Key result
Reduced nephron number dose was exponentially correlated with increased systolic blood pressure, LV hypertrophy, and dysfunction (P<0.0001), while ramipril provided strong cardiorenal protection.
Why the study?
Does ACE inhibition with ramipril improve cardiorenal damage in rat models with reduced nephron number?
Does ACE inhibition with ramipril improve cardiorenal damage in rat models with reduced nephron number?
Reduced nephron number is an independent determinant of blood pressure and cardiorenal damage in rats, which can be mitigated by ACE inhibition with ramipril.
Answers are grounded in this paper and cite their sources.
Ramipril attenuates cardiorenal injury in reduced-nephron rat models; leaves open translation to human hypertension and LV dysfunction.
BACKGROUND: Low nephron number is a recently identified cause of arterial hypertension. We set out to test the effect of nephron number dosing on blood pressure and cardiorenal damage including left ventricular (LV) remodeling and function. Because exact determination of nephron number in vivo is currently not possible, we combined the Munich Wistar Frömter (MWF) genetic rat model of inborn nephron deficit with the 5/6 renal ablation model (Nx). METHODS: To obtain distinct levels of nephron number dose (NND), rats underwent either sham-operation (Wistar-Sham NND 1.0, and MWF-Sham NND 0.6, n = 15, respectively) or 5/6 renal ablation (Nx, Wistar-Nx NND 0.17, and MWF-Nx NND 0.1, n = 20, respectively). Two additional groups were treated orally for 4 weeks with 1 mg/kg/day ramipril (Wistar-Nx-ACEI and MWF-Nx-ACEI, n = 15, respectively). RESULTS: Systolic blood pressure (SBP), LV hypertrophy, mRNA expression of atrial natriuretic factor, LV contractility, and relaxation were exponentially correlated with NND (P < 0.0001, respectively). Creatinine clearance (Cl(Cr)) decreased, albuminuria, renal interstitial fibrosis, tubulointerstitial damage, and glomerulosclerosis index increased with lowering NND in both Wistar-Nx (NND 0.17) and MWF-Nx (NND 0.1) animals. LV perivascular and interstitial fibrosis and sarcoplasmic reticular (SR) Ca(2+) cycling were not directly related to NND. Angiotensin-converting enzyme (ACE) inhibition with ramipril demonstrated strong cardio- and renoprotective effects even in the setting of very low NND of 0.1 in MWF-Nx animals. CONCLUSIONS: These data demonstrate that reduced nephron number is a significant, independent determinant of blood pressure, cardiorenal damage, and LV dysfunction in a direct dose-dependent way.
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Rothermund et al. (2010) studied Arterial hypertension and cardiorenal damage (n=100). Nephron number dosing (NND) and ramipril vs. Sham-operation (higher NND) was evaluated on Systolic blood pressure, LV hypertrophy, mRNA expression of atrial natriuretic factor, LV contractility, and relaxation (p=<0.0001). Reduced nephron number dose was exponentially correlated with increased systolic blood pressure, LV hypertrophy, and dysfunction (P<0.0001), while ramipril provided strong cardiorenal protection.
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