Acute effects of rapamycin on glomerular dynamics: a micropuncture study in the rat.
The acute effects of cyclosporin (CsA, 20 mg(kg i.v.) and rapamycin (RAPA, 5 mg(kg i.v.) on glomerular dynamics were separately investigated by renal micropuncture in two groups of intact rats (group CsA and RAPA, respectively) and compared with vehicle-treated rats, used as controls (group CON). Left kidney glomerular filtration rate (GFR) was decreased by CSA (-35% vs. CON, P<0.05), but was not affected by RAPA (-14% vs. CON, NS), whereas the single-nephron GFR (SNGFR) was significantly decreased in both groups (-40% in CsA, P<0.01 and -26% in RAPA, P<0.05 vs. CON). In both groups glomerular plasma flow (GPF) was significantly reduced vs. CON (CsA: -48%, and RAPA: -25%) due to the increase in both afferent (Ra) and efferent (Re) glomerular resistances: group CSA showed a prevalent rise in Re (+98% vs. CON, P<0.001) than in Ra (+66%, P<0.001); in group RAPA the increment was modest and similar in Ra and Re (+33 and +32%, respectively, NS versus CON). A further group of rats was studied in which L-Arginine (ARG), the precursor of nitric oxide (NO), was administered (2.5 mg/Kg/min iv) with RAPA (group ARG). ARG limited the rise in Ra and Re, thereby preserving GPF; nevertheless, SNGFR remained low (-26% vs. CON, P<0.05) due to the decrease in the effective filtration pressure (-26% vs. CON). These data demonstrate that: (1) CsA is nephrotoxic at immunosuppressive doses; (2) RAPA, even at huge doses, has marginal effects on renal and glomerular dynamics; (3) the ARG-NO pathway is only partially involved in the vasoconstriction of superficial nephrons after RAPA administration.
Sabbatini
M
M
Department of Nephrology, University Federico II, Naples, Italy.
Sansone
G
G
Uccello
F
F
De Nicola
L
L
Nappi
F
F
Andreucci
V E
VE
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007328:Insulin / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D011677:Punctures; D051381:Rats; D020123:Sirolimus / Q000633:toxicity*
D007166:Immunosuppressive Agents; D007328:Insulin; D009569:Nitric Oxide; D016572:Cyclosporine; D001120:Arginine; D020123:Sirolimus