Protein synthesis in pulmonary arteries from rats exposed to hyperoxia.

These studies were undertaken to determine the relationship of early changes in the synthesis rates and contents of collagen, elastin, and soluble tissue protein of pulmonary arteries in rats exposed chronically to normobaric hyperoxia. The growth response of pulmonary arteries was characterized by proportionate increases in the contents of the three protein fractions after 7 days (130% of control) and 21 days (194% of control) of exposure. Fractional rates of protein synthesis were assessed both in vivo and in vitro with the use of several radiolabeled amino acids as tracers to minimize uncertainties of the relationships of the specific radioactivities of measured amino acid pools and the precursors for the proteins fractions. Values for fractional synthesis rates of collagen, elastin, and soluble protein in vitro in pulmonary arteries isolated from control rats were 2.2, 1.6, and 19%/day, respectively. Rates of synthesis of collagen and soluble protein in vitro were approximately 20% lower than that determined in control rats in vivo. The fractional synthesis rates of the three protein fractions in isolated arteries from experimental rats were unchanged after 1 day of hyperoxic exposure, decreased marginally after 3 days, and markedly increased after 7 days. At this time the absolute increments in the fractional synthesis rates of collagen (+4.7%/day) and elastin (+5.0%/day) were less than that of soluble tissue protein (+16%/day) and were more comparable to the accumulation rate of proteins in the tissue. The disproportionate increment in the fractional rate of soluble protein synthesis suggests that the fractional rate of degradation of soluble protein was also increased during the growth response in this model of hypertension.

Referral patterns and exercise response in the rehabilitation of female coronary patients aged greater than or equal to 62 years.

Gender-related differences in cardiac rehabilitation referral patterns and response to an aerobic conditioning program were examined in 226 hospitalized older coronary patients (aged greater than or equal to 62 years). Overall, the outpatient cardiac rehabilitation participation rate in this population was 21%. Older women were less likely to enter cardiac rehabilitation than were older men (15 vs 25%; p = 0.06), despite similar clinical profiles. This was explained primarily by a greater likelihood of primary physicians to strongly recommend cardiac rehabilitation to men. Before conditioning, women who entered cardiac rehabilitation were less fit than were men; peak oxygen consumption was 18% lower in women (16 +/- 5 vs 20 +/- 5 ml/kg/min; p = 0.02). However, both groups improved aerobic capacity similarly in response to a 12-week aerobic conditioning program, with maximal oxygen consumption increasing by 17% in women and by 19% in men. Thus, older female coronary patients are less likely to be referred for cardiac rehabilitation, despite a similar clinical profile and improvement in functional capacity from the training component.

Localization of collagen in the rat lung: biochemical quantitation of types I and III collagen in small airways, vessels, and parenchyma.

The marked insolubility of pulmonary collagen has limited its accurate biochemical quantitation in small samples of lung and other tissues. We have recently developed a microassay based on radioisotope dilution techniques that we have used for the accurate determination of types I and III collagen in extremely small tissue samples. By applying this method to carefully dissected small airways and vessels and samples of parenchymal tissue of rat lungs, we have localized and quantitated biochemically the type I and III structural collagens of the lung. Large pulmonary arteries are the units richest in these interstitial collagen types on the basis of dried tissue weight (50 micrograms/100 micrograms dried tissue). Amounts of both types I and III collagen are considerably lower in the alveolar domain than in vessels and airways of the rat lung. The proportion of tissue composed of these collagen types decreases centripetally in rat pulmonary arteries, but increases in the bronchial tree. The relative proportions of type I and type III remain constant in all the structures tested. The higher total amount of collagen in the nonalveolar domain has implications for biochemical studies based on whole lung samples.

Altered artery mechanics and structure in monocrotaline pulmonary hypertension.

Pulmonary hypertension in rats, induced by an injection of monocrotaline, is associated with changes in the wall structure of the pulmonary arterial bed. We have studied the effects of this remodeling on mechanical properties of cylindrical pulmonary artery segments from rats 21 days after monocrotaline (MCT) injection. Resting and active (KCl induced) circumference-tension relationships were established for segments of extrapulmonary and intrapulmonary arteries isolated from the hilum and the fifth lateral branch from the axial pathway (all preacinar). The thicknesses of the vessel wall, the media, and adventitia were measured at several positions around the circumference of the artery by computerized analysis of histological cross sections of the segments fixed at a standard circumference. Resting and active stress were also calculated. The study shows that active circumferential tension and active stress are reduced in vessels from MCT-treated rats. Based on our findings, it is unlikely that altered contractile function of preacinar arteries contributes significantly to the increased vascular resistance seen in this model.

