(Stroke. 1997;28:1264-1271.)
© 1997 American Heart Association, Inc.
Articles |
Role of Potassium Channels in Relaxations of Canine Middle Cerebral Arteries Induced by Nitric Oxide Donors
From the Departments of Anesthesiology and Pharmacology, Mayo Clinic and Mayo Foundation, Rochester, Minn.
Correspondence to Zvonimir S. Katusic, MD, PhD, Departments of Anesthesiology and Pharmacology, Mayo Clinic, Rochester, MN 55905.
Background and Purpose The mechanisms underlying smooth muscle relaxations of cerebral arteries in response to nitric oxide (NO) and cyclic GMP (cGMP) are still not completely understood. The present study was designed to determine the role of potassium channels in the relaxations to NO donors 3-morpholinosydnonimine (SIN-1) and sodium nitroprusside (SNP), as well as 8-bromo-3',5'-cGMP (a synthetic analogue of cGMP) and zaprinast (a selective cGMP phosphodiesterase inhibitor).
Methods Rings of canine middle cerebral arteries without endothelium were suspended in Krebs-Ringer bicarbonate solution for isometric tension recording. The levels of cGMP were measured by radioimmunoassay. Relaxations to NO donors 8-bromo-cGMP and zaprinast were studied in the presence and in the absence of K+ channel blockers charybdotoxin (large-conductance Ca2+-activated K+ channels), glyburide (ATP-sensitive K+ channels), 4-aminopyridine (delayed rectifier K+ channels), and BaCl2 (multiple types of K+ channels).
Results Concentration-dependent relaxations caused by NO donors (SIN-1 and SNP) were significantly reduced in arteries treated with BaCl2 (3x10-4 mol/L) or charybdotoxin (3x10-8 mol/L). Relaxations to 8-bromo-cGMP were not affected by the same concentrations of BaCl2 and charybdotoxin; however, they were reduced by higher concentrations of BaCl2 (3x10-3 mol/L) and charybdotoxin (10-7 mol/L). Zaprinast-induced relaxations were significantly reduced by BaCl2 (3x10-4 mol/L) or charybdotoxin (3x10-8 mol/L). Glyburide (10-5 mol/L) and 4-aminopyridine (10-3 mol/L) did not alter the relaxations to SIN-1 or SNP. The production of cGMP stimulated by SIN-1 in the vascular smooth muscle was not affected by BaCl2 (3x10-3 mol/L) or charybdotoxin (10-7 mol/L).
Conclusions These results indicate that in canine middle cerebral arteries, a significant portion of relaxations to NO liberated from nitrovasodilators is mediated by large-conductance Ca2+-activated K+ channels. Other K+ channels, sensitive to BaCl2, may also be involved in the mechanism of relaxations induced by NO.
Key Words: cerebral arteries • cyclic GMP • nitric oxide • vasodilation • dogs
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