title: Glycopyrrolate abolishes the exercise-induced increase in cerebral perfusion in humans.
abstract: Brain blood vessels contain muscarinic receptors that are important for cerebral blood flow (CBF) regulation, but whether a cholinergic receptor mechanism is involved in the exercise-induced increase in cerebral perfusion or affects cerebral metabolism remains unknown. We evaluated CBF and cerebral metabolism (from arterial and internal jugular venous O(2), glucose and lactate differences), as well as the middle cerebral artery mean blood velocity (MCA V(mean); transcranial Doppler ultrasound) during a sustained static handgrip contraction at 40% of maximal voluntary contraction (n = 9) and the MCA V(mean) during ergometer cycling (n = 8). Separate, randomized and counterbalanced trials were performed in control (no drug) conditions and following muscarinic cholinergic receptor blockade by glycopyrrolate. Glycopyrrolate increased resting heart rate from approximately 60 to approximately 110 beats min(-1) (P < 0.01) and cardiac output by approximately 40% (P < 0.05), but did not affect mean arterial pressure. The central cardiovascular responses to exercise with glycopyrrolate were similar to the control responses, except that cardiac output did not increase during static handgrip with glycopyrrolate. Glycopyrrolate did not significantly affect cerebral metabolism during static handgrip, but a parallel increase in MCA V(mean) (approximately 16%; P < 0.01) and CBF (approximately 12%; P < 0.01) during static handgrip, as well as the increase in MCA V(mean) during cycling (approximately 15%; P < 0.01), were abolished by glycopyrrolate (P < 0.05). Thus, during both cycling and static handgrip, a cholinergic receptor mechanism is important for the exercise-induced increase in cerebral perfusion without affecting the cerebral metabolic rate for oxygen.
authors.affiliation: Department of Anaesthesia, The Copenhagen Muscle Research Centre, University of Copenhagen, Copenhagen Ø, Denmark. tseifert78@gmail.com
authors.forename: Thomas
authors.initials: T
authors.lastname: Seifert
authors.forename: James P
authors.initials: JP
authors.lastname: Fisher
authors.forename: Colin N
authors.initials: CN
authors.lastname: Young
authors.forename: Doreen
authors.initials: D
authors.lastname: Hartwich
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Ogoh
authors.forename: Peter B
authors.initials: PB
authors.lastname: Raven
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fadel
authors.forename: Niels H
authors.initials: NH
authors.lastname: Secher
mesh_terms: D000328:Adult; D001642:Bicycling; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure; D002302:Cardiac Output; D002536:Cerebral Arteries / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D015444:Exercise; D005260:Female; D006024:Glycopyrrolate / Q000008:administration & dosage*; D018737:Hand Strength; D006339:Heart Rate; D006801:Humans; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage*; D009119:Muscle Contraction; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D013997:Time Factors; D017585:Ultrasonography, Doppler, Transcranial; D055815:Young Adult
chemical_list: D018727:Muscarinic Antagonists; D010100:Oxygen; D006024:Glycopyrrolate