In:
American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 283, No. 1 ( 2002-07-01), p. L42-L51
Abstract:
We examined gene and surface expression and activity of the endothelin (ET)-1 receptors (ET A and ET B ) in subendothelial (L1) and inner medial (L2) cells from the main pulmonary artery of sheep with continuous air embolization (CAE)-induced chronic pulmonary hypertension (CPH). According to quantitative real-time RT-PCR, basal gene expression of both receptors was significantly higher in L2 than L1 cells, and hypertensive L2 cells showed significantly higher gene expression of ET B than controls. Expression of both genes in hypertensive L1 cells was similar to controls. Fluorescence-activated cell sorter analysis confirmed the increased distribution of ET B in hypertensive L2 cells. Although only the ET A receptors in control L2 cells showed significant binding of [ 125 I]-labeled ET-1 at 1 h, both receptors bound ET-1 to hypertensive cells. Exposure to exogenous ET-1 for 18 h revealed that only the L2 cells internalized ET-1, and internalization by hypertensive L2 cells was significantly reduced when compared with controls. Treatment with ET A (BQ-610) and ET B (BQ-788) receptor antagonists demonstrated that both receptors contributed to internalization of ET-1 in control L2 cells, whereas in hypertensive cells only when both receptor antagonists were used in combination was significant suppression of ET-1 internalization found. We conclude that in sheep receiving CAE, alterations in ET B receptors in cells of the L2 layer may contribute to the maintenance of CPH via alterations in their expression, distribution, and activity.
Type of Medium:
Online Resource
ISSN:
1040-0605
,
1522-1504
DOI:
10.1152/ajplung.00337.2001
Language:
English
Publisher:
American Physiological Society
Publication Date:
2002
detail.hit.zdb_id:
1477300-4
SSG:
12
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