Eplerenone prevents salt-induced vascular remodeling and cardiac fibrosis in stroke-prone spontaneously hypertensive rats.
We examined the effect of different levels of salt intake on the role of aldosterone on cardiac and vascular changes in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Eleven-week-old SHRSP were fed high-salt (4.2% NaCl), normal-salt (0.28%), or low-salt (0.03%) diets with or without eplerenone (100 mg/kg per day, in food) for 5 weeks. A group of high-salt SHRSP was also treated with hydralazine (25 mg/kg per day). Blood pressure increased more in high-salt rats than in other groups (P<0.001). Eplerenone prevented further blood pressure rise in salt-loaded rats, with little effect on control and low-salt SHRSP. Increased media-to-lumen ratio of mesenteric resistance arteries induced by salt (P<0.01) was prevented by eplerenone (P<0.01). Maximal acetylcholine-induced vasodilation was impaired under salt loading (P<0.01), but improved under eplerenone (P<0.01). Eplerenone prevented (P<0.01) increased heart weight and left and right ventricular collagen deposition induced by high salt. Blood pressure lowering by hydralazine in high-salt SHRSP did not influence endothelial function or left ventricular collagen. Our study demonstrates salt-dependency of aldosterone effects on severity of hypertension, endothelial dysfunction, and cardiac and vascular remodeling in SHRSP. These effects were attenuated by eplerenone, particularly in the salt-loaded state, underlining the pathophysiological role of aldosterone in salt-sensitive hypertension.
Endemann
Dierk H
DH
CIHR Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Canada.
Touyz
Rhian M
RM
Iglarz
Marc
M
Savoia
Carmine
C
Schiffrin
Ernesto L
EL
D000109:Acetylcholine / Q000494:pharmacology; D000450:Aldosterone / Q000502:physiology*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D000077545:Eplerenone; D005355:Fibrosis; D006321:Heart / Q000187:drug effects*; D006830:Hydralazine / Q000627:therapeutic use; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000473:pathology; D000451:Mineralocorticoid Receptor Antagonists; D009206:Myocardium / Q000737:chemistry / Q000473:pathology*; D009318:Natriuresis / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000633:toxicity*; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D000975:Antioxidants; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D017673:Sodium Chloride, Dietary; D017392:Thiobarbituric Acid Reactive Substances; D006830:Hydralazine; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D003094:Collagen; D000109:Acetylcholine