Role of nitric oxide and cAMP in prostaglandin-induced pial arterial vasodilation. 1995

W M Armstead
Department of Anesthesia, University of Pennsylvania, Philadelphia, USA.

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)

UI MeSH Term Description Entries
D007213 Indomethacin A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES. Amuno,Indocid,Indocin,Indomet 140,Indometacin,Indomethacin Hydrochloride,Metindol,Osmosin
D008297 Male Males
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D009712 Nucleotides, Cyclic Cyclic Nucleotide,Cyclic Nucleotides,Nucleotide, Cyclic
D010841 Pia Mater The innermost layer of the three meninges covering the brain and spinal cord. It is the fine vascular membrane that lies under the ARACHNOID and the DURA MATER. Mater, Pia,Maters, Pia,Pia Maters
D011453 Prostaglandins A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. Prostaglandin,Prostanoid,Prostanoids
D011464 Epoprostenol A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY). Prostacyclin,Prostaglandin I2,Epoprostanol,Epoprostenol Sodium,Epoprostenol Sodium Salt, (5Z,9alpha,11alpha,13E,15S)-Isomer,Flolan,Prostaglandin I(2),Veletri
D002536 Cerebral Arteries The arterial blood vessels supplying the CEREBRUM. Arteries, Cerebral,Artery, Cerebral,Cerebral Artery
D005260 Female Females
D006152 Cyclic GMP Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed) Guanosine Cyclic 3',5'-Monophosphate,Guanosine Cyclic 3,5 Monophosphate,Guanosine Cyclic Monophosphate,Guanosine Cyclic-3',5'-Monophosphate,3',5'-Monophosphate, Guanosine Cyclic,Cyclic 3',5'-Monophosphate, Guanosine,Cyclic Monophosphate, Guanosine,Cyclic-3',5'-Monophosphate, Guanosine,GMP, Cyclic,Guanosine Cyclic 3',5' Monophosphate,Monophosphate, Guanosine Cyclic

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