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High human renin hypertension in transgenic rats
J Bohlender1, A Fukamizu, A Lippoldt
1Franz Volhard Clinic, Berlin, FRG.
Hypertension (Dallas, Tex. : 1979)
|January 1, 1997
Summary
Researchers created a new rat model for high renin hypertension by combining human angiotensinogen and renin genes. This double transgenic rat develops severe hypertension and cardiac hypertrophy, offering a unique tool for studying renin-induced diseases.
Area of Science:
- Cardiovascular Research
- Genetics and Genomics
- Translational Medicine
Background:
- Hypertension is a major global health concern with complex genetic and physiological underpinnings.
- The renin-angiotensin-aldosterone system (RAAS) plays a critical role in blood pressure regulation.
- Existing animal models do not fully recapitulate human renin-mediated hypertension.
Purpose of the Study:
- To develop a novel transgenic rat model that spontaneously exhibits high renin hypertension.
- To investigate the genetic and pathophysiological mechanisms of renin-induced hypertension.
- To provide a platform for testing therapeutic interventions targeting the RAAS.
Main Methods:
- Generation of two transgenic rat strains: one expressing human angiotensinogen and another expressing human renin.
- Crossing these strains to produce double transgenic rats harboring both human genes.
- Phenotypic characterization including blood pressure measurement, survival analysis, and histological examination of cardiac and renal tissues.
- Pharmacological intervention with an ACE inhibitor (lisinopril) and a human renin inhibitor (remikiren).
Main Results:
- Double transgenic rats developed severe hypertension (mean systolic pressure ~200 mm Hg) and reduced lifespan without treatment.
- Elevated human plasma renin and angiotensinogen concentrations were observed in transgenic rats compared to controls.
- Significant cardiac hypertrophy and distinct renal pathology were evident in the double transgenic rats.
- Both lisinopril and remikiren effectively normalized blood pressure in the model.
Conclusions:
- The developed double transgenic rat model accurately mimics spontaneously high human renin hypertension.
- This model facilitates the simultaneous investigation of genetic and pathophysiological aspects of renin-induced hypertension.
- The model offers a unique opportunity to study human renin in vivo within a rat system, aiding in the development of targeted therapies.