Nitric oxide and prostaglandin pathways interact in the regulation of hypercapnic cerebral vasodilatation

To test whether nitric oxide and prostaglandin pathways interact in hyperca pnic cerebral vasodilatation, cerebral blood flow (CBF) was measured in enf lurane anaesthetized Sprague-Dawley rats using the hydrogen clearance metho d. 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 re sponse) and indomethacin (IMC 6 mg kg(-1) i.v.) reduced the hypercapnic CBF response by 60 +/- 5%. Combined application caused only an 80 +/- 1% reduc tion. 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 mu M 0.5 mu L min(-1) intracortically) increased eucapnic and hypercapnic CBF i n the presence of IMC. In isolated middle cerebral arteries, combined appli cation of sodium nitroprusside (SNP 3 nM) and prostacyclin (30 nM) had a sy nergistic vasodilatory effect. Milrinone (PDE-III inhibitor) also potentiat ed prostacyclin-mediated vasodilatation. Our results suggest that the NO- a nd IMC-sensitive pathways involved in the hypercapnic response are distinct , however, both may interact synergistically. A similar synergism was obser ved between the effects of SNP and prostacyclin.