Contribution of the heme oxygenase pathway to the maintenance of the hypothalamic blood flow during diminished nitric oxide synthesis.
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 micro mol/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.
Horváth
Béla
B
Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary.
Hrabák
András
A
Káldi
Krisztina
K
Sándor
Péter
P
Benyó
Zoltán
Z
D000136:Acid-Base Equilibrium / Q000502:physiology; D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D007031:Hypothalamus / Q000098:blood supply* / Q000201:enzymology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D019331:NG-Nitroarginine Methyl Ester