Genetic loci contribute to the progression of vascular and cardiac hypertrophy in salt-sensitive spontaneous hypertension

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 F-2 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 F-2-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.