PMID- 8606521
OWN - NLM
STAT- MEDLINE
DCOM- 19960523
LR  - 20190724
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 26
IP  - 6
DP  - 1995 Dec
TI  - Endothelium-dependent relaxation in the isolated rat kidney: impairment by 
      cyclosporine A.
PG  - 859-68
AB  - The therapeutical use of cyclosporine A (CsA) is hampered by the development of 
      nephrotoxicity characterized by a marked increase in renal vascular resistance 
      (RVR). We investigated vascular functions in kidneys of rats treated with CsA. 
      The ex vivo vascular reactivity of kidneys from control rats and animals treated 
      subacutely with CsA [50 mg/kg/day subcutaneously (s.c.) for 16-21 days] or an 
      olive oil vehicle (1 ml/kg) was analyzed in male Wistar rats. The right kidney 
      was isolated and perfused with Tyrode's or Krebs solution in an open circuit. The 
      effects of acetylcholine (Ach), fenoldopam (FEN), and sodium nitroprusside (SNP) 
      on norepinephrine (NE) preconstricted kidneys were studied. In control kidneys 
      (untreated or vehicle-treated), Ach induced a relaxation (EC50 = 0.56 +/- 0.05 x 
      10(-9)M; Emax = 88.2 +/- 2.1% decrease in the vascular tone restored by NE) which 
      was endothelium-dependent [near-complete abolition after treatment with a 
      detergent, 3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propane-sulfonate (CHAPS) 
      treatment] but only partially inhibited by indomethacin (EC50 = 1.71 +/- 0.39 x 
      10(-9)M, p < 0.05; Emax = 87.1 +/- 4.9%, NS) or indomethacin with 
      NG-nitro-L-arginine methyl ester (L-NAME: EC50 = 1.04 +/- 0.38 x 10(-9)M, NS; 
      Emax = 63.8 +/- 2.5%, p < 0.01). CsA treatment induced a marked decrease in 
      creatinine clearance and natriuresis measured in vivo but had no effect on 
      systolic blood pressure (SBP). In CsA-treated rats, Ach-induced renal relaxation 
      was partially blunted (EC50 = 1.88 +/- 0.34 x 10(-9)M, p < 0.01; Emax = 82.8 +/- 
      4.6, NS), with both a defect in prostaglandin (PG) and nitric oxide (NO)-related 
      responses. CsA treatment had no effect on endothelium-independent relaxations 
      induced by FEN and SNP. These results show that subacute CsA treatment 
      selectively impairs renal endothelium-dependent relaxation related to PGs and NO 
      release.
FAU - Stephan, D
AU  - Stephan D
AD  - Institut de Pharmacologie (ERS 109 CNRS), Faculte de Medecine et Service des 
      Maladies Vasculaires et de l'Hypertension, Hopital Civil, Strasbourg, France.
FAU - Billing, A
AU  - Billing A
FAU - Krieger, J P
AU  - Krieger JP
FAU - Grima, M
AU  - Grima M
FAU - Fabre, M
AU  - Fabre M
FAU - Hofner, M
AU  - Hofner M
FAU - Imbs, J L
AU  - Imbs JL
FAU - Barthelmebs, M
AU  - Barthelmebs M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (Cholic Acids)
RN  - 0 (Immunosuppressive Agents)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - 94ZLA3W45F (Arginine)
RN  - QBP25342AG (3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - Animals
MH  - Arginine/analogs & derivatives/pharmacology
MH  - Body Weight/drug effects
MH  - Cholic Acids/pharmacology
MH  - Cyclosporine/blood/*toxicity
MH  - Endothelium, Vascular/*physiology
MH  - Immunosuppressive Agents/*toxicity
MH  - Indomethacin/pharmacology
MH  - Kidney/*drug effects/pathology/physiology
MH  - Male
MH  - NG-Nitroarginine Methyl Ester
MH  - Perfusion
MH  - Rats
MH  - Rats, Wistar
MH  - Vasodilation/*drug effects
EDAT- 1995/12/01 00:00
MHDA- 1995/12/01 00:01
CRDT- 1995/12/01 00:00
PHST- 1995/12/01 00:00 [pubmed]
PHST- 1995/12/01 00:01 [medline]
PHST- 1995/12/01 00:00 [entrez]
AID - 10.1097/00005344-199512000-00003 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 1995 Dec;26(6):859-68. doi: 
      10.1097/00005344-199512000-00003.