Beneficial cardiovascular actions of eplerenone in the spontaneously hypertensive rat.
BACKGROUND
Aldosterone has been implicated as a potential mediator of cardiac and vascular damage in a variety of disorders. This study examined the role of aldosterone and its interplay with the renin-angiotensin system in the pathogenesis of hypertension. To this end, the effects of the aldosterone antagonist eplerenone and the angiotensin converting enzyme inhibitor lisinopril on cardiovascular mass, myocardial collagen, and coronary circulation were examined in spontaneously hypertensive rats.


METHODS
Male, 22-week-old rats were randomly divided into 4 groups (12 in each). The control group received no treatment, the second group was given eplerenone (100 mg/kg/day), the third received lisinopril (3 mg/kg/day), and the fourth was given eplerenone and lisinopril. After 12 weeks of respective treatments, systemic and regional hemodynamics and cardiovascular mass indexes were measured in conscious instrumented rats.


RESULTS
Eplerenone decreased arterial pressure but did not affect left ventricular mass or hydroxyproline concentration (an estimate of collagen). It did, however, reduce minimal coronary vascular resistance and increased coronary flow reserve. Lisinopril decreased arterial pressure and ventricular mass but did not affect regional hemodynamics. The combination therapy produced synergistic effects.


CONCLUSIONS
Aldosterone antagonism improved coronary and systemic hemodynamics in adult spontaneously hypertensive rats but did not affect cardiovascular mass indexes. The finding that lisinopril and eplerenone decreased arterial pressure to the same extent but had different cardiovascular effects suggested that these effects might be pressure independent.
Susic
Dinko
D
Hypertension Research Laboratory, Division of Research, Ochsner Clinic Foundation, New Orleans, LA 70121, USA. dsusic@ochsner.org
Varagic
Jasmina
J
Ahn
Jwari
J
Matavelli
Luis C
LC
Frohlich
Edward D
ED
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects; D000077545:Eplerenone; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D017706:Lisinopril / Q000494:pharmacology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D013148:Spironolactone; D000077545:Eplerenone; D017706:Lisinopril