title: Effects of tumor necrosis factor and interleukin-1 on the constriction induced by angiotensin II in rat aorta.
abstract: To better understand the different steps in the changes occurring in vascular reactivity during sepsis, we studied the effects of a short exposure to tumor necrosis factor (TNF) and interleukin-1 (IL-1) on the contraction in response to angiotensin II (ANG II). The contraction elicited by ANG II was studied by using standard isometric tension techniques in aortic rings exposed for 1 h to 25 ng/ml TNF or to 5 or 20 ng/ml IL-1. This contraction was not significantly changed by TNF but was 109 +/- 23 and 190 +/- 38% greater than in control rings after 5 and 20 ng/ml IL-1, respectively. Because the contraction induced by ANG II is modulated by the simultaneous release of prostaglandins, we tested the hypothesis that IL-1 interferes with this modulation. We found that the IL-1-induced increase in contraction in response to ANG II was completely inhibited by 10(-5) M of the cyclooxygenase inhibitor indomethacin and also by 10(-5) M of the prostaglandin H2/thromboxane A2-receptor antagonist SQ-29548. Note, however, that in rings exposed to IL-1 the contraction in response to the thromboxane A2-receptor agonist U-46619 was not significantly different from the contraction in unexposed rings. Furthermore, no loss was observed in either the vasodilator response to 10(-9)-10(-4) M of the endothelium-dependent-receptor agonist acetylcholine or in the receptor-independent contraction induced by 60 mM K+. We conclude that short exposure to IL-1, but not to TNF, produces a specific increase in the vasoconstrictor response to ANG II via mechanisms mediated by prostaglandin H2/thromboxane A2. This increase might result from an IL-1-induced shift in favor of constrictor prostanoids in the balance of the dilator/constrictor prostanoids, the release of which is associated with stimulation by ANG II.
authors.affiliation: Laboratoire d'Etude de la Microcirculation, Hopital Fernand Widal, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Vicaut
authors.forename: C
authors.initials: C
authors.lastname: Rasetti
authors.forename: N
authors.initials: N
authors.lastname: Baudry
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D000109:Acetylcholine