Jens Randel Nyengaard

Perinatal blockade of angiotensin (AT1) receptors causes fewer glomeruli and hypertension in adulthood

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The renin-angiotensin system (RAS) is known to be important for normal renal development, but the long-term implications of a suppressed RAS during the perinatal period are not known. This study tested the hypothesis that the perinatal RAS plays an important role in regulation of arterial pressure in adulthood. Sprague-Dawley rat pups were treated with the AT1 receptor antagonist losartan (25 mg/kg/d, s.c.) for the first 12 d of life (LOS). Vehicle-treated gender-matched littermates were used as controls (CON). At ∼21 wks the rats were chronically instrumented for measurement of arterial pressure. Total glomerular number was then determined using the disector method. CON LOS Glomerular number (per kidney) 26,111 ± 2,004 15,325 ± 959* Glomerular volume (106 μ3) 1.48 ± 0.07 1.44 ± 0.15 Mean arterial pressure (mmHg) 120 ± 1 134 ± 3 * (*p<0.05) These data indicate that the perinatal AT1 receptor is important, in "programming" for total number of nephrons and arterial pressure in adulthood. Physiological conditions causing suppression of the RAS in the developing animal may thus have long-term consequences for arterial pressure, possibly by limiting the number of nephrons that develop.

Original languageEnglish
JournalFASEB Journal
Publication statusPublished - 20 Mar 1998

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