Carbon monoxide–prostaglandin E2 interaction in the hypothalamic circulation

The heme oxygenase (HO)- carbon monoxide pathway was earlier shown to increase hypothalamic blood flow after inhibition of nitric oxide synthesis in rats. We hypothesized that this effect is mediated by prostaglandin E 2 (PGE 2 ). Inhibition of constitutive HO activity decreased cerebral PGE 2 production and simultaneously increased hypothalamic nitric oxide synthase (NOS) activity without changing hypothalamic blood flow. Furthermore, HO blockade induced cyclooxygenase-dependent decrease and NOS-mediated increase of the hypothalamic blood flow after inhibition of NOS and cyclooxygenase, respectively. Therefore, constitutive carbon monoxide release seems to have two indirect effects on the hypothalamic circulation: vasodilation mediated by PGE 2 and vasoconstriction as a result of NOS inhibition.