TY - JOUR
T1 - Nitric oxide in afferent arterioles after uninephrectomy depends on extracellular L-arginine
AU - Helle, Frank
AU - Skogstrand, Trude
AU - Schwartz, Idit F.
AU - Schwartz, Doron
AU - Iversen, Bjarne M.
AU - Palm, Fredrik
AU - Hultström, Michael
PY - 2013
Y1 - 2013
N2 - Uninephrectomy (UNX) causes hyperperfusion of the contralateral remaining kidney via increased nitric oxide (NO) synthesis. Although the exact mechanism remains largely unknown, we hypothesize that this would be localized to the afferent arteriole and that it depends on cellular uptake of L-arginine. The experiments were performed in rats 2 days (early) or 6 wk (late) after UNX and compared with controls (Sham) to study acute and chronic effects on NO metabolism. Renal blood flow was increased after UNX (21 ± 2 ml·min_1·kg_1 in sham, 30 ± 3 in early, and 26 ± 1 in late, P < 0.05). NO inhibition with N^-nitro-L-arginine methyl ester hydrochloride (l-NAME) caused a greater increase in renal vascular resistance in early UNX compared with Sham and late UNX (138 ± 24 vs. 88 ± 10, and 84 ± 7%, P < 0.01). The lower limit of autoregulation was increased both in early and late UNX compared with Sham (P < 0.05). l-NAME did not affect the ANG II-induced contraction of isolated afferent arterioles (AA) from Sham. AA from early UNX displayed a more pronounced contraction in response to l-NAME (-57 ± 7 vs. -16 ± 7%, P < 0.05) and in the absence of L-arginine (-41 ± 4%, P < 0.05) compared with both late UNX and Sham. mRNA expression of endothelial NO synthase was reduced, whereas protein expression was unchanged. Cationic amino acid transporter-1 and -2 mRNA was increased, while protein was unaffected in isolated preglomerular resistance vessels. In conclusion, NO-dependent hyperperfusion of the remaining kidney in early UNX is associated with increased NO release from the afferent arteriole, which is highly dependent on extracellular L-arginine availability.
AB - Uninephrectomy (UNX) causes hyperperfusion of the contralateral remaining kidney via increased nitric oxide (NO) synthesis. Although the exact mechanism remains largely unknown, we hypothesize that this would be localized to the afferent arteriole and that it depends on cellular uptake of L-arginine. The experiments were performed in rats 2 days (early) or 6 wk (late) after UNX and compared with controls (Sham) to study acute and chronic effects on NO metabolism. Renal blood flow was increased after UNX (21 ± 2 ml·min_1·kg_1 in sham, 30 ± 3 in early, and 26 ± 1 in late, P < 0.05). NO inhibition with N^-nitro-L-arginine methyl ester hydrochloride (l-NAME) caused a greater increase in renal vascular resistance in early UNX compared with Sham and late UNX (138 ± 24 vs. 88 ± 10, and 84 ± 7%, P < 0.01). The lower limit of autoregulation was increased both in early and late UNX compared with Sham (P < 0.05). l-NAME did not affect the ANG II-induced contraction of isolated afferent arterioles (AA) from Sham. AA from early UNX displayed a more pronounced contraction in response to l-NAME (-57 ± 7 vs. -16 ± 7%, P < 0.05) and in the absence of L-arginine (-41 ± 4%, P < 0.05) compared with both late UNX and Sham. mRNA expression of endothelial NO synthase was reduced, whereas protein expression was unchanged. Cationic amino acid transporter-1 and -2 mRNA was increased, while protein was unaffected in isolated preglomerular resistance vessels. In conclusion, NO-dependent hyperperfusion of the remaining kidney in early UNX is associated with increased NO release from the afferent arteriole, which is highly dependent on extracellular L-arginine availability.
KW - Afferent arteriole
KW - L-arginine
KW - Uninephrectomy
UR - http://www.scopus.com/inward/record.url?scp=84878640556&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.00665.2011
DO - 10.1152/ajprenal.00665.2011
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C2 - 23408167
AN - SCOPUS:84878640556
SN - 1931-857X
VL - 304
SP - 1088
EP - 1098
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
IS - 8
ER -