Exploiting Rat Genetics to Investigate Hypertensive End-Organ Damage
Transgenic animal models are important tools, which have been extensively used to gain insight into the molecular mechanisms of human diseases. We have created two transgenic consomic rat strains, in which malignant hypertension can be induced by administration of a nontoxic xenobiotic. Studies combining quantitative trait locus (QTL) analysis, pathological examination and molecular biological investigation have demonstrated that the renal renin–angiotensin system (RAS), especially angiotensin converting enzyme (Ace), is a key factor affecting the degree of hypertensive kidney damage in these strains.
KeywordsQuantitative Trait Locus Malignant Hypertension Gastric Gavage Consomic Strain Kim1 Expression
This work was supported by the Wellcome Trust CVRI and Functional Genomics initiatives. JM is a recipient of the Wellcome Trust Principle Fellowship.
- 9.Santos RA, Krieger EM, Greene LJ. An improved fluorometric assay of rat serum and plasma converting enzyme. Hypertension. 1985;7(2):244–252.Google Scholar
- 30.Unger T, Ganten D, Lang RE, Schölkens BA. Is tissue converting enzyme inhibition a determinant of the antihypertensive efficacy of converting enzyme inhibitors? Studies with the two different compounds, Hoe498 and MK421, in spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1984;6:5872–5880.CrossRefGoogle Scholar
- 35.Jafarian-Tehrani M, Listwak S, Barrientos RM, Michaud A, Corvol P, Sternberg EM. Exclusion of angiotensin I-converting enzyme as a candidate gene involved in exudative inflammatory resistance in F344/N rats. Mol Med. 2000;6:4319–331.Google Scholar