The present study was performed to determine the influence of absence of angiotensin type 1A (AT(1A)) and/or AT(1B) receptor feedback regulation of kidney neuronal nitric oxide synthase (nNOS) and renin protein expression. Kidneys were harvested from wild-type (WT), AT(1A)(-/-), AT(1B)(-/-), and AT(1A)(-/-)AT(1B)(-/-) mice and immunostained for nNOS and renin protein localization. AT(1A)(-/-) and AT(1A)(-/-)AT(1B)(-/-) kidneys demonstrated an increase in the percentage of glomeruli with nNOS-positive afferent and interlobular arterioles compared with WT mice. Density of vascular nNOS immunostaining was 20-fold higher in kidneys of AT(1A)(-/-) and AT(1A)(-/-)AT(1B)(-/-) compared with WT mice. Density of macula densa nNOS immunostaining was 7-fold higher in AT(1A)(-/-)AT(1B)(-/-) than in WT mice. Percent of glomeruli positive for juxtaglomerular (JG) cell renin was 3-fold higher, whereas the density of JG cell renin immunostaining was 15-fold higher in kidneys of AT(1A)(-/-) and AT(1A)(-/-)AT(1B)(-/-) compared with WT mice. Kidneys of AT(1A)(-/-) and AT(1A)(-/-)AT(1B)(-/-) mice displayed recruitment of renin protein expression along afferent and interlobular arterioles. Absence of AT(1) receptor signaling resulted in enhanced nNOS protein expression in both microvascular and tubular structures. Enhanced NO generation may contribute to the reduced renal vascular tone and blood pressure observed with blockade of the renin-angiotensin system.
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| http://dx.doi.org/10.1369/jhc.2007.950220 | DOI Listing |
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