Compensatory role of NO in cerebral circulation of piglets chronically treated with indomethacin.
We hypothesize that inhibitory effects exist between prostanoids and nitric oxide (NO) in their contributions to cerebral circulation. Piglets (1-4 days old) were divided into three chronically treated (6-8 days) groups: control piglets, piglets treated with indomethacin (75 mg/day), and piglets treated with N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 mg x kg(-1) x day(-1)). Pial arterioles dilated in response to hypercapnia similarly among the three groups (41 +/- 4, 40 +/- 6, and 45 +/- 11%). Cerebrospinal fluid cAMP increased in control piglets, while cGMP increased in indomethacin-treated piglets. L-NAME, but not 7-nitroindazole, inhibited the response to hypercapnia only in indomethacin-treated piglets (40 +/- 6 vs. 17 +/- 5%). Topical sodium nitroprusside or iloprost restored dilation in response to hypercapnia. Similar results were obtained when the dilator was bradykinin. Pial arterioles of control and L-NAME-treated piglets constricted in response to ACh (-24 +/- 3%). However, those of indomethacin-treated piglets dilated in response to ACh (15 +/- 2%). This dilation was inhibited by L-NAME. NO synthase activity, but not endothelial NO synthase expression, increased after chronic indomethacin treatment. These data suggest that chronic inhibition of cyclooxygenase can increase the contribution of NO to cerebrovascular circulatory control in piglets.
Zhang
Yifan
Y
Laboratory for Research in Neonatal Physiology, Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Leffler
C W
CW
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001920:Bradykinin / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000134:cerebrospinal fluid; D006152:Cyclic GMP / Q000134:cerebrospinal fluid; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006935:Hypercapnia / Q000378:metabolism; D007191:Indazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology*; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000032:analysis; D052250:Nitric Oxide Synthase Type III; D010841:Pia Mater / Q000098:blood supply; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology
D002317:Cardiovascular Agents; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007191:Indazoles; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP; D000109:Acetylcholine; D001920:Bradykinin; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin