Effects of gentamicin on glomerular renin release.
Gentamicin nephrotoxicity is associated with impaired glomerular function. To examine whether the effects of gentamicin on glomerular function are mediated through alterations in the renal-angiotensin system, basal and stimulated glomerular renin release was assessed in isolated glomeruli from control and gentamicin-treated rats. Male Sprague-Dawley rats (220 +/- 20 g) were studied immediately after treatment with gentamicin sulfate (4 mg/kg BW/day, n = 6) for 1 or 2 consecutive weeks and after 1 week of recovery from 2 weeks of treatment. Control rats received an equivalent volume of saline (n = 9). After the respective treatment, renal renin content was measured. In addition, glomeruli from control and gentamicin-treated rats were isolated and glomerular renin release was measured under basal conditions and after stimulation with the calmodulin inhibitor trifluoperazine (1 x 10(-4) M). Renin concentration was determined in aliquots of the supernatant by measuring the generation of angiotensin I using radioimmunoassay techniques at 15-min intervals. Renal renin content was significantly increased after 2 weeks of gentamicin treatment (+47%) and remained elevated (+62%) 1 week after discontinuing a 2-week gentamicin treatment. Both basal and stimulated glomerular renin release were lower in glomeruli isolated from gentamicin-treated rats. The effect of gentamicin added in vitro to glomeruli isolated from untreated rats was also evaluated. Exposure of normal glomeruli to in vitro gentamicin (1 mM) resulted in a significant inhibition of both basal (-47%, p < .05) and stimulated (-84%, p < .05) glomerular renin release. To determine whether the inhibitory action of gentamicin on glomerular renin release was dependent on extracellular calcium concentration, the effects of gentamicin on glomerular renin release were also assessed in the absence of extracellular calcium. Our data revealed that in the absence of extracellular calcium, the inhibitory effect of gentamicin on both basal and stimulated glomerular renin release was abolished. Taken together, these findings strongly suggest an inhibitory effect of gentamicin on glomerular renin release. Furthermore, the inhibition of glomerular renin release induced by gentamicin appears to be dependent on extracellular calcium.
Fernández-Repollet
E
E
Department of Pharmacology, University of Puerto Rico Medical Sciences Campus, San Juan 00936.
Fantauzzi
R
R
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000201:enzymology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005839:Gentamicins / Q000009:adverse effects*; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D000092502:Renin Inhibitors
D002118:Calcium; D005839:Gentamicins; D012083:Renin; D000092502:Renin Inhibitors