Abstract:
:We assessed the contribution of angiotensin-(1-7) [Ang-(1-7)] to captopril-induced cardiovascular protection in spontaneously hypertensive rats (SHRs) chronically treated with the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (SHR-l). NG-nitro-L-arginine methyl ester (80 mg/L) administration for 3 weeks increased mean arterial pressure (MAP) from 196 ± 6 to 229 ± 3 mm Hg (P < 0.05). Treatment of SHR-l with Ang-(1-7) antagonist [d-Ala7]-Ang-(1-7) (A779; 744 μg·kg(-1)·d(-1) ip) further elevated MAP to 253 ± 6 mm Hg (P < 0.05 vs SHR-l or SHR). Moreover, A779 treatment attenuated the reduction in MAP and proteinuria by either captopril (300 mg/L in drinking water) or hydralazine (1.5 mg·kg(-1)·d(-1) ip). In isolated perfused hearts, the recovery of left ventricular function from global ischemia was enhanced by captopril or hydralazine treatment and was exacerbated with A779. The Ang-(1-7) antagonist attenuated the beneficial effects of captopril and hydralazine on cardiac function. Recovery from global ischemia was also improved in isolated SHR-l hearts acutely perfused with captopril during both the perfusion and reperfusion periods. The acute administration of A779 reduced the beneficial actions of captopril to improve recovery after ischemia. We conclude that during periods of reduced nitric oxide availability, endogenous Ang-(1-7) plays a protective role in effectively buffering the increase in blood pressure and renal injury and the recovery from cardiac ischemia. Moreover, Ang-(1-7) contributes to the blood pressure lowering and tissue protective actions of captopril and hydralazine in a model of severe hypertension and end-organ damage.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Benter IF,Yousif MH,Al-Saleh FM,Raghupathy R,Chappell MC,Diz DIdoi
10.1097/FJC.0b013e31821324b6subject
Has Abstractpub_date
2011-05-01 00:00:00pages
559-67issue
5eissn
0160-2446issn
1533-4023journal_volume
57pub_type
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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更新日期:1987-01-01 00:00:00