Role of nitric oxide and cAMP in prostaglandin-induced pial arterial vasodilation.
The present study was designed to investigate the role of nitric oxide (NO), guanosine 3',5'-cyclic monophosphate (cGMP), and adenosine 3',5'-cyclic monophosphate (cAMP) in the vasodilator response to prostaglandin (PG)I2 and PGE2 in newborn pigs equipped with a closed cranial window. PGI2 (1-100 ng/ml) produced pial arterial dilation that was blunted by nitro-L-arginine (L-NNA, 10(-6) M), an NO synthase inhibitor (9 +/- 1 vs. 2 +/- 1%, 21 +/- 1 vs. 5 +/- 3% for 1 and 100 ng/ml PGI2 respectively, n = 6; means +/- SE). PGI2-induced vasodilation was associated with increased cortical periarachnoid cerebrospinal fluid (CSF) cGMP, and these changes in cGMP were blocked by L-NNA (386 +/- 8 and 1,054 +/- 30 fmol/ml vs. 266 +/- 6 and 274 +/- 4 fmol/ml for control and PGI2 100 ng/ml before and after L-NNA respectively, n = 6). In contrast, PGI2-associated changes in CSF cAMP were unchanged by L-NNA (1,021 +/- 25 and 2,703 +/- 129 fmol/ml vs. 980 +/- 23 and 2,636 +/- 193 fmol/ml for control, PGI2 100 ng/ml before and after L-NNA, respectively, n = 6). PGE2 elicited similar changes in pial artery diameter and cyclic nucleotides; vasodilation and changes in CSF cGMP also being similarly inhibited by L-NNA. After L-NNA, topical administration of the NO donor sodium nitroprusside (SNP, 10(-9) M) increased pial artery diameter up to the resting level before L-NNA and partially restored the vasodilation elicited by PGI2 and PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)
Armstead
W M
WM
Department of Anesthesia, University of Pennsylvania, Philadelphia, USA.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects*; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000134:cerebrospinal fluid; D015232:Dinoprostone / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D009712:Nucleotides, Cyclic / Q000134:cerebrospinal fluid; D010841:Pia Mater / Q000098:blood supply*; D011453:Prostaglandins / Q000494:pharmacology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D009712:Nucleotides, Cyclic; D011453:Prostaglandins; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D011464:Epoprostenol; D000242:Cyclic AMP; D006152:Cyclic GMP; D015232:Dinoprostone; D007213:Indomethacin