This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Seo, B. Articles by Lüscher, T. F. Search for Related Content PubMed PubMed Citation Articles by Seo, B. Articles by Lüscher, T. F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Seniors' Health

(Hypertension. 1995;25:501-506.)
© 1995 American Heart Association, Inc.

Articles

ET_A and ET_B Receptors Mediate Contraction to Endothelin-1 in Renal Artery of Aging SHR

Effects of FR139317 and Bosentan

Presented at the 48th Annual Fall Conference and Scientific Sessions of the Council for High Blood Pressure Research of the American Heart Association, Chicago, Ill, September 27-30, 1994.

Bonggwan Seo; Thomas F. Lüscher

From the Department of Research, University Hospital, Basel (B.S., T.F.L.); Cardiology, Cardiovascular Research, University Hospital, Bern (T.F.L.), Switzerland; and the Department of Medicine, Gyeongsang National University Hospital, Chinju, Korea (B.S.).

Correspondence to Thomas F. Lüscher, MD, Division of Cardiology, University Hospital/Inselspital, CH-3010 Bern, Switzerland.

Abstract We characterized vascular endothelin receptors of the renal artery from adult (12 to 16 weeks of age) and old (72 to 76 weeks) spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). Vessels were suspended in organ chambers (37°C, aerated with 95% O₂/5% CO₂), and isometric tension was recorded. The endothelin-A (ET_A) receptor antagonist FR139317, the combined ET_A/ET_B receptor antagonist bosentan, and the ET_B-selective agonist sarafotoxin S6c were used. In old (and less so in adult) SHR, cumulative concentration-contraction curves to endothelin-1 showed a small contraction resistant to FR139317 (10^-5 mol/L) at 3x10^-9 to 10^-8 mol/L endothelin-1, which was completely inhibited by bosentan (10^-5 mol/L). This FR139317-resistant contraction to endothelin-1 was not present in WKY. Furthermore, in the presence of FR139317 (10^-5 mol/L), sarafotoxin S6c induced a stronger contraction in old SHR than in WKY (P<.05). In rings contracted with norepinephrine, sarafotoxin S6c caused endothelium-dependent relaxations in both strains; these relaxations were blocked by N-nitro-L-arginine methyl ester, indicating that nitric oxide is the mediator. In WKY but not SHR, release of nitric oxide by sarafotoxin S6c increased with age (P<.05). Thus, both ET_A and ET_B receptors mediate contraction to endothelin-1 in the renal artery from SHR but not WKY. ET_B receptors on vascular smooth muscle seem to be unmasked with age in SHR, whereas those on endothelium (mediating nitric oxide release) exhibit more efficient responses with age in WKY.

Key Words: renal artery • receptors, endothelin • endothelins • aging

This article has been cited by other articles:

				A. J. Donato, L. A. Lesniewski, and M. D. Delp The effects of aging and exercise training on endothelin-1 vasoconstrictor responses in rat skeletal muscle arterioles Cardiovasc Res, May 1, 2005; 66(2): 393 - 401. [Abstract] [Full Text] [PDF]

				S. K. Fellner and L. A. Parker Endothelin B receptor Ca2+ signaling in shark vascular smooth muscle: participation of inositol trisphosphate and ryanodine receptors J. Exp. Biol., September 1, 2004; 207(19): 3411 - 3417. [Abstract] [Full Text] [PDF]

				J. F. Reckelhoff and L. A. Fortepiani Novel Mechanisms Responsible for Postmenopausal Hypertension Hypertension, May 1, 2004; 43(5): 918 - 923. [Abstract] [Full Text] [PDF]

				P.M. Vanhoutte Ageing and endothelial dysfunction Eur. Heart J. Suppl., February 1, 2002; 4(suppl_A): A8 - A17. [Abstract] [PDF]

				K. Asai, R. K. Kudej, G. Takagi, A. B. Kudej, F. Natividad, Y.-T. Shen, D. E. Vatner, and S. F. Vatner Paradoxically Enhanced Endothelin-B Receptor-Mediated Vasoconstriction in Conscious Old Monkeys Circulation, May 15, 2001; 103(19): 2382 - 2386. [Abstract] [Full Text] [PDF]

				L. E. Spieker, V. Mitrovic, G. Noll, R. Pacher, M. R. Schulze, J.o. Muntwyler, C. Schalcher, W. Kiowski, T. F. Luscher, and on behalf of the ET 003 Investigators Acute hemodynamic and neurohumoral effects of selective ETA receptor blockade in patients with congestive heart failure J. Am. Coll. Cardiol., June 1, 2000; 35(7): 1745 - 1752. [Abstract] [Full Text] [PDF]

				M. Clozel, H. Ramuz, J.-P. Clozel, V. Breu, P. Hess, B.-M. Löffler, P. Coassolo, and S. Roux Pharmacology of Tezosentan, New Endothelin Receptor Antagonist Designed for Parenteral Use J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 840 - 846. [Abstract] [Full Text]

				P. Moreau Endothelin in hypertension: A role for receptor antagonists? Cardiovasc Res, September 1, 1998; 39(3): 534 - 542. [Abstract] [Full Text] [PDF]

				M. Gondré and G. J. Christ Endothelin-1-Induced Alterations in Phenylephrine-Induced Contractile Responses Are Largely Additive in Physiologically Diverse Rabbit Vasculature J. Pharmacol. Exp. Ther., August 1, 1998; 286(2): 635 - 642. [Abstract] [Full Text]

				L. V. d'Uscio, P. Moreau, S. Shaw, H. Takase, M. Barton, and T. F. Luscher Effects of Chronic ETA-Receptor Blockade in Angiotensin II-Induced Hypertension Hypertension, January 1, 1997; 29(1): 435 - 441. [Abstract] [Full Text] [PDF]

				C. F. Kung, P. Moreau, H. Takase, and T. F. Luscher L-NAME Hypertension Alters Endothelial and Smooth Muscle Function in Rat Aorta : Prevention by Trandolapril and Verapamil Hypertension, November 1, 1995; 26(5): 744 - 751. [Abstract] [Full Text]