Evidence that neuropeptide Y and norepinephrine mediate electrical field-stimulated vasoconstriction of rabbit middle cerebral artery.
We investigated the contractile response of isolated rabbit middle cerebral artery (MCA) segments to electrical field stimulation (EFS). The dynamics of the EFS contraction were compared with a similar-sized branch of rabbit ear artery. In comparison with the ear artery, the EFS contractions of the MCA displayed a longer latency and a higher stimulus frequency threshold. Greater stimulation train lengths were required to attain equilibrium, and the time course of EFS response--including force development, plateau, and return to rest tension--was significantly slower than in the ear artery. Morphological and pharmacological studies of the MCA showed that it receives sympathetic adrenergic innervation: whole-mount preparations displayed catecholamine histofluorescence; electron micrographs of MCA sections revealed a population of varicosities containing chromaffin positive large and small vesicles; and EFS contractions were blocked by tetrodotoxin (30 nM) and guanethidine (5 microM) and by chronic surgical sympathectomy. Exposure to prazosin (10 microM) or phenoxybenzamine (1 microM) blocked norepinephrine contractions but did not significantly influence the EFS contraction. Procedures and drugs that antagonized the responses to neuropeptide Y, serotonin, or histamine were also ineffective in blocking the EFS contraction. The involvement of ATP could not be assessed, since the purinergic P2 agonist alpha,beta-methylene ATP was ineffective in blocking ATP-mediated contractions. The EFS contraction, however, could be blocked by a combination of neuropeptide Y desensitization and phenoxybenzamine (30 nM) or prazosin (0.1 microM). These results suggest that norepinephrine and neuropeptide Y are released from sympathetic nerves and mediate EFS contraction by occupation of postjunctional alpha-adrenoceptor and neuropeptide Y receptors. Since the blockade of only one of these components does not diminish the response to EFS, the adrenergic neuroeffector system in this artery may involve complex prejunctional regulatory mechanisms.
Van Riper
D A
DA
Department of Pharmacology, University of Vermont, College of Medicine, Burlington 05405.
Bevan
J A
JA
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002536:Cerebral Arteries / Q000502:physiology* / Q000648:ultrastructure; D004558:Electric Stimulation / Q000379:methods; D006633:Histamine Antagonists / Q000494:pharmacology; D008854:Microscopy, Electron; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000502:physiology*; D011817:Rabbits; D011930:Reaction Time; D012702:Serotonin Antagonists / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D006633:Histamine Antagonists; D009478:Neuropeptide Y; D018377:Neurotransmitter Agents; D012702:Serotonin Antagonists; D013566:Sympathomimetics; D009638:Norepinephrine