Interleukin 1 inhibits contraction of vascular smooth muscle.
Interleukin 1 has been implicated as a mediator of both systemic and local responses to infection and injury. Since systemic and local vasodilatation are hallmarks of sepsis and infection, we studied the direct effect of IL-1 on vascular contractility. We report here that human recombinant IL-1-beta potently inhibits the response of rat thoracic aorta to vasoconstrictor agents. Exposure of isolated rat aortic rings to IL-1 (20 ng/ml) for 1 h did not affect phenylephrine-induced contractions during the exposure period. However, when rings were retested 150-200 min after initiation of IL-1 exposure, contractions were markedly decreased. The cytokine had a similar effect in rings from which the endothelium was removed. Contractions caused by potassium depolarization also were depressed, indicating the effect of IL-1 is not specific to the alpha-adrenoceptor agonist. The inhibitory effect of IL-1 was concentration-dependent (0.2 to 20 ng/ml), and eliminated by pretreatment with cycloheximide (20 micrograms/ml). Indomethacin (10(-5) M) did not prevent the inhibition caused by IL-1. These studies identify IL-1 as a potent inhibitor of vascular contraction, via an endothelium-independent mechanism. Studies with inhibitors suggest that the action of IL-1 is independent of prostanoid synthesis, and may involve synthesis of protein.
Evans Memorial Department of Clinical Research, University Hospital at Boston University Medical Center, Massachusetts 02118.
D
D
Beasley
R A
RA
Cohen
N G
NG
Levinsky
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D007375:Interleukin-1; D011994:Recombinant Proteins; D010656:Phenylephrine; D003513:Cycloheximide; D007213:Indomethacin