OBJECTIVES: The physiological effects of polymorphisms of the renin-angiotensin-aldosterone system (RAAS) are poorly understood. Long-term effects of genetic variants can be studied in cross-sectional linkage studies. In this study, we examined the short-term effects of genetic polymorphisms of the angiotensin II AT1 - and AT2-receptor subtypes in humans by means of angiotensin II infusion. METHODS: In 120 male, white, young (26 +/- 3 years) subjects with normal or mildly elevated blood pressure, changes in mean arterial blood pressure, aldosterone levels, glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured in response to angiotensin II infusion (0.5 ng/kg per min and 3.0 ng/kg per min, each over 30 min). The -2228 G/A polymorphism of the AT1-receptor gene, and the +1675 G/A polymorphism of the AT2-receptor gene were determined by restriction digestion and single strand conformation polymorphism analysis, respectively. RESULTS: Infusion of angiotensin II resulted in an increase in mean arterial pressure, serum aldosterone levels and GFR, and in a decrease in RPF (all P< 0.001). However, at similar baseline mean arterial pressure, aldosterone levels, and renal haemodynamics, the response to angiotensin II did not significantly differ across the AT1 - and AT2-receptor genotypes with the sample size of our study being adequate to detect relevant differences across the genotypes with a power of > 90% for all parameters. CONCLUSIONS: The response to angiotensin II infusion does not differ across the the AT1- and AT2-receptor genotypes examined in our study. However, long-term effects of variants of angiotensin II receptor genes cannot be ruled out with this approach.
OBJECTIVES: The physiological effects of polymorphisms of the renin-angiotensin-aldosterone system (RAAS) are poorly understood. Long-term effects of genetic variants can be studied in cross-sectional linkage studies. In this study, we examined the short-term effects of genetic polymorphisms of the angiotensin IIAT1 - and AT2-receptor subtypes in humans by means of angiotensin II infusion. METHODS: In 120 male, white, young (26 +/- 3 years) subjects with normal or mildly elevated blood pressure, changes in mean arterial blood pressure, aldosterone levels, glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured in response to angiotensin II infusion (0.5 ng/kg per min and 3.0 ng/kg per min, each over 30 min). The -2228 G/A polymorphism of the AT1-receptor gene, and the +1675 G/A polymorphism of the AT2-receptor gene were determined by restriction digestion and single strand conformation polymorphism analysis, respectively. RESULTS: Infusion of angiotensin II resulted in an increase in mean arterial pressure, serum aldosterone levels and GFR, and in a decrease in RPF (all P< 0.001). However, at similar baseline mean arterial pressure, aldosterone levels, and renal haemodynamics, the response to angiotensin II did not significantly differ across the AT1 - and AT2-receptor genotypes with the sample size of our study being adequate to detect relevant differences across the genotypes with a power of > 90% for all parameters. CONCLUSIONS: The response to angiotensin II infusion does not differ across the the AT1- and AT2-receptor genotypes examined in our study. However, long-term effects of variants of angiotensin II receptor genes cannot be ruled out with this approach.
Authors: U Muscha Steckelings; Robert E Widdop; Edward D Sturrock; Lizelle Lubbe; Tahir Hussain; Elena Kaschina; Thomas Unger; Anders Hallberg; Robert M Carey; Colin Sumners Journal: Pharmacol Rev Date: 2022-10 Impact factor: 18.923