REGULATION OF NATRIURETIC PEPTIDE RECEPTOR-A AND RECEPTOR-B EXPRESSION BY TRANSFORMING GROWTH FACTOR-BETA(1) IN CULTURED AORTIC SMOOTH-MUSCLE CELLS

被引:40
作者
FUJIO, N [1 ]
GOSSARD, F [1 ]
BAYARD, F [1 ]
TREMBLAY, J [1 ]
机构
[1] UNIV MONTREAL,HOTEL DIEU,CTR RECH,CELLULAR BIOL HYPERTENS LAB,MONTREAL H2W 1T8,PQ,CANADA
关键词
RECEPTORS; ATRIAL NATRIURETIC PEPTIDE; TRANSFORMING GROWTH FACTOR BETA; MUSCLE; SMOOTH; VASCULAR; CYCLIC GUANOSINE MONOPHOSPHATE; HYPERTENSION; ESSENTIAL;
D O I
10.1161/01.HYP.23.6.908
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Two types of natriuretic peptide receptors (NPR-A and NPR-B) are membrane guanylate cyclases whose relative expression varies in different tissues. Because natriuretic peptides have been shown to inhibit aortic smooth muscle proliferation, we investigated the regulation of NPR-A and NPR-B in these cells under different proliferative conditions. NPR subtype mRNA levels were measured by our newly developed quantitative reverse transcription-polymerase chain reaction assay using mutated NPR-A and NPR-B cRNA as internal standards. The functional impact of their expression was determined by atrial nutriuretic peptide (ANP)- and C-type natriuretic peptide (CNP)-induced stimulation of cyclic GMP production. In the intact aorta, NPR-B mRNA levels were found to be 10-fold higher than those of NPR-A, This dominance was further amplified (1000-fold) in long-term cultures (10 to 15 passages) of aortic smooth muscle cells (ASMC). Higher cyclic GMP production with CNP than with ANP was observed in cultured ASMC from Wistar-Kyoto (WKY) rats. Similar stimulation by the two agonists was noted in spontaneously hypertensive rat (SHR) cells, paralleled by a 10-fold increase in NPR-A mRNA levels and ANP stimulation of cyclic GMP in hypertensive cells. The present study also evaluated NPR-A and NPR-B mRNA control by transforming growth factor-beta(1) (TGF-beta(1)), an important regulator of cell proliferation that is overexpressed in SHR ASMC. TGF-beta(1) decreased both NPR-A and NPR-B mRNA levels with a predominant effect in SHR cells at high cell density. This effect was paralleled by a fall in CNP- and ANP-induced cyclic GMP levels after preincubation with TGF-beta(1). Our study demonstrates the increase of NPR-B expression from contractile to proliferative phenotypes of ASMC and presents the first evidence of cytokine regulation of the two NPR subtypes at the mRNA level with the potential for an integrated role of these two systems in the control of vascular smooth muscle growth.
引用
收藏
页码:908 / 913
页数:6
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