RGD Reference Report - A pharmacogenetic approach to blood pressure in Lyon hypertensive rats. A chromosome 2 locus influences the response to a calcium antagonist. - Rat Genome Database

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A pharmacogenetic approach to blood pressure in Lyon hypertensive rats. A chromosome 2 locus influences the response to a calcium antagonist.

Authors: Vincent, M  Samani, NJ  Gauguier, D  Thompson, JR  Lathrop, GM  Sassard, J 
Citation: Vincent M, etal., J Clin Invest 1997 Oct 15;100(8):2000-6
RGD ID: 61058
Pubmed: PMID:9329963   (View Abstract at PubMed)
PMCID: PMC508389   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI119731   (Journal Full-text)

In a backcross population (n = 281) derived from a cross of the Lyon hypertensive rat with Lyon normotensive rat, we investigated whether genetic factors influence the acute cardiovascular responses to pharmacological modulation of the renin-angiotensin system, the sympathetic nervous system, and the voltage-sensitive L-type calcium channels. Using microsatellite markers, a quantitative trait locus was identified and mapped on rat chromosome 2 that specifically influences the systolic (peak LOD score 4.4) and diastolic (peak LOD score 4.1) blood pressure responses to administration of a dihydropyridine calcium antagonist, PY108-068. The locus accounted for 10.3 and 10.4% of the total variances in the systolic and diastolic responses to PY108-068, respectively. In marked contrast, the locus had no effect on either basal blood pressure or on the responses to acute administration of a ganglionic blocking agent, trimetaphan, or of an angiotensin II subtype 1 receptor antagonist, losartan. These findings provide strong direct support for the paradigm that genetic factors may influence the response to antihypertensive drugs and suggest that the heterogeneity seen in the responses to different antihypertensive agents in human essential hypertension may have a significant genetic determination.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension  IDA 61058 RGD 
hypertension  IAGP 61058 RGD 
hypertension MODEL: spontaneousIAGP 61058compared to LN/MavRGD 
hypertension MODEL: controlIAGP 61058compared with LH/MavRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype


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Objects Annotated

QTLs
Bp357  (Blood pressure QTL 357)
Bp50  (Blood pressure QTL 50)

Strains
LH/Mav  (NA)
LH/MavRrrc  (Lyon Hypertensive)
LN/Mav  (NA)
LN/MavRrrc  (lyon normotensive)

Objects referenced in this article
Marker D2Mit14 D2Mit14 Rattus norvegicus
Marker D2Mit15 D2Mit15 Rattus norvegicus
QTL Bw50 Body weight QTL 50 Rattus norvegicus

Additional Information