TY - JOUR
T1 - Enalapril attenuates endothelin-1-induced hypertension via increased kinin survival
AU - Elmarakby, Ahmed A.
AU - Morsing, Peter
AU - Pollock, David M.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2003/6/1
Y1 - 2003/6/1
N2 - Recent studies have shown that angiotensin-converting enzyme (ACE) inhibitors attenuate endothelin-1 (ET-1)-induced hypertension, but the mechanisms for this effect have not been clarified. Initial experiments were conducted to contrast the effect of the ACE inhibitor enalapril, the combined ACE-neutral endopeptidase inhibitor omapatrilat, and the angiotensin II receptor antagonist candesartan on the hypertensive and renal response to ET-1 in anesthetized Sprague-Dawley rats. Acute intravenous infusion of ET-1 (10 pmol·kg-1·min-1) for 60 min significantly increased mean arterial pressure (MAP) from 125 ± 8 to 145 ± 8 mmHg (P < 0.05) and significantly decreased glomerular filtration rate (GFR) from 0.31 ± 0.09 to 0.13 ± 0.05 ml·min-1· 100 g kidney wt-1. Pretreatment with enalapril (10 mg/kg iv) before ET-1 infusion inhibited the increase in MAP (121 ± 4 vs. 126 ± 4 mmHg) before and during ET-1 infusion, respectively (P < 0.05) without blocking the effect of ET-1 on GFR. In contrast, neither omapatrilat (30 mg/kg) nor candesartan (10 mg/kg) had any effect on ET-1-induced increases in MAP or decreases in GFR. To determine whether the effect of enalapril was due to the decrease in angiotensin II or increase in kinin formation, rats were given REF-000359 (1 mg/kg iv), a selective B2 receptor antagonist, with or without enalapril before ET-1 infusion. REF-000359 completely blocked the effect of enalapril on ET-1 infusion (MAP was 117 ± 5 vs. 135 ± 5 mmHg before and during ET-1 infusion, respectively, P < 0.05). REF-000359 alone had no effect on the response to ET-1 infusion (MAP was 117 ± 4 vs. 144 ± 4 mmHg before and during ET-1 infusion, respectively, P < 0.05). REF-000359 with or without enalapril had no significant effect on the ability of ET-1 infusion to decrease GFR. These findings support the hypothesis that decreased catabolism of bradykinin and its subsequent vasodilator activity oppose the actions of ET-1 to increase MAP.
AB - Recent studies have shown that angiotensin-converting enzyme (ACE) inhibitors attenuate endothelin-1 (ET-1)-induced hypertension, but the mechanisms for this effect have not been clarified. Initial experiments were conducted to contrast the effect of the ACE inhibitor enalapril, the combined ACE-neutral endopeptidase inhibitor omapatrilat, and the angiotensin II receptor antagonist candesartan on the hypertensive and renal response to ET-1 in anesthetized Sprague-Dawley rats. Acute intravenous infusion of ET-1 (10 pmol·kg-1·min-1) for 60 min significantly increased mean arterial pressure (MAP) from 125 ± 8 to 145 ± 8 mmHg (P < 0.05) and significantly decreased glomerular filtration rate (GFR) from 0.31 ± 0.09 to 0.13 ± 0.05 ml·min-1· 100 g kidney wt-1. Pretreatment with enalapril (10 mg/kg iv) before ET-1 infusion inhibited the increase in MAP (121 ± 4 vs. 126 ± 4 mmHg) before and during ET-1 infusion, respectively (P < 0.05) without blocking the effect of ET-1 on GFR. In contrast, neither omapatrilat (30 mg/kg) nor candesartan (10 mg/kg) had any effect on ET-1-induced increases in MAP or decreases in GFR. To determine whether the effect of enalapril was due to the decrease in angiotensin II or increase in kinin formation, rats were given REF-000359 (1 mg/kg iv), a selective B2 receptor antagonist, with or without enalapril before ET-1 infusion. REF-000359 completely blocked the effect of enalapril on ET-1 infusion (MAP was 117 ± 5 vs. 135 ± 5 mmHg before and during ET-1 infusion, respectively, P < 0.05). REF-000359 alone had no effect on the response to ET-1 infusion (MAP was 117 ± 4 vs. 144 ± 4 mmHg before and during ET-1 infusion, respectively, P < 0.05). REF-000359 with or without enalapril had no significant effect on the ability of ET-1 infusion to decrease GFR. These findings support the hypothesis that decreased catabolism of bradykinin and its subsequent vasodilator activity oppose the actions of ET-1 to increase MAP.
KW - Angiotensin-converting enzyme inhibitors
KW - Blood pressure
KW - Bradykinin receptors
KW - Endothelin
KW - Glomerular filtration rate
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U2 - 10.1152/ajpheart.00027.2003
DO - 10.1152/ajpheart.00027.2003
M3 - Article
C2 - 12574005
AN - SCOPUS:0037686699
SN - 0363-6135
VL - 284
SP - H1899-H1903
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 6 53-6
ER -