Possible mechanism(s) for permeability recovery of venules during histamine application.

Histamine is known to cause a substantial increase in the permeability of venules to both water and proteins. However, this increase is transient, i.e., the initially elevated permeability returns toward control levels, or "recovers," even during continuous histamine stimulation. In this investigation, we attempted to identify the possible chemical signal(s) initiating the permeability recovery process in single venules of rat mesentery. Specifically, we tested whether histamine's binding to H2 receptors and/or the production of prostacyclin by endothelial cells was involved in this process. To achieve this aim, the time course of endothelial cells was involved in this process. To achieve this aim, the time course of histamine-induced changes in permeability to alpha-lactalbumin was measured in the presence of H2 receptor antagonist (cimetidine) or of prostacyclin synthetase inhibitor (tranylcypromine), respectively. Permeability of individually perfused microvessels was measured using fluorescence microscopy. The results demonstrated that permeability recovery was not affected by the H2 receptor antagonist but was suppressed or even abolished by the prostacyclin synthesis inhibitor. Therefore, these results suggest that the production of prostacyclin by endothelial cells might serve as one chemical signal to initiate the permeability recovery process, whereas histamine's binding to H2 receptors is not involved in this phenomenon.