Mechanism of hind limb vasoconstriction due to cyclosporin A in the dog.
Cyclosporin A (CSA) causes an acute vasoconstriction of hind limb arterial vessels. To determine the mechanism of action of CSA on the peripheral arterial bed, studies were performed on the isolated femoral artery perfused at constant flow in 61 dogs. Changes in femoral perfusion pressure reflected variations in vascular resistance. Pure powder CSA was dissolved in autologous blood and injected at doses of 1, 5, 10, and 20 mg. Infusions of 1 and 5 mg CSA caused nonsignificant mean increases of 4 +/- 2 mm Hg (95% confidence interval [CI], 0-8; p > 0.05) and 10 +/- 4 mm Hg (95% CI, 0-21; p > 0.05) in femoral perfusion pressure, with CSA blood levels in the femoral vein averaging 40 +/- 16 and 126 +/- 50 nmol/l, respectively, at the end of the injections. Infusions of 10 and 20 mg CSA caused significant increases in femoral perfusion pressure averaging of 8 +/- 3 mm Hg (95% CI, 1-14; p < 0.05) and 20 +/- 4 mm Hg (95% CI, 11-29; p < 0.05) in femoral perfusion pressure. CSA blood levels at the end of injections averaged 271 +/- 99 and 431 +/- 146 nmol/l, respectively, in the femoral vein. Blockade of alpha-adrenergic receptors with phentolamine and surgical lumbar sympathectomy decreased significantly the CSA vasoconstrictive effect in peripheral arterial vessels, with increases in perfusion pressure averaging 29 +/- 5 mm Hg before and 14 +/- 3 mm Hg after phentolamine (p < 0.05) and 30 +/- 2 mm Hg before and 8 +/- 2 mm Hg after sympathectomy (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Surgery, Montreal Heart Institute, Quebec, Canada.
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D004285:Dogs / Q000097:blood; D006614:Hindlimb / Q000098:blood supply* / Q000294:innervation; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D012018:Reflex / Q000187:drug effects; D013562:Sympathectomy; D014439:Tyramine / Q000494:pharmacology; D014661:Vasoconstriction
D000317:Adrenergic alpha-Antagonists; D016572:Cyclosporine; D005996:Nitroglycerin; D009638:Norepinephrine; D014439:Tyramine