Contributions of prostacyclin and nitric oxide to carbon monoxide-induced cerebrovascular dilation in piglets.
Carbon monoxide (CO) is an endogenous dilator in the newborn cerebral microcirculation. Other dilators include prostanoids and nitric oxide (NO), and interactions among the systems are likely. Experiments on anesthetized piglets with cranial windows address the hypothesis that CO-induced dilation of pial arterioles involves interaction with the prostanoid and NO systems. Topical application of CO or the heme oxygenase substrate heme-L-lysinate (HLL) produced dilation. Indomethacin, N(omega)-nitro-L-arginine (L-NNA), and either iberiotoxin or tetraethylammonium chloride (TEA) were used to inhibit prostanoids, NO, and Ca(2+)-activated K(+) (K(Ca)) channels, respectively. Indomethacin, L-NNA, iberiotoxin, or TEA blocked cerebral vasodilation to CO and HLL. Vasodilations to both CO and HLL were returned to indomethacin-treated piglets by topical application of iloprost. Vasodilations to both CO and HLL were returned to L-NNA-treated piglets by sodium nitroprusside but not iloprost. In iberiotoxin- or TEA-treated piglets, dilations to CO and HLL could not be restored by either iloprost or sodium nitroprusside. The dilator actions of CO involve prostacyclin and NO as permissive enablers. The permissive actions of prostacyclin and NO may alter the K(Ca) channel response to CO because neither iloprost nor sodium nitroprusside could restore dilation to CO when these channels were blocked.
Leffler
C W
CW
Laboratory for Research in Neonatal Physiology, Departments of Physiology and Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. cleffler@physio1.utmem.edu
Nasjletti
A
A
Johnson
R A
RA
Fedinec
A L
AL
D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D002248:Carbon Monoxide / Q000494:pharmacology*; D006418:Heme / Q000031:analogs & derivatives / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D012604:Scorpion Venoms / Q000494:pharmacology; D013552:Swine; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D010455:Peptides; D015221:Potassium Channels; D012604:Scorpion Venoms; D014665:Vasodilator Agents; C106087:heme lysinate; D019335:Nitroarginine; D009569:Nitric Oxide; D006418:Heme; D019789:Tetraethylammonium; C064719:iberiotoxin; D002248:Carbon Monoxide; D008239:Lysine; D007213:Indomethacin