Difference between aortic and renal vascular reactivity in cyclosporin A treated rats and the effect of cicletanine.
4 Groups of 2 month-old male Wistar rats were treated with a) cyclosporin A (CyA) 30 mg/kg/day alone, b) CyA plus cicletanine (Cic) 60 mg/kg/day, c) vehicle (vegetable oil) 1 ml/100 g rat/day and d) no treatment for 8 weeks. The reactivity of isolated papillary muscle to isoprenaline and Ca2+ was not altered in any of the treated groups. Endothelium-dependent relaxation induced by acetylcholine was inhibited in aorta ring segments from CyA-treated rats as compared to that of control and CyA + Cic-treated rats. The relaxation induced by acetylcholine in rat aortas was similar in all groups in the presence of 10 microM indomethacin. Noradrenaline sensitivity of aortic segments was not affected by any treatments applied. The Ca(2+)-concentration response curves of aorta segments from CyA-treated and CyA + Cic-treated rats were shifted to the right as compared to control rats. In interlobar renal arteries the endothelium-dependent relaxation induced by acetylcholine was not affected by any form of treatment. In renal arteries 10 microM indomethacin increased the maximal relaxation induced by acetylcholine about 50%. In these vessels noradrenaline sensitivity in CyA and CyA + Cic treated rats was higher than in controls. Cocaine, 3 microM, shifted the noradrenaline concentration response curve to the left about 0.4 log units in all renal vessel groups, thus renal vascular smooth muscle sensitivity to noradrenaline was significantly greater in vessels from rats receiving CyA than in vessels from control rats. Administration of CyA induced only slight renal morphological changes. Cic was without effect on CyA induced morphological abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
Mikkelsen
E O
EO
Department of Pharmacology, Aarhus University, Denmark.
Poulsen
S H
SH
Nyborg
N C
NC
Korsgaard
N
N
Sehested
J
J
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000033:anatomy & histology / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D011725:Pyridines; D051381:Rats; D011919:Rats, Inbred Strains; D012077:Renal Artery / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D004232:Diuretics; D011725:Pyridines; D014665:Vasodilator Agents; D016572:Cyclosporine; C038068:cicletanine