We tested the hypothesis that constriction of cerebral arterioles during ac
ute increases in blood pressure is attenuated by activation of potassium (K
+) channels. We tested the effects of inhibitors of calcium-dependent K+ ch
annels [iberiotoxin (50 nM) and tetraethylammonium (TEA, 1 mM)] on changes
in arteriolar diameter during acute hypertension. Diameter of cerebral arte
rioles (baseline diameter = 46 +/- 2 mu m, 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 intrave
nous infusion of phenylephrine. Increases in arterial pressure from baselin
e to 130 and 150 mmHg decreased the diameter of cerebral arterioles by 5-10
%. Greater increases in arterial pressure produced large increases in arter
iolar diameter (i.e., "breakthrough of autoregulation''). Iberiotoxin or TE
A inhibited increases in arteriolar diameter when arterial pressure was inc
reased to 170 and 200 mmHg. The change in arteriolar diameter at 200 mmHg w
as 20 +/- 3% and -1 +/- 4% in the absence and presence of iberiotoxin, resp
ectively. These findings suggest that calcium-dependent K+ channels attenua
te cerebral microvascular constriction during acute increases in arterial p
ressure, and that increases in arteriolar diameter at high levels of arteri
al pressure are not simply a passive phenomenon.