Blockade of ATP-sensitive potassium channels in cerebral arterioles inhibits vasoconstriction from hypocapnic alkalosis in cats.

Abstract

BACKGROUND AND PURPOSE:

Recent studies have shown that the cerebral arteriolar dilation from hypercapnic acidosis is blocked by agents which inhibit KATP channels. These findings suggested that this response is due to opening of KATP channels. Because the repose to CO2 is a continuum, with hypercapnic acidosis causing vasodilation and hypocapnic alkalosis causing vasoconstriction, it would be expected that the response to hypocapnic alkalosis would be due to closing of KATP channels. There are no studies of the effect of inhibition of KATP channels on the response to hypocapnic alkalosis.

METHODS:

We investigated the effect of 3 agents that in earlier studies were found to inhibit KATP channels--NG-nitro-L-arginine, hydroxylysine, and glyburide--on the cerebral arteriolar constriction caused by graded hypocapnia induced by hyperventilation in anesthetized cats equipped with cranial windows.

RESULTS:

Hypocapnic alkalosis caused dose-dependent vasoconstriction that was inhibited completely by each of the 3 inhibitors of KATP channels. The blockade induced by these agents was eliminated in the presence of topical L-lysine (5 micromol/L).

CONCLUSIONS:

The findings show that agents which inhibit ATP-sensitive potassium channels in cerebral arterioles inhibit the vasoconstriction from hypocapnic alkalosis. These and earlier results showing that inhibition of KATP channels inhibited dilation from hypercapnic acidosis demonstrate that the response to CO2 in cerebral arterioles is mediated by the opening and closing of KATP channels.

• Authors: E P Wei, H A Kontos
• Journal: Stroke (Stroke) Vol. 30 Issue 4 Pg. 851-3; discussion 854 (Apr 1999) ISSN: 0039-2499 [Print] United States
• PMID: 10187890 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Hypoglycemic Agents
• Potassium Channel Blockers
• Carbon Dioxide
• Nitroarginine
• Hydroxylysine
• Adenosine Triphosphate
• Glyburide

Topics

• Adenosine Triphosphate (physiology)
• Alkalosis (physiopathology)
• Anesthesia
• Animals
• Arterioles (chemistry, physiology)
• Carbon Dioxide (blood)
• Cats
• Cerebral Arteries (chemistry, physiology)
• Cerebrovascular Circulation (drug effects)
• Glyburide (pharmacology)
• Hydroxylysine (pharmacology)
• Hypocapnia (physiopathology)
• Hypoglycemic Agents (pharmacology)
• Microcirculation (drug effects)
• Nitroarginine (pharmacology)
• Potassium Channel Blockers
• Vasoconstriction (drug effects)