Inhibition of brain nitric oxide synthesis enhances and prolongs the hypertensive effect of centrally administered interleukin-1beta in rats.
The present study was designed to find out whether brain nitric oxide (NO) influences hemodynamic response to intracerebroventricular (ICV) infusion of interleukin-1 beta (IL-1beta). Mean arterial blood pressure (MAP) and heart rate (HR) were recorded in seven series of experiments performed on conscious Sprague-Dawley rats receiving during 60 min ICV infusion of: 0.9% NaCl (5 microl/h; series 1), IL-1beta (100 ng/h; series 2), NO synthase inhibitor (L-NAME, 1mg/h; series 3), IL-1beta together with L-NAME (series 4), IL-1beta together with inactive isomer of NO synthase inhibitor (D-NAME, 1mg/h; series 5), NO donor (SNAP, 40 microg/h; series 6) and IL-1beta together with SNAP (series 7). ICV infusion of saline did not influence MAP while administration of IL-1beta as well as IL-1beta together with D-NAME elicited a significant, though transient, increase in MAP. In series 4, combined infusion of IL-1beta and L-NAME exerted an increase in MAP, which persisted until the end of the experiment and was significantly higher than in series 2 and 5. In series 7, infusion of SNAP together with IL-1beta abolished the pressor effect of IL-1beta. HR was not significantly altered in any of the experimental series. These results demonstrate that inhibition of NO synthesis in the brain enhances and prolongs the pressor response to IL-1beta, whereas concomitant administration of NO donor abolishes the hemodynamic effect of IL-1beta. Therefore, we conclude that NO generated in the brain is involved in buffering the pressor response to IL-1beta.
Ufnal
Marcin
M
Department of Experimental and Clinical Physiology, Medical University of Warsaw, Krakowskie Przedmieście 26/28, 00-927 Warsaw, Poland. marcinufnal@poczta.onet.pl
Dudek
Magdalena
M
Szczepańska-Sadowska
Ewa
E
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002552:Cerebral Ventricles; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D007375:Interleukin-1; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester