Impaired cerebral vasodilator responses to NO and PDE V inhibition after subarachnoid hemorrhage.
Subarachnoid hemorrhage (SAH) is associated with impaired nitric oxide (NO)-mediated cerebral vasodilatation. We tested the hypothesis that SAH causes alterations in the production of, hydrolysis of, or responsiveness to cGMP in the rat basilar artery in vivo. Rats were injected with saline or autologous blood into the cisterna magna. Two days later, effects of vasoactive drugs on basilar artery diameter were examined using a cranial window preparation. Vasodilator responses to ACh, sodium nitroprusside (SNP), and low concentrations (</=10(-5) M) of zaprinast, an inhibitor of phosphodiesterase V (PDE V), were impaired in SAH rats (P < 0.05). In contrast, vasodilator responses to adenosine and 8-BrcGMP were similar in control and SAH rats. Vasoconstrictor responses to 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase, were unaffected by SAH. In the presence of zaprinast (10(-5)-10(-4) M), responses to ACh and SNP were equivalent in control and SAH rats. Thus an increased rate of cGMP hydrolysis by PDE V may be a major factor contributing to the impairment of NO-mediated cerebral vasodilatation after SAH.
Sobey
C G
CG
Department of Pharmacology, The University of Melbourne, Parkville, Victoria 3052, Australia. c.sobey@pharmacology.unimelb.edu.au
Quan
L
L
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011688:Purinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517384:Pde5a protein, rat; C011145:zaprinast; D000109:Acetylcholine