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EDNRA  -  endothelin receptor type A

Canis lupus familiaris

 
 
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Disease relevance of EDNRA

  • Effects of a specific endothelin-converting enzyme inhibitor on cardiac, renal, and neurohumoral functions in congestive heart failure: comparison of effects with those of endothelin A receptor antagonism [1].
  • This study supports a role of endothelin in the pathogenesis of renal insufficiency after aortic cross-clamping and demonstrates that pretreatment with the dual ETA/ETB endothelin antagonist L-754,142 preserves RBF and sodium reabsorption, leading to a significant improvement in GFR [2].
  • METHODS: We administered either the ETA receptor antagonist FR139317 (FR [n = 8], 1 and 10 mg/kg body weight) or the ETB receptor antagonist RES-701-1 (RES [n = 8], 0.2 and 1.5 mg/kg) to dogs with CHF induced by rapid ventricular pacing [3].
  • CONCLUSIONS: The results suggest that ET plays a significant role in the development of delayed cerebral vasospasm via an interaction with ETA receptors [4].
  • Furthermore, ETA receptor antagonists may represent a novel therapeutic approach to the treatment of subarachnoid hemorrhage [4].
 

High impact information on EDNRA

 

Chemical compound and disease context of EDNRA

 

Biological context of EDNRA

  • Our findings suggest that selective ETA receptor antagonists have potential therapeutic benefits affecting both hemodynamic variables and diuresis, whereas ETB receptor antagonists have adverse hemodynamic effects, with the possibility of preventing fluid retention through suppression of aldosterone secretion in dogs with CHF [3].
  • In conclusion, selective ETA receptor blockade is associated with a stimulation of the circulating renin-angiotensin system, which results from both a sensitization of pressure-dependent renin release and a larger proportion of blood pressure values falling into the low pressure range, where renin release is stimulated [14].
  • CONCLUSIONS: ET-A receptor activation mediates microvascular dysfunction through precapillary blockades and leukocyte-endothelial cell interactions after cold ischemia and reperfusion in the canine small bowel [15].
  • Independent of ET-A receptor inhibition, cardiac output during haemorrhage was maintained within the control range [16].
  • Endothelin-1 (0.1 ml, 100 nM), which has high affinity for ETA endothelin receptors, when administered to a population of right atrial neurons via their regional arterial blood supply increased neuronal activity (+173%), heart rate (+18%), as well as right (62%) and left ventricular (14%) intramyocardial systolic pressures in 12 dogs so tested [17].
 

Anatomical context of EDNRA

  • CONCLUSIONS: Endogenous ETs increase cardiac pressures and the retention of body fluid through ETA receptors in CHF [3].
  • BQ-123, an ETA receptor antagonist, had a high affinity to block the ET-1-induced IP accumulation and tracheal smooth muscle contraction with pKB values of 7.3 and 7.4, respectively [18].
  • Dynamic in vivo observation of villus microcirculation during small bowel autotransplantation: effects of endothelin-A receptor inhibition [15].
  • PURPOSE: Endothelin-1 (ET-1), a peptide produced by the vascular endothelium, causes profound renal vasoconstriction by binding to ET-A receptors [19].
  • We conclude that ischemic myocardium releases transferable vasomotor signals that produce coronary microvascular constriction during the blockade of NO production and the constrictor signal is mediated by ETA receptors [20].
 

Associations of EDNRA with chemical compounds

  • Endothelin-a receptor blockade does not debilitate the cardiovascular and hormonal adaptation to xenon or isoflurane anesthesia in dogs [21].
  • To characterize the ET receptors present in dog coronary arteries, competition binding assays with radiolabeled ET-1 using ET-1, ET-3, ETA receptor antagonist BQ-123, and sarafotoxin S6c were performed [8].
  • The nonselective ETA/ETB receptor antagonist TAK-044 inhibited the specific binding of ET-1 to the receptors in a concentration-dependent manner [22].
  • In conscious instrumented dogs, graded intracoronary (IC) doses of acetylcholine (ACh) were delivered before IC administration of Nomega-nitro-L-arginine methyl ester (L-NAME), after L-NAME, and after L-NAME plus IC bosentan, an ETA/ETB receptor blocker [23].
  • METHODS: Six dogs were studied in four protocols: (1) control experiments (controls); (2) ETA blockade using ABT-627 (ETAB); (3) AT1 blockade using losartan (AT1B); and (4) combined AT1B and ETAB (AT1B + ETAB) [24].
 

