title: Reduced production of cGMP underlies the loss of endothelium-dependent relaxations in the canine basilar artery after subarachnoid hemorrhage.
abstract: Endothelium-dependent relaxations are inhibited during chronic vasospasm after subarachnoid hemorrhage in the canine basilar artery, although the luminal release of endothelium-derived relaxing factor (EDRF) is maintained. The present study investigated the mechanisms underlying the impaired vascular reactivity and in particular whether the loss of responsiveness of the smooth muscle to EDRF is due to an impaired production of cGMP. Bradykinin and nitric oxide evoked concentration-dependent relaxations in isolated canine basilar arteries with and without endothelium, respectively, which were reduced in the subarachnoid hemorrhage group. Relaxations evoked by M&B22,948 (an inhibitor of cGMP phosphodiesterases) were smaller, but those evoked by the lipophilic cGMP analogue 8-bromo-cGMP were potentiated slightly in the subarachnoid hemorrhage group. The resting levels of cGMP in rings with endothelium (reflecting the effect of spontaneous release of EDRF) and those evoked by bradykinin in rings with endothelium and by nitric oxide in rings without endothelium were diminished in the subarachnoid hemorrhage group. These data indicate that the altered endothelium-mediated relaxations of the smooth muscle after subarachnoid hemorrhage is due, at least in part, to an impaired activation of soluble guanylate cyclase leading to a reduced production of cGMP in the smooth muscle.
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic, Rochester, Minn.
authors.forename: P
authors.initials: P
authors.lastname: Kim
authors.forename: V B
authors.initials: VB
authors.lastname: Schini
authors.forename: T M
authors.initials: TM
authors.lastname: Sundt
authors.forename: P M
authors.initials: PM
authors.lastname: Vanhoutte
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D001488:Basilar Artery / Q000378:metabolism* / Q000503:physiopathology; D001920:Bradykinin / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis*; D004285:Dogs; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D011863:Radioimmunoassay; D013345:Subarachnoid Hemorrhage / Q000378:metabolism* / Q000503:physiopathology; D014664:Vasodilation
chemical_list: D011688:Purinones; D009569:Nitric Oxide; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011145:zaprinast; D006152:Cyclic GMP; D001920:Bradykinin