Erythropoietin response to acute hypobaric or anaemic hypoxia in gentamicin-administered rats.
In an attempt to assess the erythropoietin (Epo) production site(s) in rat kidney, Epo response to hypoxia and renal histopathological changes were studied in rats administered with graded doses of gentamicin. Male Sprague-Dawley rats of 9 to 11 weeks old were used. Following a 14-day subcutaneous administration (67.5 or 33.8 mg kg-1 day-1) of gentamicin, a nephrotoxic aminoglycoside, selective proximal tubular lesions were produced. These gentamicin-administered rats were compared with normal rats with respect to Epo response to hypoxia. Two different kinds of hypoxic load, either 0.35 atm hypobaric hypoxia (PIO2 = 46 torr) or acute anaemia (Ht: 29.3 +/- 0.2% and [Hb]: 9.7 +/- 0.3 g dl-1) by withdrawing of blood corresponding to 1-2% of body weight was used. During the hypoxic period of up to 48 h, the peak renal venous plasma Epo titres of 3.1 +/- 0.6 and 4.3 +/- 0.6 U ml-1 was observed at the 6th h in normal hypobaric hypoxic and anaemic rats, compared with the prehypoxic value of 0.7 +/- 0.1 U ml-1. The Epo titres then declined gradually. In the rats which were administered gentamicin, Epo response pattern was the same as that observed in the normal rats, but the peak value decreased significantly to 0.8 +/- 0.3 and 1.1 +/- 0.4 U ml-1 in hypoxic and anaemic rats (P < 0.05). Histological examination revealed the selective damage to renal proximal convoluted tubules. The Epo response was reduced by the tissue damages, and restoration of the gentamicin-induced tissue injury was accompanied with restored Epo response to hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
Shimizu
S
S
Second Department of Physiology, Nara Medical University, Japan.
Enoki
Y
Y
Sakata
S
S
Kohzuki
H
H
Ohga
Y
Y
Matsumura
K
K
D000740:Anemia / Q000378:metabolism; D000818:Animals; D001274:Atmospheric Pressure; D001810:Blood Volume; D004921:Erythropoietin / Q000096:biosynthesis*; D005839:Gentamicins / Q000633:toxicity*; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010953:Plasma Volume; D051381:Rats; D017207:Rats, Sprague-Dawley
D005839:Gentamicins; D004921:Erythropoietin