Regulatory relationships of EDNRA

 

Analytical, diagnostic and therapeutic context of EDNRA

  • Accordingly, the role of endothelin was assessed using the nonpeptidyl, dual ETA/ETB endothelin antagonist L-754,142 in a model of renal insufficiency in the anesthetized dog induced by cross-clamping the suprarenal aorta for 60 min, followed by 2 h of reperfusion [2].
  • Endothelin-A receptor antagonism improves small bowel graft perfusion and structure after ischemia and reperfusion [26].
  • Real-time quantitative PCR was used for determinations of tissue prepro-ET-1 (ppET-1), ET-1-converting enzyme (ECE-1), and ETA and ETB receptor mRNA [27].
  • INTERVENTIONS: Anesthetized mongrel dogs (ET-receptor antagonist group; n = 6) received a bolus injection of 1 mg of the nonselective ET-A/ET-B-receptor antagonist PD 145065 (Sigma Chemical; St. Louis, MO), and dogs in the control group (n = 6) received saline solution [28].
  • We investigated the expression and influence of endothelin-1, and the effects of an ETA and ETB nonselective endothelin receptor antagonist, TAK-044, at reperfusion after cold preservation in a canine lung transplantation model [29].

References

  1. Effects of a specific endothelin-converting enzyme inhibitor on cardiac, renal, and neurohumoral functions in congestive heart failure: comparison of effects with those of endothelin A receptor antagonism. Wada, A., Tsutamoto, T., Ohnishi, M., Sawaki, M., Fukai, D., Maeda, Y., Kinoshita, M. Circulation (1999) [Pubmed]
  2. Renal protection by a dual ETA/ETB endothelin antagonist, L-754,142, after aortic cross-clamping in the dog. Krause, S.M., Walsh, T.F., Greenlee, W.J., Ranaei, R., Williams, D.L., Kivlighn, S.D. J. Am. Soc. Nephrol. (1997) [Pubmed]
  3. Comparison of the effects of selective endothelin ETA and ETB receptor antagonists in congestive heart failure. Wada, A., Tsutamoto, T., Fukai, D., Ohnishi, M., Maeda, K., Hisanaga, T., Maeda, Y., Matsuda, Y., Kinoshita, M. J. Am. Coll. Cardiol. (1997) [Pubmed]
  4. Nonpeptide endothelin antagonist. Cerebrovascular characterization and effects on delayed cerebral vasospasm. Willette, R.N., Zhang, H., Mitchell, M.P., Sauermelch, C.F., Ohlstein, E.H., Sulpizio, A.C. Stroke (1994) [Pubmed]
  5. Angiotensin converting enzyme inhibition modulates endogenous endothelin in chronic canine thoracic inferior vena caval constriction. Clavell, A.L., Mattingly, M.T., Stevens, T.L., Nir, A., Wright, S., Aarhus, L.L., Heublein, D.M., Burnett, J.C. J. Clin. Invest. (1996) [Pubmed]
  6. Enhanced coronary vasoconstriction to endothelin-B-receptor activation in experimental congestive heart failure. Cannan, C.R., Burnett, J.C., Lerman, A. Circulation (1996) [Pubmed]
  7. Endothelin at pathophysiological concentrations mediates coronary vasoconstriction via the endothelin-A receptor. Cannan, C.R., Burnett, J.C., Brandt, R.R., Lerman, A. Circulation (1995) [Pubmed]
  8. Potent vasoconstriction mediated by endothelin ETB receptors in canine coronary arteries. Teerlink, J.R., Breu, V., Sprecher, U., Clozel, M., Clozel, J.P. Circ. Res. (1994) [Pubmed]
  9. Efficacy of administering an endothelin-receptor antagonist (SB209670) in ameliorating ischemia-reperfusion injury in lung allografts. Shennib, H., Lee, A.G., Kuang, J.Q., Yanagisawa, M., Ohlstein, E.H., Giaid, A. Am. J. Respir. Crit. Care Med. (1998) [Pubmed]
  10. Prevention of delayed vasospasm by an endothelin ETA receptor antagonist, BQ-123: change of ETA receptor mRNA expression in a canine subarachnoid hemorrhage model. Itoh, S., Sasaki, T., Asai, A., Kuchino, Y. J. Neurosurg. (1994) [Pubmed]
  11. A novel endothelin ETA receptor antagonist, BQ-485, and its preventive effect on experimental cerebral vasospasm in dogs. Itoh, S., Sasaki, T., Ide, K., Ishikawa, K., Nishikibe, M., Yano, M. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  12. Bosentan the mixed endothelin-A- and -B-receptor antagonist suppresses intrapericardial endothelin-1-induced ventricular arrhythmias. Horkay, F., Gellér, L., Kiss, O., Szabó, T., Vagó, H., Kékesi, V., Juhász-Nagy, A., Merkely, B. J. Cardiovasc. Pharmacol. (2000) [Pubmed]
