Contribution of the Heme Oxygenase Pathway to the Maintenance of the Hypothalamic Blood Flow During Diminished Nitric Oxide Synthesis

• Published in: Journal of cerebral blood flow and metabolism Vol. 23; no. 6; pp. 653 - 657
• Main Authors: HORVATH, Béla, HRABAK, Andras, KALDI, Krisztina, SANDOR, Péter, BENYO, Zoltan
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.06.2003; Lippincott Williams & Wilkins; Sage Publications Ltd
• Subjects: Acid-Base Equilibrium - physiology; Animals; Biological and medical sciences; Carbon Monoxide - metabolism; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Cerebrovascular Circulation - drug effects; Cerebrovascular Circulation - physiology; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Heme Oxygenase (Decyclizing) - metabolism; Heme Oxygenase-1; Hypothalamus - blood supply; Hypothalamus - enzymology; Male; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase - metabolism; Rats; Rats, Wistar; Vasodilation - drug effects; Vasodilation - physiology; Vertebrates: nervous system and sense organs; Endothelial dysfunction; Nitric oxide synthase; Hypothalamus; Heme oxygenase; Regional blood flow; Rat; Enzyme; Rodentia; Heme oxygenase (decyclizing); Experimental study; Nitric-oxide synthase; Vertebrata; Mammalia; Animal; Heme oxygenase-Nitric oxide synthase-Hypothalamus-Endothelial dysfunction; Physiology; Hemodynamics; Oxidoreductases; Brain (vertebrata)
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1097/01.WCB.0000071890.63724.C9

The cerebrovascular effects of the heme oxygenase–carbon monoxide pathway were studied in the rat hypothalamus. Intraperitoneal administration of the heme oxygenase inhibitor zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG, 45 μmol/kg) had no significant effect on the resting cerebral blood flow, but increased hypothalamic nitric oxide synthase activity by 67% without changing the CSF cyclic GMP concentration. After pharmacologic inhibition of nitric oxide synthase, the diminished cerebral blood flow was further reduced by 22% after administration of ZnDPBG, and the effect showed direct correlation with the baseline perfusion level. Therefore, endogenous carbon monoxide may significantly contribute to the cerebral vasoregulation under resting conditions and in pathophysiologic states associated with diminished nitric oxide synthesis.