L-arginine-induced glomerular hyperfiltration response: the roles of insulin and ANG II.
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.
Ruiz
Mario
M
Division of Nephrology-Hypertension, VA San Diego Healthcare System and the University of California, San Diego School of Medicine, La Jolla, CA 92161, USA.
Singh
Prabhleen
P
Thomson
Scott C
SC
Munger
Karen
K
Blantz
Roland C
RC
Gabbai
Francis B
FB
D000804:Angiotensin II / Q000097:blood / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D005919:Glomerular Filtration Rate; D006400:Hematocrit; D007328:Insulin / Q000097:blood / Q000502:physiology*; D007678:Kidney Glomerulus / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009399:Nephrons / Q000187:drug effects / Q000378:metabolism; D009566:Nitrates / Q000097:blood / Q000652:urine; D009569:Nitric Oxide / Q000652:urine; D015282:Octreotide / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D007328:Insulin; D009566:Nitrates; D000804:Angiotensin II; D009569:Nitric Oxide; D001120:Arginine; D015282:Octreotide