation during ischemia and that this prostanoid may not play an important role in stimulating nerve endings located in the interstitium. An ischemia-induced elevation of interstitial PGE₂ concentration, however, suggests that this PG is an important factor in the stimulation of visceral afferents during brief ischemia.