Chromosome 1 QTL influences renal sympathetic nervous activity and its regulatory role in vascular and tubular functions in rat models of hypertension.
Hypothesis-generating for QTL-modulated renal sympathetic responses in hypertension models; leaves open translation to human renal denervation.
Two reciprocal congenic strains, WKYpch1.0 and SHRSPwch1.0, were constructed, respectively, by introgressing the stroke-prone spontaneously hypertensive rat (SHRSP)-derived fragment for the chromosome 1 blood pressure (BP) quantitative trait locus (QTL) into Wistar-Kyoto (WKY) rats and vice versa. 2. Under basal conditions with intact renal sympathetic nerves, the renal noradrenaline content and renal vascular resistance (RVR) were decreased in the order of SHRSP, SHRSPwch1.0, WKYpch1.0 and WKY, exhibiting reciprocal changes in the congenic strains according to the genotype of the chromosome 1 QTL. 3. Renal denervation resulted in significant effects on RVR and the fractional excretion of sodium only in SHRSP and WKYpch1.0, both of which harboured the SHRSP-derived fragment of chromosome 1 QTL. 4. Thus, chromosome 1 QTL may influence both renal sympathetic nervous activity and the regulatory role of the sympathetic nervous system in vascular and tubular functions. The reciprocal congenic strains are thereby unique models that may help in the search for intermediate phenotypes and empower functional deduction of candidate genes.
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Wang et al. (2008) studied this question.
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