期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 294, 期 5, 页码 R1744-R1751出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00871.2007
关键词
nitric oxide; glomerular filtration rate; octreotide
类别
资金
- NIDDK NIH HHS [R01 DK028602, R01 DK056248, DK 62831, DK 56248, DK 28602, K08 DK084305] Funding Source: Medline
Infusion of L-arginine produces an increase in glomerular filtration via kidney vasodilation, correlating with increased kidney excretion of nitric oxide (NO) metabolites, but the specific underlying mechanisms are unknown. We utilized clearance and micropuncture techniques to examine the whole kidney glomerular filtration rate (GFR) and single nephron GFR (SNGFR) responses to 1) L-arginine (ARG), 2) ARG + octreotide (OCT) to block insulin release, 3) ARG + OCT + insulin (INS) infusion to duplicate ARG-induced insulin levels, and 4) losartan (LOS), an angiotensin AT-1 receptor blocker, +ARG+OCT. ARG infusion increased GFR, while increasing insulin levels. OCT coinfusion prevented this increase in GFR, but with insulin infusion to duplicate ARG induced rise in insulin, the GFR response was restored. Identical insulin levels in the absence of ARG had no effect on GFR. In contrast to ARG infusion alone, coinfusion of OCT with ARG reduced proximal tubular fractional and absolute reabsorption potentially activating tubuloglomerular feedback. Losartan infusion, in addition to ARG and OCT (LOS+ARG+OCT), restored the increase in both SNGFR and proximal tubular reabsorption, without increasing insulin levels. In conclusion, 1) hyperfiltration responses to ARG require the concurrent, modest, permissive increase in insulin; 2) inhibition of insulin release after ARG reduces proximal reabsorption and prevents the hyperfiltration response; and 3) inhibition of ANG II activity restores the hyperfiltration response, maintains parallel increases in proximal reabsorption, and overrides the arginine/octreotide actions.
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