Changes in pulmonary blood flow affect vascular response to chronic hypoxia in rats.

Abstract

SUMMARY. We banded the left pulmonary artery in rats to investigate, in the same animal, the effect of both increased and decreased flow on the lung vasculature and to determine how these hemodynamic states modify the structural changes produced by a 2-week exposure to hypobaric hypoxia. In unanesthetized rats, pressures were recorded from the main pulmonary artery and aorta via indwelling catheters, cardiac output was calculated by the Fick principle, and pulmonary and systemic vascular resistance estimated. Technetium-99m macroaggregated albumin was injected and radionuclide activity counted separately over the right and left lungs as a measure of flow. At postmortem, right and left ventricles of the heart were weighed and the lungs injected to permit analysis of arteriograms and morphometric assessment of structural changes in the pulmonary vascular bed. Flow in the left lung was reduced to one-fifth normal in rats with left pulmonary artery bands. In "room air" rats, pressure proximal to the left pulmonary artery band and in the right lung was slightly higher than in nonbanded controls, but not as high as in nonbanded or banded hypoxic rats. Changes in flow and pressure in both lungs of "room air" rats with left pulmonary artery bands were associated with a mild degree of extension of muscle into peripheral pulmonary arteries normally nonmuscular, medial hypertrophy of normally muscular arteries, and reduced arterial density. These three structural changes were present in both lungs of "hypoxic" rats but were much more severe. High flow in the right lungs of "hypoxic rats" with left pulmonary artery bands worsened only the degree of extension. Decreased flow and pressure in the left lungs of these animals prevented both the extension and the medial hypertrophy of hypoxia, but not the severe reduction in arterial density. It seems that the latter may occur as a direct response to low oxygen tension, whereas extension and medial hypertrophy are influenced by altered flow and pressure, respectively. (Circ Res 52: 432-441, 1983) IN previous studies, we observed that rats, during a 2-week exposure to chronic hypoxia, develop a progressive rise in pulmonary artery pressure associated with structural changes in the pulmonary vascular bed (Rabinovitch et al., 1979). The structural changes consist of extension of muscle into peripheral arteries normally nonmuscular, increased medial wall thickness of normally muscular arteries, and reduced arterial density relative to alveolar. In the present study, we banded the left pulmonary artery in the rat to determine for the first time in the same animal how increased flow (to the right pulmonary vascular bed) and decreased flow (to the left) might alter the structural remodeling of chronic hypoxia. Methods Animals StudiedTwenty-four adult male Sprague-Dawley rats (mean weight 336 ± 33 g) were used; 15 were selected randomly to be kept in room air (room air rats) and 11 to be exposed to chronic hypobaric hypoxia (air at 380 torr) for 2 weeks (hypoxia rats). Seven of the 15 ro...

Pulmonary Toxicity of Monocrotaline Differs at Critical Periods of Lung Development

“…Yet there is no evidence of regression of extension of muscle. w e can only speculate that this is because increase in peripheral vessels produces an increase in flow which maintains extension (20).…”

High-altitude pulmonary hypertension: a pathophysiological entity to different diseases

“…In rats exposed to hypoxia, precapillary vessels of a diameter of y25 mm, which normally do not have smooth muscle cells, begin to generate from adventitial fibroblasts within 24 h [39]. Light microscopic examination of nonmuscular arterioles after exposure to hypoxia show that smooth muscle began to appear by day 2 at simulated altitude, the proportion of muscularised arterioles increasing along with increasing PAP [40,41]. Interestingly, all these studies show that after return to normoxia, smooth muscle cells persisted in normally nonmuscularised arterioles, suggesting that smooth muscle cells may remain for a very long time after chronic exposure to hypoxia.…”

“…It is reasonable to assume that the initial stimulus leading to excessively elevated PAP is not different from HAPE. Since remodelling of the small weekly muscularised and nonmuscular pulmonary vessels may start within hours of exposure to hypoxia [39][40][41], it is conceivable that gradual ascent to high altitude may lead to a more homogeneous distribution of hypoxic pulmonary vasoconstriction, hence a better protection of the pulmonary capillaries from elevated pressure and high flow. However, thickening of the pulmonary artery media increases pulmonary vascular resistance, which in turn cause PAP to increase and the right ventricle to fail.…”

High-altitude pulmonary hypertension: Table. 1—

“…In rats exposed to hypoxia, pre-capillary vessels of a diameter of ,25 mm, which normally do not have smooth muscle cells, begin to generate from adventitial fibroblasts within 24 h [20]. Light microscopic examination of non-muscular arterioles after exposure to hypoxia shows that smooth muscle begins to appear by day 2 at simulated altitude, with the proportion of muscularised arterioles corresponding to the increasing Ppa [21,22]. Interestingly, these previous studies show that after returning to normoxia, smooth muscle cells persisted in normally nonmuscularised arterioles, suggesting that the histological changes may persist for a very long time after chronic exposure to hypoxia.…”