Nicotine enhances angiotensin II-induced mitogenic response in vascular smooth muscle cells and fibroblasts.

Abstract

OBJECTIVE:

The pathogenetic mechanism of tobacco-related cardiovascular diseases is still not well defined. We examined the potential possibility of an interaction between nicotine, a major component of cigarette smoke, and angiotensin II (Ang II), which plays an important role in the pathogenesis of cardiovascular diseases characterized by Ang II type 1 (AT1) receptor-mediated abnormal growth of vascular smooth muscle cells (VSMC) and fibroblasts.

METHODS AND RESULTS:

Nicotine or Ang II-stimulated [3H]thymidine incorporation and c-fos expression in adult rat aortic VSMC and adventitial fibroblast. The nicotine-induced DNA synthesis was not affected by valsartan, an AT1 receptor-specific blocker, or PD123319, an Ang II type 2 (AT2) receptor-specific antagonist. Nicotine or Ang II stimulation rapidly increased extracellular signal-regulated kinase (ERK) activation, tyrosine- and serine-phosphorylation of signal transducer and activator of transcription (STAT)1 and STAT3, and p38 mitogen-activated protein kinase (p38 MAPK), in both cell types. Interestingly, co-administration of nicotine and Ang II at lower doses, which did not affect cell growth, induced DNA synthesis and c-fos expression accompanied by enhancement of ERK, STAT, and p38MAPK activity. PD98059, a mitogen-activated protein kinase/ERK kinase inhibitor, or SB23058, a p38MAPK inhibitor, significantly attenuated the vasotrophic effect of nicotine and Ang II.

CONCLUSIONS:

These results suggest that nicotine exerts a growth-promoting effect on vascular cells and enhances the Ang II-induced vasotrophic effect, which is at least partly mediated by the activation of ERK, STAT, and p38MAPK.

• Authors: Jian-Mei Li, Tai-Xing Cui, Tetsuya Shiuchi, Hong-Wei Liu, Li-Juan Min, Midori Okumura, Toyohisa Jinno, Lan Wu, Masaru Iwai, Masatsugu Horiuchi
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 24 Issue 1 Pg. 80-4 (Jan 2004) ISSN: 1524-4636 [Electronic] United States
• PMID: 14592853 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II
• Nicotine

Topics

• Angiotensin II (pharmacology)
• Animals
• Aorta, Thoracic (cytology)
• DNA Replication (drug effects)
• Dose-Response Relationship, Drug
• Drug Synergism
• Fibroblasts (drug effects, metabolism)
• Genes, Reporter
• Genes, fos
• MAP Kinase Signaling System (drug effects)
• Mitosis (drug effects)
• Muscle, Smooth, Vascular (cytology, drug effects, metabolism)
• Nicotine (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Transfection