Cyclosporine augments reactivity of isolated blood vessels.
Administration of cyclosporine (CS) as an immunosuppressive agent in clinical transplantation is associated with multiple side effects including nephrotoxicity and hypertension. These two effects could be related in that the renal changes may be secondary to alterations in organ blood flow. The present studies investigate the ability of CS to augment contractile responsiveness in blood vessels from normotensive rats. Isometric force generation was measured in isolated tail arteries and portal veins. CS (8.3 X 10(-6)M) potentiated tail artery contractile responses to sympathetic nerve stimulation, exogenous norepinephrine, and increases in extracellular potassium concentration. Portal veins undergo spontaneous contractions which are related to the firing of calcium-driven action potentials in the smooth muscle cells. CS significantly increased the frequency of these spontaneous contractile events. These results suggest that components of CS toxicity may involve a direct action on vascular smooth muscle and/or on vascular adrenergic neurotransmission.
D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats
D003524:Cyclosporins; D009638:Norepinephrine; D010646:Phentolamine