Functional analysis of vascular dysfunction in cyclosporin treated rats.
OBJECTIVE
The aim was to analyse vascular damage after chronic cyclosporin treatment (20 mg.kg-1 during 10 d) in rats.


METHODS
The reactivity to different vasoactive agents was studied on thoracic aortic rings from control rats, and from rats subjected to renal ablation or cyclosporin treatment.


RESULTS
After cyclosporin treatment the endothelium dependent vasodilator responses to acetylcholine and to the endothelium independent NO donors were suppressed. These defects were restored after a 7 d recovery period. The contractile response after inhibition of basal endothelial NO synthesis was unaffected. Further analysis of the blunted vasodilatations not only points to impairments of cGMP mediated mechanisms but shows that other pathways are possibly involved as well. Renal insufficiency induced by renal mass reduction did not influence the aortic reactivity.


CONCLUSIONS
Cyclosporin induced vasculotoxicity is a reversible phenomenon, and is not due to renal dysfunction as such. It seems to provoke a defect in the vasodilator mechanisms at the level of the vascular smooth muscle cells and most likely no impairment of endothelial nitric oxide production.
University Hospital, Gent, Belgium.
M
M
Verbeke
J
J
Van de Voorde
L
L
de Ridder
N
N
Lameire
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis; D003524:Cyclosporins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D009392:Nephrectomy; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D003524:Cyclosporins; D009569:Nitric Oxide; D001120:Arginine; D005996:Nitroglycerin; D006152:Cyclic GMP; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester