IGF-I stimulates renal function in the isolated rat kidney: inhibition by aminoguanidine and nitroarginine methyl ester.
IGF-I is known to increase renal function when administered in vivo. To establish whether IGF-I has a direct effect on renal function, the present experiments were performed to measure the effects of IGF-I in the isolated perfused rat kidney (IPRK). We have examined the influence of l-nitroarginine methyl ester (l-NAME), a non-selective inhibitor of nitric oxide synthase (NOS) and aminoguanidine (AG), a selective inhibitor of the inducible isoform of NOS on the direct effects of recombinant human IGF-I (rhIGF-I) on renal function in the IPRK. rhIGF-I (100 nM) increased both glomerular filtration rate (GFR) (+109 +/- 17%, n = 6, p < 0.01) and renal perfusate flow (RPF) (+100 +/- 15%, n = 6, p < 0.01), effects which were completely blocked by l-NAME (10 microM). In the presence of the enantiomer d-NAME (10 microM, n = 6) which is not an inhibitor of NOS, rhIGF-I (100 nM) still produced a significant increase in both GFR (+175 +/- 15%, n = 6, p < 0.01) and RPF (+94 +/- 7%, n = 6, p < 0.01). AG blunted the renal haemodynamic response to rhIGF-I (GFR +49 +/- 10, RPF + 31 +/- 7, n = 6, p < 0.05), but unlike l-NAME, did not abolish it. The haemodynamic responses of the IPRK to rhIGF-I in the presence of AG were significantly greater than those of rhIGF-I in the presence of l-NAME (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
McKillop
I
I
Sheffield Kidney Institute, Northern General Hospital, UK.
Haylor
J
J
el Nahas
A M
AM
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006146:Guanidines / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D006146:Guanidines; D007334:Insulin-Like Growth Factor I; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester