Abstract
The low GFR of newborns is maintained by various factors including the renin-angiotensin system. We previously established the importance of angiotensin II in the newborn kidney, using the angiotensin-converting enzyme inhibitor perindoprilat. The present study was designed to complement these observations by evaluating the role of angiotensin-type 1 (AT1) receptors, using losartan, a specific AT1-receptor blocker. Increasing doses of losartan were infused into anesthetized, ventilated, newborn rabbits. Renal function and hemodynamic variables were assessed using inulin and para-aminohippuric acid clearances as markers of GFR and renal plasma flow, respectively. Losartan 0.1 mg/kg slightly decreased mean blood pressure (−11%) and increased diuresis (+22%). These changes can be explained by inhibition of the AT1-mediated vasoconstrictive and antidiuretic effects of angiotensin, and activation of vasodilating and diuretic AT2 receptors widely expressed in the neonatal period. GFR and renal blood flow were not modified. Losartan 0.3 mg/kg decreased mean blood pressure significantly (−15%), probably by inhibiting systemic AT1 receptors. GFR significantly decreased (−25%), whereas renal blood flow remained stable. The decrease in filtration fraction (−21%) indicates predominant efferent vasodilation. At 3 mg/kg, the systemic hypotensive effect of losartan was marked (mean blood pressure, −28%), with decreased GFR and renal blood flow (−57% and −51%, respectively), a stable filtration fraction, and an increase in renal vascular resistance by 124%. The renal response to this dose can be considered as reflex vasoconstriction of afferent and efferent arterioles, rather than specific receptor antagonism. We conclude that under physiologic conditions, the renin-angiotensin is critically involved in the maintenance of GFR in the immature kidney.
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Abbreviations
- AII:
-
angiotensin II
- ACE:
-
angiotensin-converting enzyme
- ARI:
-
acute renal insufficiency
- AT1:
-
angiotensin type 1 receptor
- AT2:
-
angiotensin type 2 receptor
- BK:
-
bradykinin
- BW:
-
body weight
- EFP:
-
effective filtration pressure
- FF:
-
filtration fraction
- GFR:
-
glomerular filtration rate
- NO:
-
nitric oxide
- PAH:
-
para-aminohippuric acid
- RAS:
-
renin-angiotensin system
- RBF:
-
renal blood flow
- RVR:
-
renal vascular resistance
- UV:
-
urine flow rate
- UVNa:
-
urinary excretion of sodium
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Acknowledgements
The authors thank M. Thonney Viani and M. Julita for skillful technical help and their valuable contributions in the laboratory. Dr. Peter Toth-Heyn gave valuable advice that was greatly appreciated.
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Supported by the Swiss National Science Foundation, grant no. 3200-052463.97/1.
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Prévot, A., Mosig, D. & Guignard, JP. The Effects of Losartan on Renal Function in the Newborn Rabbit. Pediatr Res 51, 728–732 (2002). https://doi.org/10.1203/00006450-200206000-00011
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DOI: https://doi.org/10.1203/00006450-200206000-00011
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