Pharmacologic properties of isolated proximal pulmonary arteries after seven-day exposure to in vivo hyperoxia.

Marked damage to the endothelium is associated with the pulmonary hypertension that develops during in vivo exposure to hyperoxia at normobaric pressures. We hypothesized that endothelial cell damage may contribute to initial increases in vascular tone during the development of hypertension by altering the metabolism of vasoactive compounds and/or modulating vessel responses to those agents that require an intact endothelium for their actions. This study reports the effects of in vivo hyperoxic damage to the lung on the pharmacologic properties of isolated pulmonary vessels. Proximal pulmonary arteries isolated from adult and weanling rats that breathed 85% O2 for 7 days were studied using myograph techniques. Isometric tension development was recorded in response to the cumulative addition of prostaglandin F2 alpha (PGF2 alpha) and the ability of acetylcholine (ACh) to relax precontracted vessels was subsequently assessed. Sensitivities to PGF2 alpha were increased in both adult and weanling hyperoxic vessels relative to control. Conversely, relaxation to acetylcholine was reduced following hyperoxic injury. Control vessels relaxed completely to acetylcholine addition, while only a 30% relaxation was recorded in adult hyperoxic arteries and a 50% relaxation was measured in weanling hyperoxic tissues. This effect on vasodilation was specific for the endothelium-dependent dilator ACh. By contrast, relaxation responses to sodium nitroprusside and papaverine, endothelium-independent agonists, were unaffected following hyperoxic injury. These results demonstrate that in vivo exposure to high O2 concentrations increases the sensitivity of isolated pulmonary arteries to the vasoconstrictor PGF2 alpha and markedly diminishes the ability of ACh to relax precontracted pulmonary vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Proliferative changes in the pulmonary arterial wall during short-term hyperoxic injury to the lung.

Injury to the lung during in vivo exposure to hyperoxia results in vascular restructuring and pulmonary hypertension. This study reports the pattern of cellular proliferation that occurs in proximal intrapulmonary arteries over time during vessel wall injury and adaptation to increased partial pressures of oxygen. Although the remodeling of the capillary bed has been emphasized particularly during oxygen injury to the lung, this report identifies significant proliferative changes within the vessel wall of proximal arterial segments isolated from rats exposed to 85% oxygen. An increased incorporation of 3H-thymidine by endothelial cells is the earliest and most dramatic vessel wall response. The labeling index of these cells is increased more than tenfold by the end of 7 days in hyperoxia. Proliferation of medial smooth muscle cells and adventitial fibroblasts is also significantly increased. The increased cell number within these compartments is noted especially for its contribution to the overall vessel wall hypertrophy observed in chronic hyperoxic pulmonary hypertension. This general proliferative response is accompanied by specific shifts in the relative percentages of different actin protein isoforms as identified by two-dimensional gel electrophoresis. Changes in the distribution of actin isoforms are discussed as potential markers of a phenotypic modulation among vascular smooth muscle cells that occurs during the progression of pulmonary vessel wall remodeling.

Mechanical properties and structure of isolated pulmonary arteries remodeled by chronic hyperoxia.

Normobaric hyperoxia is known to cause pulmonary hypertension with major restructuring of the walls of large and small pulmonary arteries. This study reports the effects of 21 days of exposure to 87% oxygen on the resting and active mechanical properties and structure of pulmonary arterial segments. Segments from the hilar region, extrapulmonary and proximal preacinar, and selected distal preacinar regions were studied. Resting and active (KCl-induced) tension:circumference curves were determined for each vessel. Morphometric measures were made of vessels fixed at a standard circumference using computerized planimetry. The areas of the media and adventitia as well as vessel wall thickness were increased in hyperoxic vessels. The walls of segments from the hypertensive rats demonstrated an increased stiffness based upon analysis of vessel resting tension:circumference relationships while the tangent modulus (a measure of stiffness normalized to tissue dimensions) was unchanged. Paradoxically, despite medial hypertrophy in the pulmonary vessels remodeled by hyperoxia, active tension was reduced. This study reveals that the resulting hypertensive state is not readily explained by an inherent increase in the maximal contractile capabilities of the remodeled vessel. Rather, obliteration of vessels in combination with increased resting stiffness appear to be the basis for pulmonary hypertension induced in hyperoxia.