Influence of perfusate PO2 on hypoxic pulmonary vasoconstriction in rats.

Abstract

The purpose of these studies was to evaluate the influence of perfusate oxygen tension on hypoxic pulmonary vasoconstriction and to identify the site at which both alveolar and perfusate gas tensions stimulate hypoxic pulmonary vasoconstriction. Lungs from adult rats were ventilated and perfused in vitro at constant temperature, PCO2, and pH, with a perfusion circuit incorporating a membrane oxygenator that allowed independent control of the alveolar and perfusate gas tensions. Blood flow to the lung was constant (0.06 ml per g body weight per min), and pulmonary vascular resistance was therefore proportional to pulmonary artery pressure. In study 1, the pulmonary artery pressor response to zero or 22 mm Hg alveolar oxygen was measured when the perfusate oxygen tensions were approximately 8, 26, 41, 64, or 128 mm Hg. The pressor response as a percent of the maximum pressure change was progressively reduced as perfusate oxygen tension increased. For alveolar oxygen tension of zero; the pressor response = 128 -39 (Log PPO2) and r = 0.8 (P less than 0.01), the effect of perfusate gas tension on the response to alveolar gas tension of 22 mm Hg was similar. These results demonstrate that the stimulus for hypoxic pulmonary vasoconstriction is a function of both alveolar and perfusate oxygen tension. In study 2, the response to alveolar oxygen tension of 42 mm Hg was measured with mean perfusate oxygen tensions of 130, 52, and 17 mm Hg. In six animals with forward perfusion, the responses decreased with increasing perfusate oxygen tension, as in study 1. In another six animals, with retrograde perfusion, the responses to alveolar hypoxia were not altered when perfusate oxygen tension was increased. These results demonstrate that the sensor region for hypoxic pulmonary vasoconstriction is precapillary. These studies confirm and extend previous hypotheses that alveolar and perfusate oxygen tensions together, determine the PO2 at a precapillary site to stimulate hypoxic pulmonary vasoconstriction.

Hypoxic Pulmonary Vasoconstriction

“…Indeed, changing one independently of the other in ventilated lungs (142, 753,826,841,1197,1199,1487) or changing P mv O 2 in atelectatic lungs (424) altered pulmonary vasomotor tone. Quantification of these effects allowed estimation of P s O 2 as a weighted average of alveolar and mixed venous PO 2 ; e.g., for the dog, P s O 2 ϭ P A O 2 0.62 ϩ P mv O 2 0.38 (1190,1197).…”

Oxygen sensing and signal transduction in hypoxic pulmonary vasoconstriction

“…Some decades ago, it became clear that HPV is primarily achieved by vasoconstriction of the pre-capillary pulmonary vessels, located at the entrance of the acinus, and to a lesser degree by post-capillary-located venules [21][22][23][24]. These vessels respond mainly to alveolar hypoxia, as well as to a drop in pulmonary arterial oxygen tension (PO 2 ) [25], but not to changes in pulmonary venous PO 2 [26]. When pre-capillary vessels are isolated and endothelium denuded, they constrict in the presence of hypoxia, suggesting that the sensor and effector mechanisms of HPV are located in these vessels [27].…”

The pathogenesis of lung injury following pulmonary resection

“…Such hypoxic pulmonary vasoconstriction (HPV) occurs principally at the arteriolar level, although (a lesser degree of venoconstriction has also been identified [15]. The mechanisms underlying the reflex are not entirely understood, but it has long been recognized that the endothelium plays a role in modulating HPV by releasing a variety of vasoactive substances including the vasodilators prostacyclin and nitric oxide, and vasoconstrictor endothelins (ETs).…”