This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 42/4/562    most recent 01.HYP.0000088852.28814.E2v1 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 Büssemaker, E. Articles by Brandes, R. P. Search for Related Content PubMed PubMed Citation Articles by Büssemaker, E. Articles by Brandes, R. P. Related Collections Cardiovascular Pharmacology Endothelium/vascular type/nitric oxide

(Hypertension. 2003;42:562.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Aged Spontaneously Hypertensive Rats Exhibit a Selective Loss of EDHF-Mediated Relaxation in the Renal Artery

Eckhart Büssemaker; Rüdiger Popp; Beate Fisslthaler; Christiana M. Larson; Ingrid Fleming; Rudi Busse; Ralf P. Brandes

From the Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Frankfurt am Main, Germany.

Correspondence to Ralf P. Brandes, MD, Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Theodor-Stern-Kai 7, D-60596 Frankfurt am Main, Germany. E-mail r.brandes{at}em.uni-frankfurt.de

Endothelium-dependent relaxation is frequently attenuated in hypertension. We hypothesized that the contribution of the endothelium-derived hyperpolarizing factor (EDHF) to the acetylcholine (ACh)-induced, endothelium-dependent relaxation is attenuated with aging in the renal artery of spontaneously hypertensive rats (SHR) compared with age-matched Wistar-Kyoto (WKY) rats. ACh-induced, NO-mediated relaxation was identical in young (8-week-old) WKY and SHR, whereas EDHF-mediated relaxations (assessed in the presence of N-nitro-L-arginine and diclofenac) were much more pronounced in SHR than WKY. KCl-induced relaxations were more pronounced in vessels from young WKY rats than from young SHR. The cytochrome P450 inhibitor sulfaphenazole significantly inhibited EDHF-mediated relaxation in vessels from young SHR but not WKY. Vessels from old (22 months) SHR exhibited a slightly reduced NO-mediated relaxation but a complete loss of EDHF-mediated responses. In contrast, aging did not affect EDHF-mediated responses in WKY. Moreover, ACh-induced hyperpolarization and resting membrane potential were decreased in old SHR but not in WKY. KCl-induced relaxation increased with age in WKY, whereas no response to KCl was recorded in arteries from aged SHR. In vessels from old WKY but not old SHR, mRNA expression of the Na-K-ATPase subunit ₂ was increased by 2-fold compared with young animals. These data indicate that the increase in EDHF responses in renal arteries from aged WKY can be attributed to the release of K⁺ ions from the endothelium, whereas increased EDHF responses in renal arteries from young SHR can be attributed to a sulfaphenazole-sensitive cytochrome P450-dependent EDHF.

Key Words: endothelium • nitric oxide • acetylcholine • endothelium-derived factors • animal models of hypertension • renal artery

This article has been cited by other articles:

				B. Ponnuchamy and R. A. Khalil Cellular mediators of renal vascular dysfunction in hypertension Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2009; 296(4): R1001 - R1018. [Abstract] [Full Text] [PDF]

				S. G. Denniss and J. W. E. Rush Impaired hemodynamics and endothelial vasomotor function via endoperoxide-mediated vasoconstriction in the carotid artery of spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H1038 - H1047. [Abstract] [Full Text] [PDF]

				P. M. Vanhoutte and E. H. C. Tang Endothelium-dependent contractions: when a good guy turns bad! J. Physiol., November 15, 2008; 586(22): 5295 - 5304. [Abstract] [Full Text] [PDF]

				X. Tang, N. Aggarwal, B. B. Holmes, H. Kuhn, and W. B. Campbell Age-related decrease in 15-lipoxygenase contributes to reduced vasorelaxation in rabbit aorta Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H679 - H687. [Abstract] [Full Text] [PDF]

				M. L. Gaubert, D. Sigaudo-Roussel, M. Tartas, G. Berrut, J. L. Saumet, and B. Fromy Endothelium-derived hyperpolarizing factor as an in vivo back-up mechanism in the cutaneous microcirculation in old mice J. Physiol., December 1, 2007; 585(2): 617 - 626. [Abstract] [Full Text] [PDF]

				X. Zhao, J. E. Quigley, J. Yuan, M.-H. Wang, Y. Zhou, and J. D. Imig PPAR-{alpha} activator fenofibrate increases renal CYP-derived eicosanoid synthesis and improves endothelial dilator function in obese Zucker rats Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2187 - H2195. [Abstract] [Full Text] [PDF]

				J. Bellien, R. Joannides, M. Iacob, P. Arnaud, and C. Thuillez Evidence for a basal release of a cytochrome-related endothelium-derived hyperpolarizing factor in the radial artery in humans Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1347 - H1352. [Abstract] [Full Text] [PDF]

				R. P. Brandes, I. Fleming, and R. Busse Endothelial aging Cardiovasc Res, May 1, 2005; 66(2): 286 - 294. [Abstract] [Full Text] [PDF]

				P. D. Taylor, I. Y. Khan, M. A. Hanson, and L. Poston Impaired EDHF-mediated vasodilatation in adult offspring of rats exposed to a fat-rich diet in pregnancy J. Physiol., August 1, 2004; 558(3): 943 - 951. [Abstract] [Full Text] [PDF]