John P Collister1, Michael D Hendel. 1. University of Minnesota, Department of Veterinary PathoBiology, St. Paul 55108, USA. colli066@tc.umn.edu
Abstract
HYPOTHESIS: The following studies were designed to test the hypothesis that Ang (1-7) contributes to the chronic hypotensive effects of the angiotensin II AT(1)-receptor antagonist, losartan, in normal rats. INTRODUCTION: We have previously shown a chronic, hypotensive response to the AT(1)-receptor antagonist, losartan, in normotensive rats. The mechanism of this response is not completely understood. Previous studies by others have demonstrated a role for Ang (1-7) in the beneficial antihypertensive effects of angiotensin-converting enzyme (ACE) inhibition. This is thought to be due to vasodilatory effects of increased levels of Ang (1-7) during ACE inhibition. Since it has now been shown that Ang (1-7) levels are also increased during AT(1) antagonism, we designed experiments to test the hypothesis above. MATERIALS AND METHODS: Sprague-Dawley rats were instrumented with venous catheters and radiotelemetric pressure transducers and commenced on a normal (0.4%) NaCl diet. Arterial pressure responses were measured in rats treated with losartan (10 mg/kg/day) (LOS rats, n=8) and compared with those treated with losartan and the Ang (1-7) antagonist, A779 (24 g/kg/hour) (A779/LOS rats, n=11) for 10 days. RESULTS: By day 7 of treatment, mean arterial pressure had dropped by 27+1 mmHg in LOS rats, in contrast with a decrease of only 21+2 mmHg in A779/LOS rats. This attenuated response in rats treated with A779 became more prominent and continued through day 10 of losartan treatment. CONCLUSION: These results support the hypothesis that the chronic hypotensive effects of losartan in normal rats are mediated in part through the actions of Ang (1-7).
HYPOTHESIS: The following studies were designed to test the hypothesis that Ang (1-7) contributes to the chronic hypotensive effects of the angiotensin II AT(1)-receptor antagonist, losartan, in normal rats. INTRODUCTION: We have previously shown a chronic, hypotensive response to the AT(1)-receptor antagonist, losartan, in normotensive rats. The mechanism of this response is not completely understood. Previous studies by others have demonstrated a role for Ang (1-7) in the beneficial antihypertensive effects of angiotensin-converting enzyme (ACE) inhibition. This is thought to be due to vasodilatory effects of increased levels of Ang (1-7) during ACE inhibition. Since it has now been shown that Ang (1-7) levels are also increased during AT(1) antagonism, we designed experiments to test the hypothesis above. MATERIALS AND METHODS:Sprague-Dawley rats were instrumented with venous catheters and radiotelemetric pressure transducers and commenced on a normal (0.4%) NaCl diet. Arterial pressure responses were measured in rats treated with losartan (10 mg/kg/day) (LOS rats, n=8) and compared with those treated with losartan and the Ang (1-7) antagonist, A779 (24 g/kg/hour) (A779/LOS rats, n=11) for 10 days. RESULTS: By day 7 of treatment, mean arterial pressure had dropped by 27+1 mmHg in LOS rats, in contrast with a decrease of only 21+2 mmHg in A779/LOS rats. This attenuated response in rats treated with A779 became more prominent and continued through day 10 of losartan treatment. CONCLUSION: These results support the hypothesis that the chronic hypotensive effects of losartan in normal rats are mediated in part through the actions of Ang (1-7).
Authors: Anderson J Ferreira; Tatiane M Murça; Rodrigo A Fraga-Silva; Carlos Henrique Castro; Mohan K Raizada; Robson A S Santos Journal: Int J Hypertens Date: 2012-01-26 Impact factor: 2.420
Authors: Christoph Schindler; Kristina Guenther; Cosima Hermann; Carlos M Ferrario; Christoph Schroeder; Sven Haufe; Jens Jordan; Wilhelm Kirch Journal: PLoS One Date: 2014-09-29 Impact factor: 3.240
Authors: John P Collister; Heather Taylor-Smith; Donna Drebes; David Nahey; Jun Tian; Matthew C Zimmerman Journal: Oxid Med Cell Longev Date: 2016-01-06 Impact factor: 6.543