Nitric oxide and prostaglandin pathways interact in the regulation of hypercapnic cerebral vasodilatation.
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.
Heinert
G
G
University Laboratory of Physiology, Parks Road, Oxford, UK.
Nye
P C
PC
Paterson
D J
DJ
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
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D007191:Indazoles; D020030:Nitric Oxide Donors; D011453:Prostaglandins; D009599:Nitroprusside; D009569:Nitric Oxide; D011464:Epoprostenol; C080122:7-nitroindazole