Decreased ATP sensitivity of a K+ channel and enhanced vascular smooth muscle relaxation in genetically hypertensive rats.
OBJECTIVE
To characterize an ATP-sensitive K+ channel at the single-channel and tissue level in the vascular smooth muscle of normotensive and genetically hypertensive rats.


METHODS
Age- and sex-matched Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) were used. Patch-clamp single-channel recording was used to measure K+ channel activity in dissociated tail artery cells. The effect of the K+ channel-opener diazoxide and the specific ATP-sensitive K+ channel antagonist glyburide on isometric force development in isolated tail artery strips was determined by a standard muscle bath technique.


RESULTS
The concentration of ATP that caused half-maximal reduction in channel activity was greater in the SHRSP than in the WKY rats. Tail artery strips and cells from SHRSP were more sensitive to the effect of diazoxide on relaxation and channel activity, and less responsive to the effect of glyburide, than were those from WKY rats.


CONCLUSIONS
The decreased ATP sensitivity of this K+ channel may partly compensate for the increased vascular reactivity in hypertension, and the change in this property of the channel may be responsible for the altered sensitivity to diazoxide and glyburide in SHRSP.
Furspan
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PB
Department of Physiology, University of Michigan, Ann Arbor 48109-0622.
Webb
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D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002561:Cerebrovascular Disorders; D003981:Diazoxide / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012016:Reference Values; D013623:Tail / Q000098:blood supply; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D003981:Diazoxide; D005905:Glyburide