Effects of natriuretic peptides on vascular smooth-muscle cells derived from different vascular beds.
1. This study explored the hypothesis that atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-natriuretic peptide (CNP) have differing antiproliferative and antihypertrophic effects on pulmonary artery (PA) and thoracic aorta (TA) smooth-muscle cells (SMCs). 2. Cultured cells were exposed to 5% fetal calf serum (FCS) and angiotensin II (A-II) to induce DNA and protein synthesis, respectively. 3. ANP (10(-7) M) significantly reduced thymidine uptake in TA by 31% +/- 2% (P < or = 0.01) but not in PA (P > or = 0.05). 4. In parallel experiments, BNP (10(-7) M) significantly reduced thymidine uptake in TA (-22% +/- 5%, P < or = 0.01), but not in PA cells (P > or = 0.05). 5. CNP (10(-7) M) did not significantly alter thymidine uptake in TA cells exposed to FCS, but it did significantly reduce uptake in PA (-28.5% +/- 4%) 2(P < or = 0.05). 6. Blunting by ANP (10(-7) M) of the A-II (10(-8) M)-induced increase in protein synthesis was significantly greater in PA than in TA cells. 7. However, BNP and CNP (10(-7) M) exerted similar antihypertrophic effects on TA and PA cells exposed to A-II. 8. The antiproliferative effects of BNP and ANP exceed those of CNP in TA SMCs, but CNP appears to be the most effective antiproliferative agent in PA SMCs. In addition, PA-derived SMCs are more sensitive to the antihypertrophic effects of ANP than TA-derived cells, suggesting phenotypic differences. The findings indicate that the natriuretic peptides may play complementary roles in modulating SMC proliferation and protein synthesis.
Arjona
A A
AA
Department of Pathology, Brown University School of Medicine, Providence, RI, USA.
Hsu
C A
CA
Wrenn
D S
DS
Hill
N S
NS
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D009419:Nerve Tissue Proteins; D011506:Proteins; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor