Arteriolar tone is determined by activity of ATP-sensitive potassium channels.
The role of ATP-sensitive potassium channels (KATP) in determining resting arteriolar tone and vasodilator reactivity was assessed in superfused, hamster microcirculatory beds studied via intravital microscopy. Under resting conditions, the selective KATP blocker, glibenclamide, produced concentration-dependent vasoconstriction in both the cheek pouch and the cremaster muscle. Concentration-related constriction of cheek pouch arterioles was also observed with tetrapentylammonium, although this agent appeared to have toxic effects on the microcirculation. Glibenclamide (2 microM) abolished arteriolar vasodilation to cromakalim and pinacidil over a concentration range (10 nM-1 microM) in which these agents are selective KATP agonists and also significantly inhibited adenosine-, carbacyclin-, and isoproterenol-induced vasodilation. In contrast, responses to other vasodilators were not significantly affected [methacholine, forskolin, and dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP)] or only slightly depressed (sodium nitroprusside). Thus the activity of KATP determines, in part, resting arteriolar tone in the hamster. Furthermore, vasodilators like adenosine, beta-adrenergic agonists, and prostacyclin appear to act through these ion channels by a mechanism that may not involve cAMP.
Jackson
W F
WF
Department of Biological Sciences, College of Arts and Sciences, Western Michigan University, Kalamazoo 49008.
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D001578:Benzopyrans / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D019806:Cromakalim; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D016210:Methacholine Chloride / Q000494:pharmacology; D009129:Muscle Tonus; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009132:Muscles / Q000098:blood supply; D009599:Nitroprusside / Q000494:pharmacology; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D000644:Quaternary Ammonium Compounds; D014665:Vasodilator Agents; D019806:Cromakalim; D016210:Methacholine Chloride; D009599:Nitroprusside; D005576:Colforsin; D003994:Bucladesine; C026678:carboprostacyclin; D020110:Pinacidil; D000255:Adenosine Triphosphate; C027435:tetrapentylammonium; D011464:Epoprostenol; D007545:Isoproterenol; D005905:Glyburide