Published Online
on June 7, 2004

A more recent version of this article appeared on July 1, 2004

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Submitted on March 23, 2004
Revised on April 5, 2004

Perinatal L-Arginine and Antioxidant Supplements Reduce Adult Blood Pressure in Spontaneously Hypertensive Rats

Simona Racasan; Branko Braam; Dionne M. van der Giezen; Roel Goldschmeding; Peter Boer; Hein A. Koomans; and Jaap A. Joles^*

From the Departments of Nephrology and Hypertension (S.R., B.B., P.B., H.A.K., J.A.J.) and Pathology (D.M.v.d.G., R.G.), University Medical Center, Utrecht, The Netherlands.

^* To whom correspondence should be addressed. E-mail: J.A.Joles{at}med.uu.nl.

Abstract--Embryo cross-transplantation and cross-fostering between spontaneously hypertensive rats (SHR) and normotensive rats (WKY) suggest that perinatal environment modulates the genetically determined phenotype. In SHR the balance between NO and reactive oxygen species (ROS) is disturbed. We hypothesized that increasing NO and diminishing ROS in perinatal life would ameliorate hypertension in adult SHR. Pregnant SHR and WKY and their offspring received L-arginine plus antioxidants (vitamin C, vitamin E, and taurine) during the last 2 weeks of pregnancy and then until either 4 or 8 weeks after birth. Systolic blood pressure (SBP) and urinary excretion of protein, nitrates (NO_x), and thiobarbituric acid reactive substances (TBARS) were measured. At 48 weeks of age rats were euthanized for glomerular counts. Perinatal supplements reduced SBP persistently in SHR and prevented the SBP increase observed in aging WKY. Initially NO_x excretion was lower and TBARS excretion higher in SHR than WKY. There was a direct effect on NO_x excretion in supplemented pregnant SHR and their offspring, but no increase was observed after stopping the supplements. TBARS excretion was only depressed up to 14 weeks by the supplements despite persistent differences in SBP. Consistent effects on nephron number were absent. Mild proteinuria, present in control SHR at 48 weeks, was prevented in all supplemented rats. Perinatal supplementation of NO substrate and antioxidants results in persistent reduction of SBP and renal protection in SHR, although effects on NO_x and TBARS were only transient. This suggests a critical role for perinatal pro- and antioxidant balance in programming BP later in life.

Key words: diet • hypertension, renal • oxidative stress • nitric oxide

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