The effects of losartan on renal function in the newborn rabbit.

Details

Serval ID
serval:BIB_F333F83873EE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The effects of losartan on renal function in the newborn rabbit.
Journal
Pediatric Research
Author(s)
Prevot A., Mosig D., Guignard J.P.
ISSN
0031-3998
Publication state
Published
Issued date
2002
Peer-reviewed
Oui
Volume
51
Number
6
Pages
728-732
Language
english
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 (AT(1)) receptors, using losartan, a specific AT(1)-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 AT(1)-mediated vasoconstrictive and antidiuretic effects of angiotensin, and activation of vasodilating and diuretic AT(2) 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 AT(1) 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.
Keywords
Animals, Animals, Newborn, Antihypertensive Agents/pharmacology, Blood Pressure/drug effects, Blood Proteins, Carbon Dioxide/blood, Glomerular Filtration Rate/drug effects, Heart Rate/drug effects, Hematocrit, Losartan/pharmacology, Oxygen/blood, Rabbits, Receptor, Angiotensin, Type 1, Receptors, Angiotensin/antagonists & inhibitors
Pubmed
Web of science
Create date
20/07/2009 14:17
Last modification date
20/08/2019 17:20
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