Cardiovascular and renal sympathetic activation by blood-borne TNF-alpha in rat: the role of central prostaglandins.
In pathophysiological conditions, increased blood-borne TNF-alpha induces a broad range of biological effects, including activation of the hypothalamic-pituitary-adrenal axis and sympathetic drive. In urethane-anesthetized adult Sprague-Dawley rats, we examined the mechanisms by which blood-borne TNF-alpha activates neurons in paraventricular nucleus (PVN) of hypothalamus and rostral ventrolateral medulla (RVLM), two critical brain regions regulating sympathetic drive in normal and pathophysiological conditions. TNF-alpha (0.5 microg/kg), administered intravenously or into ipsilateral carotid artery (ICA), activated PVN and RLVM neurons and increased sympathetic nerve activity, arterial pressure, and heart rate. Responses to intravenous TNF-alpha were not affected by vagotomy but were reduced by mid-collicular decerebration. Responses to ICA TNF-alpha were substantially reduced by injection of the cyclooxygenase inhibitor ketorolac (150 microg) into lateral ventricle. Injection of PGE(2) (50 ng) into lateral ventricle or directly into PVN increased PVN or RVLM activity, respectively, and sympathetic drive, with shorter onset latency than blood-borne TNF-alpha. These findings suggest that blood-borne cytokines stimulate cardiovascular and renal sympathetic responses via a prostaglandin-dependent mechanism operating at the hypothalamic level.
Zhang
Zhi-Hua
ZH
Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine and Medical Service, Iowa City, Iowa 52242, USA.
Wei
Shun-Guang
SG
Francis
Joseph
J
Felder
Robert B
RB
D000818:Animals; D001794:Blood Pressure; D002319:Cardiovascular System / Q000187:drug effects* / Q000294:innervation*; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate; D020910:Ketorolac / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000294:innervation*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D014628:Vagotomy
D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone; D020910:Ketorolac