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(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

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