Rhythmic smooth muscle activity in hamster aortas is mediated by continuous release of NO from the endothelium.
Hamster aortas display endothelium-dependent, agonist-induced rhythmic contractions. However, the mechanism responsible for these oscillations is not known. Therefore, we investigated the possible role of nitric oxide (NO) on phenylephrine-induced rhythmicity in rings and segments of thoracic aortas of the hamster. We found that hamster aortas release NO, as detected by activation of purified soluble guanylate cyclase. The release of NO was abolished by mechanical removal of the endothelium or by exposure of the vessels to NG-nitro-L-arginine (NAG), a stereospecific selective inhibitor of NO synthesis. Correlated with the tonic release of NO was an elevation in guanosine 3',5'-cyclic monophosphate (cGMP) content in the vessels that could also be abolished by removal of the endothelium or treatment with NAG. The same procedures inhibited phenylephrine-induced isometric tension or diameter oscillations. Rhythmicity could be restored by exposure to the nitrovasodilator sodium nitroprusside, which increased cGMP levels in the aortas, or by exposure to the permeant analogue of cGMP, 8-BrcGMP. The beta-adrenergic agonist isoproterenol, as well as the cAMP analogue dibutyryl cAMP, failed to produce rhythmic contractions in either preparation. These data indicate that endothelium-derived NO, which stimulates the production of cGMP in the vascular smooth muscle, is the signal that leads to the observed rhythmic oscillations in smooth muscle mechanical activity.
Jackson
W F
WF
Department of Biological Sciences, Western Michigan University, Kalamazoo 49008.
Mülsch
A
A
Busse
R
R
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D000242:Cyclic AMP; D006152:Cyclic GMP; D007545:Isoproterenol