Wiltz W. Wagner

Prostacyclin contributes to inhibition of hypoxic pulmonary vasoconstriction by alkalosis

The mechanism by which extracellular alkalosis inhibits hypoxic pulmonary vasoconstriction is unknown. We investigated whether the inhibition was due to intrapulmonary production of a vasodilator prostaglandin such as prostacyclin (PGI2). Hypoxic vasoconstriction in isolated salt-solution-perfused rat lungs was blunted by both hypocapnic and NaHCO3-induced alkalosis (perfusate pH increased from 7.3 to 7.7). The NaHCO3-induced alkalosis was accompanied by a significant increase in the perfusate level of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), an hydrolysis product of PGI2. Meclofenamate, an inhibitor of cyclooxygenase, counteracted both the blunting of hypoxic vasoconstriction and the increased level of 6-keto-PGF1 alpha. In intact anesthetized dogs, hypocapnic alkalosis (blood pH increased from 7.4 to 7.5) blunted hypoxic pulmonary vasoconstriction before but not after administration of meclofenamate. In separate cultures of bovine pulmonary artery endothelial and smooth muscle cells stimulated by bradykinin, the incubation medium levels of 6-keto-PGF1 alpha were increased by both hypocapnic and NaHCO3-induced alkalosis (medium pH increased from 7.4 to 7.7). These results suggest that inhibition of hypoxic pulmonary vasoconstriction by alkalosis is mediated at least partly by PGI2.

Recruitment of Pulmonary Capillaries

Recruitment of pulmonary capillaries is an important component of gas exchange reserve that is utilized during exercise to meet the demand for increased oxygen uptake. However, important gaps exist in our understanding of the way in which alterations of pulmonary hemodynamics, with the attendant redistribution of pulmonary blood flow, affect capillary recruitment. The major reason that many aspects of pulmonary microcirculatory function are poorly understood is the considerable technical difficulty in studying pulmonary micro-vessels directly. The classical direct approach of in vivo microscopy is plagued by problems with tissue movement during the cardiorespiratory cycles. Nevertheless, important information has come historically from in vivo microscopy of the lung. The directness of this approach continues to make the technique attractive today.