DMSO-Soluble Cigarette Smoke Particles Alter the Expression of Endothelin B Receptor in Rat Coronary Artery

Abstract

In coronary artery diseases, cigarette smoking is a risk factor and the endothelin system plays a key role in the pathogenesis. This study was to examine if dimethylsulfoxide-soluble smoke particles (DSP) upregulate endothelin type-B (ET_B) receptors in the coronary artery and investigate the mechanism. The isolated rat coronary arteries were organ-cultured for 24 h. The contractile response of the coronary artery was recorded by myograph. The mRNA and protein expression of the ET_B receptors was studied using quantitative real-time PCR and immunohistochemistry. Results showed that the ET_B receptor agonist, sarafotoxin 6c, induced a weak contraction in the fresh coronary artery. After culture, the contraction curve mediated by ET_B receptor was shifted towards the left with an increased E_max of 152 ± 12%. DSP of 0.2 and 0.4 µl/ml shifted the concentration-contractile curves towards the left with further increased E_max of 270 ± 26 and 280 ± 29%, respectively. The culture increased ET_B receptor mRNA and protein levels from fresh arteries, which was further enhanced by DSP. PD98059 (ERK1/2 inhibitor), wedelolactone (NF-κB inhibitor), actinomycin D or cycloheximide significantly inhibited the DSP-enhanced contraction and expression of mRNA and protein of the ET_B receptor. However, SB203580 (p38 inhibitor) further increased DSP-enhanced contraction and protein expression of the ET_B receptor. The results indicate that DSP upregulates ET_B receptors in rat coronary artery via ERK1/2 and the NF-κB pathway.

Cyclosporin A upregulates ETB receptor in vascular smooth muscle via activation of mitogen-activating protein kinases and NF-κB pathways

“…It has been suggested that MAPK (Huang et al, 2013;Uddman et al, 2003;Xu et al, 2008) signaling pathway is involved in the transcriptional upregulation of ET B receptor. The present study demonstrated that treatment with CsA increased phosphorylation of ERK1/2 and p38.…”

“…Inflammatory NF-kB signaling pathway is also involved in the transcriptional upregulation of ET B receptor (Huang et al, 2013;Xu et al, 2008;Zheng et al, 2010). Moreover, it has been reported that activation of NF-kB was depended on both ERK1/2 and p38 MAPK signaling pathways (Chen et al, 2004;Kim et al, 2008).…”

“…Although the exact roles of VSMC ET B receptor in the development of cardiovascular diseases remain elusive, upregulation of ET B receptor in VSMC has been observed in stroke (Vikman et al, 2006), coronary ischemic heart disease (Wackenfors et al, 2004), hypertension (Nilsson et al, 2008), and atherosclerotic plaque (Iwasa et al, 1999). Moreover, a growing body of evidence suggests that mitogen-activated protein kinase (MAPK) (Huang et al, 2013;Uddman et al, 2003;Xu et al, 2008) and nuclear factor-kappaB (NF-kB) (Huang et al, 2013;Xu et al, 2008;Zheng et al, 2010) signaling pathways are involved in the transcriptional upregulation of ET B receptor.…”

Minimally Modified LDL-Induced Impairment of Endothelium-Dependent Relaxation in Small Mesenteric Arteries of Mice

“…The arterial segments were given an initial tension of 1.2 mN and were left alone to adjust to this tension for 1 h. The contractile capacity of the artery was determined by exposure to a potassium-rich (63.5 m M ) Krebs solution that had the same composition as the previous solution except that NaCl was exchanged for KCl [26]. The potassium-induced contraction was used as a reference for the contractile capacity of the artery, and segments were used only if the potassium-elicited reproducible responses were >1.0 mN [27,28].…”

PM2.5 upregulates rat mesenteric arteries 5‐HT2A receptor via inflammatory‐mediated mitogen‐activated protein kinases signaling pathway

“…Many studies have demonstrated that MAPK pathways have been shown to be associated with the GPCRs upregulation in human and rat vasculatures . In addition, over expression of contractile GPCRs in arteries were observed in rats exposed to cigarette smoke in vitro and vivo . Analytical research has demonstrated that cigarette smoke contains lots of PM 2.5 .…”