PMID: 7536100Jan 1, 1995Paper

IGF-I stimulates renal function in the isolated rat kidney: inhibition by aminoguanidine and nitroarginine methyl ester

Experimental Nephrology
I McKillopA M el Nahas

Abstract

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 t...Continue Reading

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