Key result
Ramipril and L-158809 prevented cardiac remodeling and renal damage in DOCA-salt hypertensive mice lacking the Ren-2 gene, despite having no antihypertensive effect.
Why the study?
Does an ACE inhibitor or AT1 receptor antagonist prevent cardiac remodeling and renal damage in DOCA-salt hypertensive mice lacking the Ren-2 gene?
Does an ACE inhibitor or AT1 receptor antagonist prevent cardiac remodeling and renal damage in DOCA-salt hypertensive mice lacking the Ren-2 gene?
ACE inhibitors and AT1 antagonists exert beneficial effects on cardiac remodeling and renal damage in DOCA-salt hypertensive mice independently of blood pressure reduction.
Supports BP-independent cardiorenal protection by ACEi/ARBs in this model; hypothesis-generating, requires human validation before practice change.
We previously reported that inhibition of angiotensin-converting enzyme (ACE) prevented the hypertension and left ventricular hypertrophy induced by deoxycorticosterone acetate-salt (DOCA-salt) in 129/SvEvTac mice, which have 2 renin genes (Ren-1 and Ren-2). In the present study, we induced hypertension by uninephrectomy and DOCA-salt in mice having only the Ren-1 gene (C57BL/6J) and investigated the effect of an ACE inhibitor (ramipril, 4 mg. kg(-)(1). d(-)(1)) and an angiotensin type 1 (AT(1)) receptor antagonist (L-158809, 4 mg. kg(-)(1). d(-)(1)) on the development of hypertension, cardiac hypertrophy, and renal injury. After 4 weeks of treatment, systolic blood pressure in DOCA-salt mice was significantly increased (128+/-2 mm Hg) compared with controls (109+/-2 mm Hg) (P:<0.001), while plasma renin concentration was decreased by 97% (P:<0.001). DOCA-salt also induced left ventricular and renal hypertrophy and renal damage as manifested by proteinuria. Collagen content in the left ventricle and kidney was significantly higher in DOCA-salt mice (P:<0.001). Urinary albumin (P:<0.05) and proliferating cell nucleic antigen-positive cells in the tubules and interstitium of the renal cortex (P:<0.001) were significantly increased in the DOCA-salt group. Neither the ACE inhibitor nor the AT(1) antagonist had any antihypertensive effect; however, they partially prevented cardiac hypertrophy and completely inhibited left ventricular collagen deposition. In the kidney, both the ACE inhibitor and AT(1) antagonist partially reduced the increase in collagen but had no effect on hypertrophy. They also significantly prevented the effect of DOCA-salt on urinary albumin and proliferating cell nucleic antigen expression in the kidney. Despite the lack of an antihypertensive effect, both ACE inhibitor and AT(1) antagonist prevented cardiac remodeling and renal damage. Our results indicate that ACE inhibitors and AT(1) antagonists exert beneficial effects on the heart and kidney in DOCA-salt hypertensive mice independently of their effects on blood pressure.
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Peng et al. (2001) studied Deoxycorticosterone acetate-salt (DOCA-salt) induced hypertension. ACE inhibitor (ramipril) and AT1 receptor antagonist (L-158809) vs. Control was evaluated on Development of hypertension, cardiac hypertrophy, and renal injury. Ramipril and L-158809 prevented cardiac remodeling and renal damage in DOCA-salt hypertensive mice lacking the Ren-2 gene, despite having no antihypertensive effect.
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