Amiloride-sensitive pressure-induced myogenic contraction in rat cerebral artery.
The inhibitory action of amiloride on the pressure-induced contraction was assessed in isolated rat cerebral artery. The artery was mounted in an arteriograph, and the change in intracellular Ca2+ concentration ([Ca2+]i) and vessel diameter were simultaneously measured. The contractile response elicited by intraluminal pressurization was independent of endothelium, i.e. myogenic in nature, and abolished by nicardipine, a Ca2+ antagonist or by removal of extracellular Ca2+, and was potentiated by 25 mM KCl. Cyclopiazonic acid and thapsigargin, inhibitors of the Ca2+-ATPase pump of the sarcoplasmic reticulum, and a protein kinase C inhibitor calphostin C did not suppress the pressure-induced contraction. Amiloride, a putative stretch-activated cation channel blocker, attenuated with an IC50 (50% inhibitory concentration) of about 3 microM the increase in [Ca2+]i and contractile activity in response to pressure, whereas the drug showed no apparent effect on the contraction produced by high KCl or 9,11-dideoxy-11alpha,9alpha-epoxymethano prostaglandin F2alpha (U46619). Furthermore, amiloride (100 microM) did not significantly affect intracellular pH in the artery. In spite of its multiple pharmacological actions, it seems possible that amiloride is a useful alternative tool at the cellular or tissue level to study the mechanotransduction mechanisms involved in the pressure-induced contraction in rat cerebral artery.
Oyabe
A
A
Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Shizuoka, Shizuoka City, Japan.
Masumoto
N
N
Ueta
K
K
Nakayama
K
K
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D004232:Diuretics / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000737:chemistry / Q000187:drug effects; D015640:Ion Channel Gating; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004232:Diuretics; D007473:Ion Channels; D014662:Vasoconstrictor Agents; C057360:5-(N,N-hexamethylene)amiloride; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000584:Amiloride