  13. Hemodynamic effect of endothelin antagonists in dogs with myocardial infarction. Ohta, H., Suzuki, J., Akima, T., Kawai, N., Hanada, K., Nishikibe, M. J. Cardiovasc. Pharmacol. (1998) [Pubmed]
  14. Stimulation of the renin-angiotensin system by endothelin subtype A receptor blockade in conscious dogs. Berthold, H., Münter, K., Just, A., Kirchheim, H.R., Ehmke, H. Hypertension (1999) [Pubmed]
  15. Dynamic in vivo observation of villus microcirculation during small bowel autotransplantation: effects of endothelin-A receptor inhibition. Wolfárd, A., Szalay, L., Kaszaki, J., Sahin-Tóth, G., Vangel, R., Balogh, A., Boros, M. Transplantation (2002) [Pubmed]
  16. Haemodynamic and hormonal changes during haemorrhage in conscious dogs treated with an endothelin-A receptor antagonist. Höhne, C., Francis, R.C., Kaczmarczyk, G., Boemke, W. Clin. Sci. (2002) [Pubmed]
  17. Comparative effects of endothelin and neurotensin on intrinsic cardiac neurons in situ. Armour, J.A. Peptides (1996) [Pubmed]
  18. Endothelin- and sarafotoxin-induced phosphoinositide hydrolysis in cultured canine tracheal smooth muscle cells. Yang, C.M., Yo, Y.L., Ong, R., Hsieh, J.T. J. Neurochem. (1994) [Pubmed]
  19. Renal actions of endothelin-1 under endothelin receptor blockade by BE-18257B. Syed, N., Gulmi, F.A., Chou, S.Y., Mooppan, U.M., Kim, H. J. Urol. (1998) [Pubmed]
  20. Nitric oxide inhibition unmasks ischemic myocardium-derived vasoconstrictor signals activating endothelin type A receptor of coronary microvessels. Takahashi, K., Komaru, T., Takeda, S., Sato, K., Kanatsuka, H., Shirato, K. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  21. Endothelin-a receptor blockade does not debilitate the cardiovascular and hormonal adaptation to xenon or isoflurane anesthesia in dogs. Francis, R.C., Höhne, C., Klein, A., Donaubauer, B., Kaisers, U., Boemke, W. Exp. Biol. Med. (Maywood) (2006) [Pubmed]
  22. Hepatoprotective effect of the endothelin receptor antagonist TAK-044 against ischemia-reperfusion injury in the canine liver. Kitayama, Y., Yamanaka, N., Kawamura, E., Kuroda, N., Okamoto, E. Hepatology (1997) [Pubmed]
  23. Endothelin-dependent tone limits acetylcholine-induced dilation of resistance coronary vessels after blockade of NO formation in conscious dogs. Ming, Z., Parent, R., Thorin, E., Lavallée, M. Hypertension (1998) [Pubmed]
  24. Hemorrhage during isoflurane-nitrous oxide anesthesia: effects of endothelin-A or angiotensin II receptor blockade or both. Höhne, C., Vogler, P., Frerking, I., Francis, R.C., Swenson, E.R., Kaczmarczyk, G., Boemke, W. Anesthesiology (2004) [Pubmed]
  25. The selective endothelin-A-receptor antagonist LU 135.252 inhibits the direct arrhythmogenic action of endothelin-1. Merkely, B., Szabó, T., Gellér, L., Kiss, O., Horkay, F., Raschack, M., Juhász-Nagy, A. J. Cardiovasc. Pharmacol. (2000) [Pubmed]
  26. Endothelin-A receptor antagonism improves small bowel graft perfusion and structure after ischemia and reperfusion. Wolfárd, A., Vangel, R., Szalay, L., Kaszaki, J., Haulik, L., Balogh, A., Nagy, S., Boros, M. Transplantation (1999) [Pubmed]
  27. Early activation of cardiac and renal endothelin systems in experimental heart failure. Motte, S., van Beneden, R., Mottet, J., Rondelet, B., Mathieu, M., Havaux, X., Lause, P., Clercx, C., Ketelslegers, J.M., Naeije, R., McEntee, K. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
  28. Nonselective endothelin-receptor antagonism attenuates hemodynamic changes after massive pulmonary air embolism in dogs. Tanus-Santos, J.E., Gordo, W.M., Udelsmann, A., Cittadino, M.H., Moreno, H. Chest (2000) [Pubmed]
  29. Expression of endothelin-1 and effects of an endothelin receptor antagonist, TAK-044, at reperfusion after cold preservation in a canine lung transplantation model. Mizutani, H., Minamoto, K., Aoe, M., Yamashita, M., Date, H., Andou, A., Shimizu, N. J. Heart Lung Transplant. (1998) [Pubmed]
 
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