Excess collagen in hypertensive pulmonary arteries decreases vascular distensibility.

Abstract

Increased vascular collagen content is a major feature of pulmonary vascular remodeling. The functional role of excess collagen in decreasing pulmonary vascular compliance has not been established. We determined whether there was a correlation between hydroxyproline content of rat pulmonary artery segments and elastance (EPA) of the pulmonary artery bed during development of hypoxic pulmonary hypertension (10% O2, 10 d) and normoxic recovery. EPA was measured by air-filled pressure-volume curves. After 10 d of hypoxia, hydroxyproline content increased approximately 2-fold in large segments (1,200-250 microns in diameter) but not significantly in small segments (> 250 microns). Elastance increased from 87 +/- 6 (SEM) to 145 +/- 8 mm Hg/ml (p < 0.05) within 5 d of hypoxia and returned to control value 3 wk after recovery. There was a correlation between collagen content and EPA in large segments during development of hypertension; no correlation was found during recovery from hypoxia. The ratio of hydroxyproline to total protein was unchanged in large segments after recovery from hypoxia but was increased in small segments after recovery. We conclude that increased collagen in large pulmonary arteries directly influences EPA during the development of hypoxic pulmonary hypertension.

The role of collagen in extralobar pulmonary artery stiffening in response to hypoxia-induced pulmonary hypertension

“…6A). In previous studies on mice (20,21), rats (4,42), and calves (23), chronic hypoxia has been found to increase elastic modulus. In some of these studies, modulus in a low-strain range was calculated (20,23), and in these cases chronic hypoxia increased the modulus.…”

“…In PA segments from rats, the elastance (slope of the pressure-volume relationship) (42) and wall stress (27) have previously been found to return to normal with recovery from hypoxia. As predicted, PA stretch and E 2 did not return to normal levels in Col1a1 R/R mice.…”

“…biomechanics; mechanobiology; elastin; hydroxyproline; recovery HYPOXIC PULMONARY HYPERTENSION (HPH) is caused by living at high altitudes and is a complication of many lung diseases, including chronic obstructive pulmonary disease (1, 13, 16), cystic fibrosis (10), and obstructive sleep apnea (13), which contributes significantly to morbidity and mortality. Pulmonary vascular remodeling due to chronic HPH increases conduit pulmonary artery (PA) stiffness (4,20,21,23,34,42). Conduit PA stiffening likely increases wave reflections to impair right ventricular systolic function, much like aortic stiffening impairs left ventricular systolic function (18,29,33).…”

“…Pulmonary vascular remodeling due to chronic HPH increases conduit pulmonary artery (PA) stiffness (4,20,21,23,34,42). Conduit PA stiffening likely increases wave reflections to impair right ventricular systolic function, much like aortic stiffening impairs left ventricular systolic function (18,29,33).…”

“…Stiffening of the extralobar PAs has been shown to be linked with accumulation of collagen and elastin (4,20,21,23,42). Previous attempts to understand the individual roles of collagen and elastin in arterial mechanical function have focused on correlative relationships during HPH progression (20,21) or ex vivo degradation of one component before mechanical testing (23).…”