Pressure is proinflammatory in lung venular capillaries

Endothelial responses may contribute importantly to the pathology of high v ascular pressure. In lung venular capillaries, we determined endothelial [C a2+](i) by the fura-2 ratioing method and fusion pore formation by quantify ing the fluorescence of FM1-43. Pressure elevation increased endothelial [C a2+](i). Concomitantly evoked exocytotic events were evident in a novel spa tial-temporal pattern of fusion pore formation. Fusion pores formed predomi nantly at vascular branch points and colocalized with the expression of P-s electin. Blockade of mechanogated Ca2+ channels inhibited these responses, identifying entry of external Ca2+ as the critical triggering mechanism. Th ese endothelial responses point to a proinflammatory effect of high vascula r pressure that may be relevant in the pathogenesis of pressure-induced lun g disease.