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Deleterious effects of inhibition of the renin-angiotensin system in neonatal rats
M Charbit1, M Déchaux, I Blazy
1Department of Physiology, C.H.U. Necker-Enfants Malades, Paris, France.
Insights
Inhibition of the renin-angiotensin system (RAS) in neonatal rats caused high mortality and reversible kidney failure. This highlights the critical postnatal role of the RAS in early life development.
Area of Science:
- Neonatal physiology
- Cardiovascular pharmacology
- Renal system development
Background:
- The renin-angiotensin system (RAS) is crucial for cardiovascular and renal homeostasis.
- Its role during the critical postnatal developmental period in mammals requires further elucidation.
Purpose of the Study:
- To investigate the effects of inhibiting the RAS in neonatal rats during the first two weeks of life.
- To assess the impact on blood pressure, renal function, and RAS components.
Main Methods:
- Neonatal rats were treated daily from birth to day 14 with an angiotensin I converting enzyme inhibitor (ACEI) perindopril, a vasodilator dihydralazine (DHL), or distilled water.
- Evaluations included blood pressure, plasma creatinine, plasma renin activity (PRA), substrate (PRS), renin concentration (PRC), and renal renin content on days 14 and 28.
Main Results:
- ACEI treatment led to high mortality, significant hypotension (57 mmHg vs. 103 mmHg in controls), and increased plasma creatinine by day 14.
- ACEI rats showed undetectable PRA and PRS, but increased PRC and renal renin staining.
- By day 28, blood pressure and plasma creatinine normalized in ACEI rats, with no significant differences in PRA, PRS, or PRC compared to controls.
Conclusions:
- The RAS plays a vital postnatal role in neonatal rats.
- Early-life RAS inhibition causes severe, but reversible, renal impairment and hypotension.
- Neonatal RAS inhibition results in a defect in circulating angiotensinogen.
Abstract:
The angiotensin I converting enzyme inhibitor (ACEI) perindopril (2 mg/kg body weight), the peripheral vasodilator dihydralazine (DHL) (25 mg/kg body weight) or distilled water was given daily from birth to day 14 to neonatal rats. Blood pressure, plasma creatinine, plasma renin activity (PRA), substrate (PRS) and concentration (PRC) and renin content of kidney tissue sections were evaluated on days 14 and 28. By day 14, a high mortality in the ACEI group was observed. ACEI, but not DHL, led to a significant fall (P < 0.01) in blood pressure, 57 +/- 11 versus 89 +/- 25 in the DHL group and 103 +/- 24 mmHg in controls, and to a dramatic increase in plasma creatinine. PRA and PRS were undetectable in ACEI-treated rats; in contrast, PRC and renal staining with anti-renin antibody were significantly increased in ACEI rats. On day 28, the blood pressure was normal in all groups and plasma creatinine returned to the normal range in ACEI rats. PRA, PRS and PRC were not significantly different in the ACEI group and controls. These results suggest that the renin-angiotensin system (RAS) plays a major postnatal role in the neonatal rat. Inhibition of the RAS during the first 2 weeks of life leads to high mortality, severe hypotension, reversible renal failure and a defect in circulating angiotensinogen.