Evaluation of renal function during intrarenal norepinephrine infusion in conscious rats

Previous studies have shown that intrarenal infusion of norepinephrine (NE) causes acute renal failure in anesthetized dogs and rats. We hypothesized that anesthesia prevents the kidney of escaping from the ischemic insult. In this paper, we report measurements of renal function parameters during acute as well as during chronic intrarenal NE infusion in conscious freely moving rats. Intrarenal NE application in doses of 4 and 36 micrograms/kg X h was performed via the suprarenal artery by means of subcutaneously implanted minipumps. During acute intrarenal NE infusion over a 2-hour period in anesthetized as well as conscious rats, renal blood flow (RBF) was determined by means of the pulsed Doppler flowmeter technique. During long-term NE administration for 5 days, glomerular filtration rate (GFR) was determined as clearance of 51Cr-EDTA and effective renal plasma flow (ERPF) as clearance of 125I-hippuric acid. Clearance measurements were performed on control day, and on the 1st and 4th day of intrarenal NE infusion; furthermore, on the 1st and 4th day after stopping the intrarenal NE infusion. Acute intrarenal administration of doses of NE higher than 12 micrograms/kg X h, in anesthetized rats immediately reduced RBF to zero levels. However, in conscious rats, neither acute nor chronic intrarenal NE application induced severe long-lasting reductions in GFR or RBF respectively ERPF at any dose of NE applied. Therefore, we conclude that no acute renal failure is induced during intrarenal NE infusion in conscious rats; this is probably due to protective neurogenic mechanisms which are relatively inactivated during pentobarbital anesthesia.