This Article Full Text Full Text (PDF) 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 Google Scholar Google Scholar Articles by Barton, M. Articles by Omata, M. Search for Related Content PubMed PubMed Citation Articles by Barton, M. Articles by Omata, M. Related Collections Animal models of human disease Pathophysiology Risk Factors Hypertension - basic studies Receptor pharmacology Endothelium/vascular type/nitric oxide Mechanism of atherosclerosis/growth factors Other Vascular biology

(Circulation. 2000;101:e228.)
© 2000 American Heart Association, Inc.

Circulation Electronic Pages

Hypertension, Diabetes Mellitus, Hypercholesterolemia, and Endothelin B Receptor-Mediated Renal Nitric Oxide Release

Matthias Barton, MD; Livius V. d’Uscio, PhD

Department of Cardiology, University Hospital Zürich, Cardiovascular Research Laboratory, Institute of Physiology, University of Zürich, CH-8091 Zürich, Switzerland., MatthiasBarton@compuserve.com

	Introduction

 
To the Editor:

Kakoki et al¹ recently reported a reduced endothelin (ET) B receptor–mediated release of nitric oxide (NO) in renal perfusates of experimental models of hypertension, diabetes mellitus, and hypercholesterolemia, as measured by H₂O₂-based chemiluminescence. Reduced immunostaining for endothelial ET_B receptors, as measured by semiquantitative immunohistochemistry, was observed in all experimental models, whereas staining for endothelial NO synthase (eNOS) was reduced in salt-sensitive Dahl rats but not spontaneously hypertensive (SHR) or hypercholesterolemic rats. Although interesting, these observations must be interpreted with caution.

In SHR, the release of NO was not impaired, which contrasts with previously published data. eNOS activity is increased in SHR, but endothelial NO levels are reduced due to inactivation by the superoxide anion.² This discrepancy is not commented on by the authors, and the previously published work was not cited.

In experimental diabetes and hypercholesterolemia, renal eNOS expression was unchanged, while ET_B-mediated renal NO release was markedly reduced. The authors propose that the reduced expression of the ET_B receptor accounts for the reduction in NO release without having investigated the effect of antioxidants such as superoxide dismutase, vitamin C, or N-acetylcysteine. Finally, the authors used whole, perfused kidneys to measure NO release in the renal vein, without assessing ET_B receptor and NO synthase expression in nonvascular renal tissue, which also affects NO levels in the perfusate.

Interestingly, an infusion of the ET_B agonist BQ-3020 of <10^-10 mol/L reduced renal perfusion in salt-resistant Dahl rats, whereas renal perfusion in salt-sensitive animals was increased. The . . . [Full Text of this Article]

Yasunobu Hirata, MD; Masao Kakoki, MD; Hiroshi Hayakawa, MD; Akihiro Tojo, MD; Daisuke Nagata, MD; Etsu Suzuki, MD; Kenjiro Kimura, MD; Atsuo Goto, MD; Kazuya Kikuchi, PhD; Tetsuo Nagano, PhD; Masao Omata, MD

The Second Department of Internal Medicine, Faculties of Medicine and Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan, hirata-2im@h.u-tokyo.ac.jp