Opposing actions of tolbutamide and glibenclamide on hypoxic pulmonary vasoconstriction.
1. We show that cromakalin and diazoxide, drugs that activate ATP-sensitive potassium (KATP) channels, abolish hypoxic pulmonary vasoconstriction (HPV) of isolated, perfused rat lungs. 2. Glibenclamide, an inhibitor of these channels, does not affect HPV, but it reverses the relaxation caused by cromakalim and diazoxide. 3. Tolbutamide, which has effects similar to glibenclamide in other tissues, paradoxically abolishes HPV, an effect reversed by glibenclamide. 4. These results suggest that: (i) pulmonary vessels contain KATP channels which are normally closed and are not opened by levels of hypoxia that cause constriction, (ii) tolbutamide acts on the pulmonary vasculature by a mechanism which differs from that of glibenclamide.
University Laboratory of Physiology, Oxford, UK.
B E
BE
Robertson
R Z
RZ
Kozlowski
P C
PC
Nye
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D003981:Diazoxide / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply*; D008297:Male; D015221:Potassium Channels / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D014044:Tolbutamide / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D014044:Tolbutamide; D003981:Diazoxide; D005905:Glyburide