This Article Full Text Full Text (PDF) All Versions of this Article: 23/7/1211    most recent 01.ATV.0000079509.20542.C9v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted 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 Siegel, A.-K. Articles by Kreutz, R. Search for Related Content PubMed PubMed Citation Articles by Siegel, A.-K. Articles by Kreutz, R. Related Collections Other Ethics and Policy Cardiovascular imaging agents/Techniques Glucose intolerance Embolic stroke

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1211.)
© 2003 American Heart Association, Inc.

Vascular Biology

Genetic Loci Contribute to the Progression of Vascular and Cardiac Hypertrophy in Salt-Sensitive Spontaneous Hypertension

Anja-Kristin Siegel; Michael Planert; Sibylle Rademacher; Ali Poyan Mehr; Peter Kossmehl; Markus Wehland; Monika Stoll; Reinhold Kreutz

From the Institut für Klinische Pharmakologie and Toxikologie (P.K.), Benjamin Franklin Hospital, Freie Universität Berlin and Medizinische Klinik I, Universität Kiel (M.S.), Germany.

Correspondence to Reinhold Kreutz, MD, FAHA, Benjamin Franklin Klinikum, Freie Universität Berlin, Hindenburgdamm 30, 12203 Berlin, Germany. E-mail Kreutz{at}medizin.fu-berlin.de

Objective— The salt-sensitive Dahl rat and the spontaneously hypertensive rat develop comparable spontaneous hypertension on a low-salt diet, whereas only the salt-sensitive Dahl rat strain develops a striking increase in blood pressure and cardiovascular hypertrophy on a high-salt diet. We set out to identify quantitative trait loci (QTLs) contributing to the progression of salt-induced organ damage in hypertension by studying an F₂ population derived from both strains.

Methods and Results— We determined systolic blood pressure (SBP), vascular aortic hypertrophy (AH), cardiac left ventricular (LV) hypertrophy (LVH), and LV fibrosis in 230 male F₂-animals on a high-salt diet. A strong correlation between AH and LVH was found (r=0.58, P<0.0001), and genome-wide QTL mapping detected suggestive or significant QTLs in overlapping chromosomal fragments for AH and LVH on chromosomes 1, 3, and 19, respectively. A significant influence of SBP on the extent of LVH and AH was evident at all QTLs, although significant linkage to SBP (together with LVH) was only found on chromosome 9. No QTLs for LV fibrosis were detected.

Conclusions— This study demonstrates a strong correlation between AH and LVH in salt-sensitive hypertension and identifies QTLs contributing to the progression of cardiovascular hypertrophy in this condition.

Key Words: hypertension • hypertrophy • heart • aorta • genetics

This article has been cited by other articles:

				J. H. Wiessner, M. R. Garrett, R. J. Roman, and N. S. Mandel Dissecting the genetic basis of kidney tubule response to hyperoxaluria using chromosome substitution strains Am J Physiol Renal Physiol, August 1, 2009; 297(2): F301 - F306. [Abstract] [Full Text] [PDF]

				D. L. Mattson, M. R. Dwinell, A. S. Greene, A. E. Kwitek, R. J. Roman, H. J. Jacob, and A. W. Cowley Jr. Chromosome substitution reveals the genetic basis of Dahl salt-sensitive hypertension and renal disease Am J Physiol Renal Physiol, September 1, 2008; 295(3): F837 - F842. [Abstract] [Full Text] [PDF]

				D. Graham, M. W. McBride, M. Gaasenbeek, K. Gilday, E. Beattie, W. H. Miller, J. D. McClure, J. M. Polke, A. Montezano, R. M. Touyz, et al. Candidate Genes That Determine Response to Salt in the Stroke-Prone Spontaneously Hypertensive Rat: Congenic Analysis Hypertension, December 1, 2007; 50(6): 1134 - 1141. [Abstract] [Full Text] [PDF]

				M. Pravenec and T. W. Kurtz Molecular Genetics of Experimental Hypertension and the Metabolic Syndrome: From Gene Pathways to New Therapies Hypertension, May 1, 2007; 49(5): 941 - 952. [Abstract] [Full Text] [PDF]

				S. J. Lee, J. Liu, A. M. Westcott, J. A. Vieth, S. J. DeRaedt, S. Yang, B. Joe, and G. T. Cicila Substitution Mapping in Dahl Rats Identifies Two Distinct Blood Pressure Quantitative Trait Loci Within 1.12- and 1.25-Mb Intervals on Chromosome 3 Genetics, December 1, 2006; 174(4): 2203 - 2213. [Abstract] [Full Text] [PDF]

				S. Rubattu, G. Bigatti, A. Evangelista, C. Lanzani, R. Stanzione, L. Zagato, P. Manunta, S. Marchitti, V. Venturelli, G. Bianchi, et al. Association of Atrial Natriuretic Peptide and Type A Natriuretic Peptide Receptor Gene Polymorphisms With Left Ventricular Mass in Human Essential Hypertension J. Am. Coll. Cardiol., August 1, 2006; 48(3): 499 - 505. [Abstract] [Full Text] [PDF]

				D. Gauguier, J. Behmoaras, K. Argoud, S. P. Wilder, C. Pradines, M. T. Bihoreau, M. Osborne-Pellegrin, and M. P. Jacob Chromosomal Mapping of Quantitative Trait Loci Controlling Elastin Content in Rat Aorta Hypertension, March 1, 2005; 45(3): 460 - 466. [Abstract] [Full Text] [PDF]

				A.-K. Siegel, P. Kossmehl, M. Planert, A. Schulz, M. Wehland, M. Stoll, J. A. Bruijn, E. de Heer, and R. Kreutz Genetic linkage of albuminuria and renal injury in Dahl salt-sensitive rats on a high-salt diet: comparison with spontaneously hypertensive rats Physiol Genomics, July 8, 2004; 18(2): 218 - 225. [Abstract] [Full Text] [PDF]