Mapping of genetic determinants of the sympathoneural response to stress.
Activation of the sympathoadrenal system (SAS, comprising the sympathetic nervous system and the adrenal medulla) in response to stressful stimuli is an important defense mechanism as well as a contributor to several cardiovascular diseases. There is variability in the SAS response to stress, although the extent to which this is genetically regulated is unclear. Some rodent models, including the hereditary hypertriglyceridemic (hHTg) rat, are hyperresponsive to stress. We investigated whether quantitative trait loci (QTLs) that affect sympathoadrenal response to stress could be identified. Second filial generation rats (n = 189) derived from a cross of the hHTg rat and the Brown Norway rat had plasma norepinephrine (NE) and epinephrine (Epi) levels, indices of activation of the sympathoneural and adrenal medulla components, respectively, measured in the resting state and in response to an immobilization stress. Responses were assessed early (20 min) and late (120 min) after the application of the stress. A genome scan was conducted using 153 microsatellite markers. Two QTLs (maximum peak LOD scores of 4.17 and 3.52, respectively) influencing both the early and late plasma NE response to stress were found on chromosome 10. Together, the QTLs accounted for approximately 20% of the total variation in both the early and late NE responses in the F(2) rats. Interestingly, the QTLs had no effect on plasma Epi response to stress. These findings provide evidence for a genetic determination of the response of a specific component of the SAS response to stress. Genetically determined variation in sympathetic nervous system response to stress may contribute to cardiovascular diseases.
Klimes
I
I
Diabetes and Nutrition Research Laboratory, Slovak Academy of Sciences, Bratislava, Slovakia.
Weston
K
K
Gasperíková
D
D
Kovács
P
P
Kvetnanský
R
R
Jezová
D
D
Dixon
R
R
Thompson
J R
JR
Seböková
E
E
Samani
N J
NJ
D000818:Animals; D001794:Blood Pressure; D002395:Catecholamines / Q000378:metabolism; D002874:Chromosome Mapping; D019295:Computational Biology; D003433:Crosses, Genetic; D004837:Epinephrine / Q000097:blood; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009638:Norepinephrine / Q000097:blood; D010641:Phenotype; D040641:Quantitative Trait Loci; D051381:Rats; D011914:Rats, Inbred BN; D013045:Species Specificity; D013312:Stress, Physiological; D013564:Sympathetic Nervous System / Q000473:pathology*; D013997:Time Factors
D002395:Catecholamines; D005819:Genetic Markers; D009638:Norepinephrine; D004837:Epinephrine