0300-9629p2 $5.00 5 0.00 Q 1992 Fe’ergamon Press Lid
URATE EXCRETION BY THE CAT K‘IDNEY YONG KEUN KIM,* DCING K~CIN JUNG, JIN SUP JUNG and SANC Ha LEE Department of Physiology, College of Medicine, Pusan National University, Pusan, 602-734, Korea
Abstract-
1. The renal handling of urate by the cat kidney was investigated during continuous infusion
of urate. 2. Fractional irate excretion (FE,) in cats was Q.57 f. 0.04, indicating net reabsarptjon of urate. In in rabbits was 1.76 r~.0.08, reflecting net secretion of urate. FE,, 3. Fractional PAtll excretion OT$,H) was 3.94 k 0.26 in cats and 4.12 & 0.76 in rabbits, showing net secretion in both species. 4. FE,, in cats was dependent on urine flow, but was jndep~ndent of plasma urate concentration. 5. The urrte excretion in cats was enhanced by probenecid, but was insensitive to PAH and PZA. 6. The PAH excretion in cats was reduced by probenecid, but was unaltered by uratc and PZA. 7. These resuIt$ indicate that urate is Ran&c! in the cat kidney by a unique transport system which is distinct from that for organic anions.
contrast,
Num~rons studies have demonstrated that the renal handfing of urate is characterized by the existence 5f considerable species variations (Mudge et ai., 1973). In most species, urate is almost freely filtered at the ~fomer~lus with minimal protein binding (Farreff et al,, 1971; Roth-Ran& and Peters. 1978) and transported bidirectionalfy by a ~arrf~~-mediated mechanism in the renal proximal tubule (M~rfler and Sheikh, 1983). Thus, urate appearing in the final urine reflects a complex modification of filtrate, involving both tubular secretion and reabsorption. However, the relative ~ont~~bntjon of the reabsarptive and secretory components varies widely from species to species. Since urate exists as an anion at a normal plasma pN, it is anticipated to be handied by the organic anion transport system. Accordingfy, the relationship between urate and p-aminohippurate (PAH) secretion has been investigated in various species. It has been shown that urate and PAH are secreted by a common transport mechanism in some species, and by different mechanisms in other species (WC review oE Msffer and Sheikh, 1983). Probenecid enhances usate excretion in man and nonhuman primates (Nudge et al., 1973), whereas it reduces urate excretion in the species with net urate secretion, such as rabbits (Donoson and Grantham, 1986), Dalmatian dogs (Kessler et aI., 19591, guinea pigs &fudge er ail.? 1968b) and pigs (Simmonds et a& 1976). Pyrazinoic acid (PZA) inhibits m-ate secretion in men, dogs and rats, but not in rabbits and pigs (Weiner, 1985). However, the effects of thesedrugs on the urate excretion in cats have not been determine& The present study was therefore undertaken to characterize the re~raf handting of watt in the cat. For comparison, renal excretion of PAH was also examined.
