Fever induced by platelet-derived growth factor, in contrast to fever induced by lipopolysaccharide, depends only on nitric oxide, but not on carbon monoxide pathway

• Published in: European journal of pharmacology Vol. 467; no. 1; pp. 133 - 140
• Main Authors: Almeida, Maria Camila, Pelá, Irene Rosemir, Branco, Luiz Guilherme S
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25-04-2003; Elsevier
• Subjects: Animals; Becaplermin; Biological and medical sciences; Body Temperature - drug effects; Body Temperature - physiology; Carbon Monoxide - physiology; Citrulline - analogs & derivatives; Citrulline - pharmacology; Deuteroporphyrins - pharmacology; Enzyme Inhibitors - pharmacology; Fever; Fever - chemically induced; Fever - metabolism; Heme oxygenase; Heme Oxygenase (Decyclizing) - antagonists & inhibitors; Heme Oxygenase (Decyclizing) - physiology; Isoenzymes - antagonists & inhibitors; Lipopolysaccharides; Male; Medical sciences; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide (NO) synthase; Nitric Oxide - physiology; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - physiology; Nitric Oxide Synthase Type II; PDGF (platelet-derived growth factor); Platelet-Derived Growth Factor - antagonists & inhibitors; Platelet-Derived Growth Factor - physiology; Proto-Oncogene Proteins c-sis; Rats; Rats, Wistar; Thiourea - analogs & derivatives; Thiourea - pharmacology; PDGF (platelet-derived growth factor); Nitric oxide (NO) synthase; Fever; Heme oxygenase
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(03)01636-4

Platelet-derived growth factor (PDGF) is a multifunctional protein which is known to induce a febrile response when injected intracerebroventricularly. The gaseous neurotransmitters, nitric oxide (NO) and carbon monoxide (CO), are both known to exert thermoregulatory effects and to participate in lipopolysaccharide-induced fever. In this study, we investigated the role of NO and CO in the febrile response to PDGF-BB in rats. Intracerebroventricular (i.c.v.) injection of PDGF-BB produced a dose-dependent increase in body temperature. This increase in body temperature induced by PDGF-BB was exacerbated by
N
G-nitro-
l-arginine methyl ester (
l-NAME—a nonselective NO synthase inhibitor) and
S-methyl-
l-thiocitrulline treatment [SMTC—a neuronal NOS (nNOS) selective inhibitor], but not by aminoguanidine treatment [an inducible NOS (iNOS) selective inhibitor]. Zinc deuteroporphyrin 2,4-bis glycol treatment (ZnDPBG—a nonselective heme oxygenase (HO) blocker) did not affect PDGF-BB fever. Our data indicate that the NO but not the CO pathway participates in PDGF-BB fever. Furthermore, our data show that nNOS is the NOS isoform responsible for NO synthesis in this response.