Possible relationship between histamine and nitric oxide release in the postischemic flow response following...

During the postischemic flow response (PFR), vasodilator mediators such as nitric oxide (NO) and histamine are liberated, influencing the blood flow rate at the onset of reperfusion. The possible roles of these two mediators, and the relationship between their release, were examined during segmental intestinal ischemia of different durations and subsequent reperfusion in two series of anesthetized dogs. In series I (untreated ischemia), 15, 30, 60, and 120 min ischemia and 2 h reperfusion were studied. In series II, the same experimental protocol was repeated after pretreatment with the NO synthase inhibitor N-nitro-L-arginine (NNA, 10 mumol/kg, i.e., 2.19 mg/kg). Intramucosal pH (pHi), segmental blood flow and effluent histamine levels were measured, and segmental vascular resistance (SVR) and PFR volumes were calculated. The ischemic periods caused a considerable fall in pHi. Reperfusion resulted in an early return to normal pHi levels following a 15 or 30 min ischemia, but this process took longer after longer occlusions. In the later phase of reperfusion, SVR was elevated. The PFR volume increased in proportion to the duration of occlusion, except after the 120 min ischemia. At the onset of reperfusion, peak histamine levels rose in parallel with the duration of ischemia. During reperfusion, a prolonged decrease in pHi, an increase in SVR, and a reduction in PFR volume, with no significant histamine level elevation, were observed in the NNA-treated groups. This study indicates that both NO and histamine take part in the PFR in the canine small intestine. Inhibition of NO synthesis prevents the postischemic release of histamine.