Responses of cerebral arterioles in diabetic rats to activation of ATP-sensitive potassium channels.
The goal of this study was to determine whether responses of pial arterioles to activation of ATP-sensitive potassium channels are altered during diabetes mellitus. We measured changes in diameter of pial arterioles in vivo in nondiabetic and diabetic rats (streptozotocin; 50-60 mg/kg ip; studied 3-4 mo after streptozotocin) in response to RP52891, an activator of ATP-sensitive potassium channels. RP52891 (1.0 microM) dilated pial arterioles in nondiabetic rats by 16 +/- 1% but constricted pial arterioles in diabetic rats by 2 +/- 2% (means +/- SE; P < 0.05 vs. response in nondiabetic rats). Dilatation of pial arterioles in nondiabetic rats in response to RP52891 was inhibited by glibenclamide (1.0 microM) but was not altered by NG-monomethyl-L-arginine (1.0 microM), apamin (0.1 microM), or charybdotoxin (50 nM). Thus dilatation of pial arterioles in response to RP52891 appears to be due to activation of ATP-sensitive potassium channels and does not involve nitric oxide or calcium-activated potassium channels. To determine whether impaired dilatation of pial arterioles in response to RP52891 in diabetic rats was related to a nonspecific effect of diabetes mellitus on vasodilatation, we measured diameter of pial arterioles in nondiabetic and diabetic rats in response to nitroglycerin. Nitroglycerin (1.0 microM) dilated pial arterioles by 12 +/- 1% in nondiabetic rats and 16 +/- 2% in diabetic rats (P > 0.05). Thus impaired dilatation of pial arterioles in diabetic rats in response to RP52891 also is not related to a nonspecific effect of diabetes mellitus on vasodilatation.(ABSTRACT TRUNCATED AT 250 WORDS)
Mayhan
W G
WG
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198.
Faraci
F M
FM
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D010847:Picolines / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D011714:Pyrans / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019323:omega-N-Methylarginine
D010847:Picolines; D015221:Potassium Channels; D011714:Pyrans; D019323:omega-N-Methylarginine; C061043:aprikalim; D000255:Adenosine Triphosphate; D001120:Arginine; D005996:Nitroglycerin