This Article Full Text Full Text (PDF) All Versions of this Article: 41/6/1364    most recent 01.HYP.0000073782.30879.16v1 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 Kööbi, P. Articles by Pörsti, I. Search for Related Content PubMed PubMed Citation Articles by Kööbi, P. Articles by Pörsti, I. Related Collections Remodeling Cardiovascular Pharmacology ACE/Angiotension receptors Animal models of human disease Other hypertension Endothelium/vascular type/nitric oxide

(Hypertension. 2003;41:1364.)
© 2003 American Heart Association, Inc.

Scientific Contributions

AT₁ Receptor Blockade Improves Vasorelaxation in Experimental Renal Failure

Peeter Kööbi; Jarkko Kalliovalkama; Pasi Jolma; Jaana Rysä; Heikki Ruskoaho; Olli Vuolteenaho; Mika Kähönen; Ilkka Tikkanen; Meng Fan; Pauli Ylitalo; Ilkka Pörsti

From the Departments of Pharmacological Sciences (P.K., P.J., M.K., M.F., P.Y., I.P.) and Internal Medicine (I.P.), University of Tampere; Departments of Anesthesia and Intensive Care (J.K.), Clinical Physiology (M.K.), and Clinical Chemistry (P.Y.), Tampere University Hospital, Tampere; Departments of Pharmacology and Toxicology (J.R., H.R.) and Physiology (O.V.), Biocenter Oulu, University of Oulu, Oulu; Department of Medicine (I.T., I.P.), Helsinki University Central Hospital, Helsinki; and Minerva Institute for Medical Research (I.T.), Biomedicum Helsinki, Helsinki, Finland.

Correspondence to Ilkka Pörsti, MD, Medical School, Department of Internal Medicine, FIN-33014 University of Tampere, Finland. E-mail ilkka.porsti{at}uta.fi

It is not known whether angiotensin II type 1 receptor antagonists can influence the function and morphology of small arteries in renal failure. We investigated the effect of 8-week losartan therapy (20 mg/kg per day) on isolated mesenteric resistance arteries by wire and pressure myographs in 5/6 nephrectomized rats. Plasma urea nitrogen was elevated 1.6-fold after nephrectomy, and ventricular synthesis of atrial and B-type natriuretic peptides was increased 2.2-fold and 1.7-fold, respectively, whereas blood pressure was not affected. Losartan did not influence these variables. The endothelium-mediated relaxation to acetylcholine was impaired in nephrectomized rats in the absence and presence of nitric oxide synthase and cyclooxygenase inhibition. Blockade of calcium-activated potassium channels by charybdotoxin and apamin reduced the remaining acetylcholine response, and this effect was less marked in nephrectomized than in sham-operated rats. Relaxation to levcromakalim, a vasodilator acting through adenosine triphosphate-sensitive potassium channels, was also impaired after nephrectomy. The arteries of nephrectomized rats showed eutrophic inward remodeling: Wall-to-lumen ratio was increased without change in wall cross-sectional area. All changes in arterial relaxation and morphology were normalized by losartan therapy. Aortic ACE content, measured by autoradiography, directly correlated to the plasma level of urea nitrogen, suggesting that renal failure has an enhancing influence on the vascular renin-angiotensin system. Losartan normalized relaxation and morphology of resistance arteries in experimental renal failure, independent of its influence on blood pressure, impaired kidney function, or volume overload. The mechanism of improved vasodilation by losartan may include enhanced relaxation through potassium channels.

Key Words: arteries • receptors, angiotensin II • endothelium-derived factors • angiotensin II • potassium channels • kidney failure

This article has been cited by other articles:

				P. Koobi, T. I. Vehmas, P. Jolma, J. Kalliovalkama, M. Fan, O. Niemela, H. Saha, M. Kahonen, P. Ylitalo, J. Rysa, et al. High-calcium vs high-phosphate intake and small artery tone in advanced experimental renal insufficiency Nephrol. Dial. Transplant., October 1, 2006; 21(10): 2754 - 2761. [Abstract] [Full Text] [PDF]

				S. Bro, F. Moeller, C. B. Andersen, K. Olgaard, and L. B. Nielsen Increased Expression of Adhesion Molecules in Uremic Atherosclerosis in Apolipoprotein-E-Deficient Mice J. Am. Soc. Nephrol., June 1, 2004; 15(6): 1495 - 1503. [Abstract] [Full Text] [PDF]