Potassium channels modulate cerebral autoregulation during acute hypertension.
We tested the hypothesis that constriction of cerebral arterioles during acute increases in blood pressure is attenuated by activation of potassium (K(+)) channels. We tested the effects of inhibitors of calcium-dependent K(+) channels [iberiotoxin (50 nM) and tetraethylammonium (TEA, 1 mM)] on changes in arteriolar diameter during acute hypertension. Diameter of cerebral arterioles (baseline diameter = 46 +/- 2 microm, mean +/- SE) was measured using a cranial window in anesthetized rats. Arterial pressure was increased from a control value of 96 +/- 1 mmHg to 130, 150, 170, and 200 mmHg by intravenous infusion of phenylephrine. Increases in arterial pressure from baseline to 130 and 150 mmHg decreased the diameter of cerebral arterioles by 5-10%. Greater increases in arterial pressure produced large increases in arteriolar diameter (i.e., "breakthrough of autoregulation"). Iberiotoxin or TEA inhibited increases in arteriolar diameter when arterial pressure was increased to 170 and 200 mmHg. The change in arteriolar diameter at 200 mmHg was 20 +/- 3% and -1 +/- 4% in the absence and presence of iberiotoxin, respectively. These findings suggest that calcium-dependent K(+) channels attenuate cerebral microvascular constriction during acute increases in arterial pressure, and that increases in arteriolar diameter at high levels of arterial pressure are not simply a passive phenomenon.
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Departments of Internal Medicine and Pharmacology, University of Iowa College of Medicine, Iowa City 52242, USA.
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D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D000208:Acute Disease; D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation; D006706:Homeostasis; D006973:Hypertension / Q000503:physiopathology*; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D019789:Tetraethylammonium / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D019789:Tetraethylammonium; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C064719:iberiotoxin; D015761:4-Aminopyridine