Role of nitric oxide and cAMP in beta-adrenoceptor-induced pial artery 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 beta-adrenoceptor agonists in newborn pigs equipped with a closed cranial window. Dobutamine (10(-8) and 10(-6) M), a beta 1-agonist, produced pial artery dilation that was blunted by NG-nitro-L-arginine (L-NNA; 10(-6) M), a NO synthase inhibitor (12 +/- 1 vs. 0 +/- 2% and 24 +/- 3 vs. 4 +/- 1% for 10(-8) and 10(-6) M dobutamine, respectively). Dobutamine-induced vasodilation was associated with increased cortical periarachnoid cerebrospinal fluid (CSF) cGMP, and these changes in CSF cGMP were blocked by L-NNA (391 +/- 10 and 675 +/- 36 fmol/ml vs. 307 +/- 3 and 346 +/- 37 fmol/ml for control and 10(-6) M dobutamine before and after L-NNA, respectively). In contrast, dobutamine-associated changes in CSF cAMP were unchanged by L-NNA (1,108 +/- 56 and 2,623 +/- 139 fmol/ml vs. 1,059 +/- 24 and 2,500 +/- 61 fmol/ml for control and 10(-6) M dobutamine before and after L-NNA, respectively). Salbutamol, a beta 2-agonist, and isoproterenol, a nonselective beta-agonist, elicited similar changes in pial diameter and cyclic nucleotides; vasodilation and changes in CSF cGMP also were similarly inhibited by L-NNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Rebich
S
S
Department of Anesthesia, University of Pennsylvania, Philadelphia.
Devine
J O
JO
Armstead
W M
WM
D000420:Albuterol / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology; D004280:Dobutamine / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply* / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D009599:Nitroprusside; D005576:Colforsin; D019335:Nitroarginine; D009569:Nitric Oxide; D004280:Dobutamine; D001120:Arginine; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP; D007545:Isoproterenol; D000420:Albuterol