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Research Article Free access | 10.1172/JCI119731

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

M Vincent, N J Samani, D Gauguier, J R Thompson, G M Lathrop, and J Sassard

ESA Centre National de la Recherche Scientifique 5014, Département de Physiologie et de Pharmacologie Clinique, Faculté de Pharmacie, Lyon 69373, France. vincent@rockefeller1.univ-lyon1.fr

Find articles by Vincent, M. in: JCI | PubMed | Google Scholar

ESA Centre National de la Recherche Scientifique 5014, Département de Physiologie et de Pharmacologie Clinique, Faculté de Pharmacie, Lyon 69373, France. vincent@rockefeller1.univ-lyon1.fr

Find articles by Samani, N. in: JCI | PubMed | Google Scholar

ESA Centre National de la Recherche Scientifique 5014, Département de Physiologie et de Pharmacologie Clinique, Faculté de Pharmacie, Lyon 69373, France. vincent@rockefeller1.univ-lyon1.fr

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ESA Centre National de la Recherche Scientifique 5014, Département de Physiologie et de Pharmacologie Clinique, Faculté de Pharmacie, Lyon 69373, France. vincent@rockefeller1.univ-lyon1.fr

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ESA Centre National de la Recherche Scientifique 5014, Département de Physiologie et de Pharmacologie Clinique, Faculté de Pharmacie, Lyon 69373, France. vincent@rockefeller1.univ-lyon1.fr

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ESA Centre National de la Recherche Scientifique 5014, Département de Physiologie et de Pharmacologie Clinique, Faculté de Pharmacie, Lyon 69373, France. vincent@rockefeller1.univ-lyon1.fr

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Published October 15, 1997 - More info

Published in Volume 100, Issue 8 on October 15, 1997
J Clin Invest. 1997;100(8):2000–2006. https://doi.org/10.1172/JCI119731.
© 1997 The American Society for Clinical Investigation
Published October 15, 1997 - Version history
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Abstract

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.

Version history
  • Version 1 (October 15, 1997): No description
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