[Selective augmenting effect of oxy-Hb on the contractions of cerebral arteries elicited by various vasoactive...

Serotonin (5-HT), histamine (HA), angiotensin II (ATII), prostaglandin F2 alpha (PGF2 alpha) and thromboxane A2 (TxA2) are known as vasoactive substances, each producing a characteristic contraction of cerebral arteries. These contractions are considered to be mediated by their specific receptors. Recent studies suggest that the activations of these receptors primarily stimulate the phospholipase C and/or phospholipase A2 localized within the same membrane. Stimulation of these enzymes consequently induces production of the second or third messengers such as inositol triphosphate (IP3), diacylglyceride (DAG), arachidonic acid (AA), and ultimately various prostaglandins. The present study is to examine how oxyhemoglobin (Oxy-Hb), another vasoactive substance, can modify these receptor-mediated contractions, and to compare the effects on high K+-, caffeine-and 1-oleoyl-2-acetyl-rac-glycerol (OAG)-induced contractions which are not mediated by the receptors on the cytoplasmic membrane. Helical strips of the bovine middle cerebral arteries (M2) were mainly used in this experiment, and the changes in muscular tensions during isometric contractions were recorded on the polygraph. 5-HT, HA, ATII, PGF2 alpha and cTxA2 (carbocyclic thromboxane A2) were used for each receptor activation. Indomethacin (IDM), a cyclooxygenase inhibitor and 2-nitro-4-carboxyphenyl-n, n-diphenyl-carbamate (NCDC), a phospholipase C inhibitor were used to analyze a possible acting site of Oxy-Hb in modifying these reseptor-mediated enzyme reactions. The results obtained are summarized as follows. (1) All contractions induced by either 5-HT, PGF2 alpha, cTxA2, HA or ATII (concentrations less than 10(-6) M) were markedly augmented as much as 4-8 times the normal, when they were examined in the presence of 10(-5)M Oxy-Hb.(ABSTRACT TRUNCATED AT 250 WORDS)