Altered Expression of ETB-Receptor mRNA in the Lung of Rats with Pulmonary Hypertension

Yorikane, Ryosuke; Miyauchi, Takashi; Sakai, Satoshi; Sakurai, Takeshi; Yamaguchi, Iwao; Sugishita, Yasuro; Goto, Katsutoshi

doi:10.1097/00005344-199322008-00088

Cited by 37 publications

(18 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the protein expression of the ET A receptor tended to increase in MCT rats, these results were however non-significant. ET B receptor mRNA expression was reduced by approximately 45% in PAH, confirming the results obtained from whole lung homogenates [20][21][22]. Likewise, ET B receptor protein levels were reduced.…”

Section: Discussionsupporting

confidence: 83%

Change in pharmacological effect of endothelin receptor antagonists in rats with pulmonary hypertension: Role of ETB-receptor expression levels

Sauvageau¹,

Thorin²,

Villeneuve³

et al. 2009

Pulmonary Pharmacology & Therapeutics

View full text Add to dashboard Cite

Background and purpose-The endothelin (ET) system is activated in pulmonary arterial hypertension (PAH). The therapeutic value of pharmacological blockade of ET receptors has been demonstrated in various animal models and led to the current approval and continued development of these drugs for the therapy of human PAH. However, we currently incompletely comprehend what local modifications of this system occur as a consequence of PAH, particularly in small resistance arteries, and how this could affect the pharmacological response to ET receptor antagonists with various selectivities for the receptor subtypes. Therefore, the purposes of this study were to evaluate potential modifications of the pharmacology of the ET system in rat pulmonary resistance arteries from monocrotaline (MCT)-induced pulmonary arterial hypertension.Experimental approach-ET-1 levels were quantified by ELISA. PreproET-1, ET A and ET B receptor mRNA expressions were quantified in pulmonary resistance arteries using Q-PCR, while protein expression was evaluated by Western blots. Reactivity to ET-1 of isolated pulmonary resistance arteries was measured in the presence of ET A (A-147627), ET B (A-192621) and dual ET A/B (bosentan) receptor antagonists.Key results-In rats with PAH, plasma ET-1 increased (p < 0.001) while pulmonary levels were reduced (p < 0.05). In PAH arteries, preproET-1 (p < 0.05) and ET B receptor (p < 0.001) gene expressions were reduced, as were ET B receptor protein levels (p < 0.05). ET-1 induced similar vasoconstrictions in both groups. In arteries from sham animals, neither bosentan nor the ET A or the ET B receptor antagonists modified the response. In arteries from PAH rats, however, bosentan and the ET A receptor antagonist potently reduced the maximal contraction, while bosentan also reduced sensitivity (p < 0.01).

show abstract

Section: Discussionsupporting

confidence: 83%

Change in pharmacological effect of endothelin receptor antagonists in rats with pulmonary hypertension: Role of ETB-receptor expression levels

Sauvageau¹,

Thorin²,

Villeneuve³

et al. 2009

Pulmonary Pharmacology & Therapeutics

View full text Add to dashboard Cite

show abstract

“…After 14 days of hypoxia, increased expression of both ET A and ET B was found in the distal pulmonary arteries of rats, ET A expression occurring mainly in the media and ET B in the intima; no change in expression of either receptor was found in the large muscular pulmonary arteries (39). In contrast to the hypoxic models, in monocrotaline-induced CPH, ET B receptor mRNA was shown to be decreased in the lung (46).…”

Section: Discussionmentioning

confidence: 80%

ET-1 receptor gene expression and distribution in L1 and L2 cells from hypertensive sheep pulmonary artery

Balyakina

Chen²,

Lawrence³

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

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 ETB (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.ET A receptor; ETB receptor; smooth muscle cells; pulmonary hypertension; endothelin SINCE ITS DISCOVERY 12 YEARS AGO, endothelin (ET) has been shown to contribute to a wide variety of physiological and pathophysiological processes in various systems (22). The ET family of 21 amino acid peptides exists in three distinct isoforms: ET-1, ET-2, and ET-3. It is an extremely potent vasoconstrictor resulting in slowly developing and sustained contraction. Although the endothelial cell was originally described as the source of ET-1, it is now known that several other cell types, including pulmonary vascular smooth muscle cells, synthesize this peptide (33, 36).The biological effects of ET-1 are mediated by two distinct ET receptor subtypes, ET A and ET B (1, 35). The affinity of the ET A receptor for ET-1 has been shown to be ϳ100 times that for ET-3 (ET-1 Ͼ ET-2 Ͼ ET-3), whereas the affinity of the ET B receptor is equipotent for all three isoforms of ET (34). Early reports indicated that the ET A receptor on smooth muscle was responsible for the vasoconstrictor effect of ET-1, whereas the ET B receptor on endothelial cells modulated ET-1-induced vasodilation. However, recent pharmacological studies suggest that there are two classes of ET B with cell specific effects, ET B1 on endothelial cells mediating vasodilation and ET B2 on smooth muscle cells mediating vasoconstriction (9). The ET B receptor also functions as a "clearance receptor" and is particularly important in the lung, where 50% of ET-1 is retained (22,29).ET-1 has been linked to the development of chronic pulmonary hypertension (CPH). Increased expression of the peptide has been demonstrated in endothelial cells of pulmonary arteries from patients with idiopathic and secondary forms of pulmonary hypertension (15), and arterial-to-venous ratios of ET-1 protein were found to be elevated above the normal range in patients with pulmonary hypertension (40). Several studies have linked increased expression of ET-1 to the development of hypoxia-induced CPH in rats (5, 24), and use of ET-1 receptor antagonists has been shown both to inhibit progression of the disease and to promote recovery (4,10,43).Although these studies support a central role for ET-1 in the pathogenesis of CPH, the picture is likely more complicated than first suspected, in that prepro-ET-1 (ppET-1) mRNA is...

show abstract

Section: Discussionmentioning

confidence: 92%

“…Furthermore, studies of adult models of pulmonary hypertension demonstrate increased lung expression of ET A receptor mRNA (30) and decreased ET B receptor mRNA (31). Increased production of ET-1 has also been shown in adult rat pulmonary hypertension models (31,32). We have previously shown that pulmonary hypertension due to ductus arteriosus ligation increases ET-1 production threefold, and leads to diminished ET B -mediated vasodilation and enhanced ET A -mediated vasoconstriction, suggesting that increased ET-1 and changes in its receptor activity at least in part mediate the altered reactivity in this model of pulmonary hypertension (13).…”

Section: Discussionmentioning

confidence: 99%

Prolonged endothelin A receptor blockade attenuates chronic pulmonary hypertension in the ovine fetus.

Ivy¹,

Parker²,

Ziegler³

et al. 1997

J. Clin. Invest.

117

View full text Add to dashboard Cite

show abstract

Altered Expression of ETB-Receptor mRNA in the Lung of Rats with Pulmonary Hypertension

Cited by 37 publications

References 0 publications

Change in pharmacological effect of endothelin receptor antagonists in rats with pulmonary hypertension: Role of ETB-receptor expression levels

Change in pharmacological effect of endothelin receptor antagonists in rats with pulmonary hypertension: Role of ETB-receptor expression levels

ET-1 receptor gene expression and distribution in L1 and L2 cells from hypertensive sheep pulmonary artery

Prolonged endothelin A receptor blockade attenuates chronic pulmonary hypertension in the ovine fetus.

Contact Info

Product

Resources

About