Pharmacology of the mouse-isolated cerebral artery.
The routine availability of murine models of various cerebral circulatory disorders requires characterization of the regulation of cerebral artery tone in the mouse. Using vasoconstrictors and vasodilators with known efficacy in the cranial circulation of other species, we determined the pharmacological properties of the isolated pressurized mouse middle cerebral artery (MCA). The maximal pressure-induced myogenic constriction in isolated mouse MCA was 20.6+/-2.4%. Inhibition of nitric oxide (NO) and endothelin-1 (ET-1) altered the extent of pressure-induced myogenic tone. Isolated mouse MCA failed to either constrict or relax to 5-hydroxytryptamine (5-HT) and histamine; other vasoconstrictors demonstrated the following rank order of efficacy: ET-1>phenylephrine>U-46619. The rank order of endothelium-dependent vasodilator efficacy was bradykinin (BK)>acetylcholine (ACh)>substance P. The constriction produced by phenylephrine (PE) required a smaller increase in intracellular Ca(2+) elevation compared to constriction of a similar magnitude produced by membrane depolarization with potassium chloride (KCl). Pressure-induced myogenic tone (20-80 mm Hg) in mouse MCA was associated with smooth muscle cell membrane depolarization (-52.6+/-0.9 to -37.3+/-1.75 mV). Pressure-induced myogenic tone occurred with a smaller change in membrane potential compared to tone of a similar magnitude produced with KCl (-43.37+/-2.66 vs. -29.47+/-1.05 mV). The mouse MCA has a pharmacological profile that is distinct from other species including humans; however, similar to findings in other cerebral arteries, the mouse MCA shows intracellular sensitization to Ca(2+) following receptor activation.
Bai
Ni
N
Department of Pharmacology and Therapeutics, Faculty of Medicine, 2176 Health Sciences Mall, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
Moien-Afshari
Farzad
F
Washio
Hiroshi
H
Min
Anie
A
Laher
Ismail
I
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D002170:Canada; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D019332:Endothelin-1 / Q000494:pharmacology; D045604:Extracellular Fluid / Q000737:chemistry / Q000502:physiology; D005453:Fluorescence; D016257:Fura-2 / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D020768:Middle Cerebral Artery / Q000033:anatomy & histology / Q000187:drug effects* / Q000473:pathology*; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012965:Sodium Chloride; D013373:Substance P / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D019332:Endothelin-1; D010656:Phenylephrine; D013373:Substance P; D012965:Sodium Chloride; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine; D011188:Potassium; D001920:Bradykinin; D002118:Calcium; D016257:Fura-2; D019331:NG-Nitroarginine Methyl Ester