Cats (2-3 kg) and New Zealand White rabbits (1 .S-2.5 kg) aT both sexes were used. Cats wee anesthetized with ~~~~~t~tal sodium (25 mglkg) by intravenous injection, and rabbits with a mixture of ketamine (25 m&kg) and xyiazine (5 me/kg) by intramuscular injection. After cannufation of the trachea, a polyethylene catheter was introduced into the carotid artery for recording of blood pressure and for blood sampling. The femoral vein (the ear vein in the rabbit) was catheterized for infusion of solutions. The bladder was catheterized through a suptapubic incision for urine sampling. Isotonic saline (4Oml) was given intravenQusty to replace blood loss and perspiration during the operation. After cumpietion of surgical procedures, priming doses of inulin (5 mg!kg) and urate (5 q/kg) were injected and followed by sustaining infusion of saline contaming inulin (5 mg/ml) and urate(0.5mg/ml) at a rate OF 1ml/min, The sustaining infusion was continued to the end of experiment. After an equilibrium period of approximately 40min, three 10.min collection periods were made to determine the control urate clearance, after which a bolus of
PAH (60 mg:k@, probenecid
URATE EXCRETION BY THE CAT K‘IDNEY YONG KEUN KIM,* DCING K~CIN JUNG, JIN SUP JUNG and SANC Ha LEE Department of Physiology, College of Medicine, Pusan National University, Pusan, 602-734, Korea
Abstract-
1. The renal handling of urate by the cat kidney was investigated during continuous infusion
of urate. 2. Fractional irate excretion (FE,) in cats was Q.57 f. 0.04, indicating net reabsarptjon of urate. In in rabbits was 1.76 r~.0.08, reflecting net secretion of urate. FE,, 3. Fractional PAtll excretion OT$,H) was 3.94 k 0.26 in cats and 4.12 & 0.76 in rabbits, showing net secretion in both species. 4. FE,, in cats was dependent on urine flow, but was jndep~ndent of plasma urate concentration. 5. The urrte excretion in cats was enhanced by probenecid, but was insensitive to PAH and PZA. 6. The PAH excretion in cats was reduced by probenecid, but was unaltered by uratc and PZA. 7. These resuIt$ indicate that urate is Ran&c! in the cat kidney by a unique transport system which is distinct from that for organic anions.
contrast,
Num~rons studies have demonstrated that the renal handfing of urate is characterized by the existence 5f considerable species variations (Mudge et ai., 1973). In most species, urate is almost freely filtered at the ~fomer~lus with minimal protein binding (Farreff et al,, 1971; Roth-Ran& and Peters. 1978) and transported bidirectionalfy by a ~arrf~~-mediated mechanism in the renal proximal tubule (M~rfler and Sheikh, 1983). Thus, urate appearing in the final urine reflects a complex modification of filtrate, involving both tubular secretion and reabsorption. However, the relative ~ont~~bntjon of the reabsarptive and secretory components varies widely from species to species. Since urate exists as an anion at a normal plasma pN, it is anticipated to be handied by the organic anion transport system. Accordingfy, the relationship between urate and p-aminohippurate (PAH) secretion has been investigated in various species. It has been shown that urate and PAH are secreted by a common transport mechanism in some species, and by different mechanisms in other species (WC review oE Msffer and Sheikh, 1983). Probenecid enhances usate excretion in man and nonhuman primates (Nudge et al., 1973), whereas it reduces urate excretion in the species with net urate secretion, such as rabbits (Donoson and Grantham, 1986), Dalmatian dogs (Kessler et aI., 19591, guinea pigs &fudge er ail.? 1968b) and pigs (Simmonds et a& 1976). Pyrazinoic acid (PZA) inhibits m-ate secretion in men, dogs and rats, but not in rabbits and pigs (Weiner, 1985). However, the effects of thesedrugs on the urate excretion in cats have not been determine& The present study was therefore undertaken to characterize the re~raf handting of watt in the cat. For comparison, renal excretion of PAH was also examined.
Cats (2-3 kg) and New Zealand White rabbits (1 .S-2.5 kg) aT both sexes were used. Cats wee anesthetized with ~~~~~t~tal sodium (25 mglkg) by intravenous injection, and rabbits with a mixture of ketamine (25 m&kg) and xyiazine (5 me/kg) by intramuscular injection. After cannufation of the trachea, a polyethylene catheter was introduced into the carotid artery for recording of blood pressure and for blood sampling. The femoral vein (the ear vein in the rabbit) was catheterized for infusion of solutions. The bladder was catheterized through a suptapubic incision for urine sampling. Isotonic saline (4Oml) was given intravenQusty to replace blood loss and perspiration during the operation. After cumpietion of surgical procedures, priming doses of inulin (5 mg!kg) and urate (5 q/kg) were injected and followed by sustaining infusion of saline contaming inulin (5 mg/ml) and urate(0.5mg/ml) at a rate OF 1ml/min, The sustaining infusion was continued to the end of experiment. After an equilibrium period of approximately 40min, three 10.min collection periods were made to determine the control urate clearance, after which a bolus of
PAH (60 mg:k@, probenecid
