Cardiorespiratory responses to interleukin-1beta in adult rats: role of nitric oxide, eicosanoids and glucocorticoids.
Interleukin-1beta (IL-1beta) receptors are abundantly expressed in brain stem regions involved in respiratory control. We hypothesized that systemic administration of IL-1beta would increase ventilation (V(E )), and that nitric oxide, eicosanoids, and glucocorticoid receptors would modulate IL-1beta-induced cardioventilatory responses. Intravenous injections of three doses (37.5 ng kg(-1), 75 ng kg(-1 ) and 150 ng kg(-1)) of IL-1b induced monophasic increases in (V(E)), heart rate (HR), and blood pressure (BP) which had a distinctly different onset and duration of action compared to IL-1beta-induced body temperature elevations. Pre-treatment with the nitric oxide inhibitor L-NAME was associated with decreased peak V(E) responses, without affecting the latency and duration of IL-1beta. L-NAME also enhanced HR responses while pressor responses were attenuated. Eicosanoid inhibition with indomethacin resulted in markedly attenuated V responses. However, cardiovascular responses to IL-1beta were not modified by indomethacin. In contrast, pre-treatment with dexamethasone, was not associated with any changes in the IL-1beta-induced V(E), HR, or BP responses. We conclude that IL-1beta increases of V(E) are dose-dependent and are not time-locked with the pyrexic response suggesting the possibility that distinct neural pathways may underlie these responses. In addition, nitric oxide and eicosanoid-dependent mechanisms modulate IL-1beta ventilatory effects.
Graff
G R
GR
Department of Pediatrics and Physiology, Constance S. Kaufman Pediatric Pulmonary Research Laboratory, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Gozal
D
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015777:Eicosanoids / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced; D005938:Glucocorticoids / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000502:physiology*; D012119:Respiration / Q000187:drug effects*
D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D007375:Interleukin-1; D011965:Receptors, Glucocorticoid; D009569:Nitric Oxide; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin