title: Angiotensin-(1-7) blockade attenuates captopril- or hydralazine-induced cardiovascular protection in spontaneously hypertensive rats treated with NG-nitro-L-arginine methyl ester.
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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait.
authors.forename: Ibrahim F
authors.initials: IF
authors.lastname: Benter
authors.forename: Mariam H M
authors.initials: MH
authors.lastname: Yousif
authors.forename: Fatemah M
authors.initials: FM
authors.lastname: Al-Saleh
authors.forename: Raj
authors.initials: R
authors.lastname: Raghupathy
authors.forename: Mark C
authors.initials: MC
authors.lastname: Chappell
authors.forename: Debra I
authors.initials: DI
authors.lastname: Diz
mesh_terms: D000803:Angiotensin I / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000804:Angiotensin II / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000276:immunology; D006321:Heart / Q000187:drug effects*; D006830:Hydralazine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010477:Perfusion; D011507:Proteinuria / Q000517:prevention & control / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: C092006:7-Ala-angiotensin (1-7); D000959:Antihypertensive Agents; D001786:Blood Glucose; D016207:Cytokines; D007328:Insulin; D020738:Leptin; D010446:Peptide Fragments; D000804:Angiotensin II; D006830:Hydralazine; D000803:Angiotensin I; D002216:Captopril; C118790:angiotensin I (1-7); D019331:NG-Nitroarginine Methyl Ester