title: Nitric oxide and prostaglandin pathways interact in the regulation of hypercapnic cerebral vasodilatation.
abstract: To test whether nitric oxide and prostaglandin pathways interact in hypercapnic cerebral vasodilatation, cerebral blood flow (CBF) was measured in enflurane anaesthetized Sprague-Dawley rats using the hydrogen clearance method. Isometric tension was measured in rat middle cerebral arteries in vitro. The neuronal NO synthase inhibitor 7-nitroindazole (7-NI 60 mg kg-1 i.p.) reduced the hypercapnic CBF response by 62 +/- 7% (but not the hypoxic response) and indomethacin (IMC 6 mg kg-1 i.v.) reduced the hypercapnic CBF response by 60 +/- 5%. Combined application caused only an 80 +/- 1% reduction. The attenuation of hypercapnic CBF by IMC was diminished by 7-NI and similarly 7-NI had less effect in the presence of IMC. Spermine-NO (50 microM 0.5 microL min-1 intracortically) increased eucapnic and hypercapnic CBF in the presence of IMC. In isolated middle cerebral arteries, combined application of sodium nitroprusside (SNP 3 nM) and prostacyclin (30 nM) had a synergistic vasodilatory effect. Milrinone (PDE-III inhibitor) also potentiated prostacyclin-mediated vasodilatation. Our results suggest that the NO- and IMC-sensitive pathways involved in the hypercapnic response are distinct, however, both may interact synergistically. A similar synergism was observed between the effects of SNP and prostacyclin.
authors.affiliation: University Laboratory of Physiology, Parks Road, Oxford, UK.
authors.forename: G
authors.initials: G
authors.lastname: Heinert
authors.forename: P C
authors.initials: PC
authors.lastname: Nye
authors.forename: D J
authors.initials: DJ
authors.lastname: Paterson
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002560:Cerebrovascular Circulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D006935:Hypercapnia / Q000378:metabolism* / Q000503:physiopathology*; D007191:Indazoles / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014664:Vasodilation
chemical_list: D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D007191:Indazoles; D020030:Nitric Oxide Donors; D011453:Prostaglandins; D009599:Nitroprusside; D009569:Nitric Oxide; D011464:Epoprostenol; C080122:7-nitroindazole