title: Cardiovascular effects of inhibition of renin-angiotensin-aldosterone system components in hypertensive rats given salt excess.
abstract: This study examined the role of the renin-angiotensin-aldosterone system (RAAS) in mediating cardiovascular and renal damage in spontaneously hypertensive rats (SHR) given salt excess. Since the circulating RAAS is inhibited in this model, it permits examination of the role of local tissue RAASs in mediating this injury. To this end, male 8-wk SHR were divided into 7 groups. The control group (C) received normal NaCl (0.6%) diet. All other groups were given 8% NaCl chow. In addition, group 2 was given placebo, group 3 the mineralocorticoid receptor blocker eplerenone (100 mg.kg(-1).day(-1)), group 4 the angiotensin converting enzyme inhibitor quinapril (3 mg.kg(-1).day(-1)), group 5 the angiotensin II type 1 receptor blocker candesartan (10 mg.kg(-1).day(-1)), and groups 6 and 7 eplerenone and either quinapril or candesartan. The treatments lasted 8 wk. Compared with controls, mean arterial pressure (MAP), renal blood flow, coronary flow reserve, minimal coronary vascular resistance, diastolic time constant, and maximal rate of ventricular pressure fall were all adversely affected by salt loading. Left ventricular mass and fibrosis as well as proteinuria were also markedly increased by salt overload. Eplerenone induced only slight changes, whereas quinapril and candesartan normalized all indexes except MAP. Combination therapy also normalized all indexes, including MAP. These data suggest that 1) cardiovascular and renal damage induced by salt excess in the SHR were not pressure dependent; 2) mineralocorticoids were only marginally involved in this model; and 3) local tissue generation of angiotensin II may be, at least in part, responsible for the other adverse effects.
authors.affiliation: Ochsner Clinic Foundation, New Orleans, LA 70121, USA. dsusic@ochsner.org
authors.forename: Dinko
authors.initials: D
authors.lastname: Susic
authors.forename: Jasmina
authors.initials: J
authors.lastname: Varagic
authors.forename: Edward D
authors.initials: ED
authors.lastname: Frohlich
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced / Q000473:pathology; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology*; D000077545:Eplerenone; D006973:Hypertension / Q000503:physiopathology*; D006984:Hypertrophy / Q000139:chemically induced / Q000473:pathology; D007668:Kidney / Q000098:blood supply; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D000077583:Quinapril; D051381:Rats; D011918:Rats, Inbred SHR; D018161:Receptors, Mineralocorticoid / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology*; D017673:Sodium Chloride, Dietary / Q000009:adverse effects / Q000494:pharmacology*; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D044005:Tetrahydroisoquinolines / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D017673:Sodium Chloride, Dietary; D044005:Tetrahydroisoquinolines; D013777:Tetrazoles; D013148:Spironolactone; D000077545:Eplerenone; D000077583:Quinapril; C081643:candesartan