[On the mechanism underlying spasmogenic actions of oxy-hemoglobin on the cerebral artery, analyzed from the inhibitory effects of nicardipine, procaine and indomethacin].
The present study was to analyze the basic mechanism underlying spasmogenic actions of Oxy-hemoglobin (Oxy-Hb) on the bovine cerebral arteries. Using helical strips of the middle cerebral arteries (M2), the changes in muscular tension during an isometric contraction induced by either Oxy-Hb, hydrogen peroxide (H2O2), high potassium-ion-Tyrode (30 mM K+), prostaglandin F2 alpha (PGF2 alpha), or carbocyclic thromboxane A2 (cTXA2) were recorded on the polygraph. Blocking effects of nicardipine, procaine indomethacin were compared on the contractions produced by each reagent described above. The results obtained are summarized as follows. 1) H2O2 dissolved in different concentrations produced arterial contractions similar to those by equimolar Oxy-Hb, showing similar dose-response curves. In contrast, equimolar met-hemoglobin (Met-Hb) always produced much weaker contractions. When the equimolar H2O2 was applied during an Oxy-Hb-induced contraction, the response to H2O2 was completely occluded. When H2O2 was applied during a Met-Hb-induced contraction, the response to H2O2 was not occluded and always additive to the response to Met-Hb. Indomethacin blocked both responses to Oxy-Hb and H2O2, showing similar dose dependence. 2) The above results suggested that Oxy-Hb induced contraction consisted of two components; a strong contraction by active oxygen within Hb molecule, and a weak contraction by Hb molecule itself. The former may be mediated by some PG's which are produced inside the muscle cells as the results of arachidonic acid release and subsequent cyclooxygenase activation.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Neurosurgery, Iwate Medical University, School of Medicine, Morioka, Japan.
D000818:Animals; D002417:Cattle; D002539:Cerebral Arterial Diseases / Q000139:chemically induced* / Q000517:prevention & control; D066298:In Vitro Techniques; D007213:Indomethacin / Q000627:therapeutic use*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009529:Nicardipine / Q000627:therapeutic use*; D010108:Oxyhemoglobins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011343:Procaine / Q000627:therapeutic use*; D013035:Spasm / Q000139:chemically induced* / Q000517:prevention & control
D010108:Oxyhemoglobins; D011343:Procaine; D009529:Nicardipine; D007213:Indomethacin