Pulmonary vasoreactivity to endothelin-1 at elevated vascular tone is modulated by potassium channels.
The role of K+ channels on the pressor effect of endothelin-1 (ET-1) on vascular resistance and compliance in the canine pulmonary circulation was studied by using three different K+ channel inhibitors in isolated blood-perfused dog lungs when vascular tone was elevated with U-46619: 1) 10(-6) M glibenclamide, a potent and selective blocker of ATP-sensitive K+ channels; 2) 1 mM tetraethylammonium ions (TEA), an inhibitor of Ca(2+)-dependent K+ channels; and 3) 10(-4) M 4-aminopyridine, a nonspecific inhibitor of K+ channels. The results of the present study showed that under control vascular tone, 10(-8) M ET-1 increased total vascular resistance and capillary pressure by increasing postcapillary resistance. In addition, ET-1 decreased total vascular compliance. When vascular tone was elevated, ET-1 elicited an initial transient vasodilation followed by a sustained mild vasoconstriction that was lesser in magnitude than that observed under normal vascular tone. In addition, the increases in postcapillary resistance and capillary pressure and the decrease in vascular compliance that was observed with ET-1 at normal vascular tone was not present. Pretreatment with glibenclamide, TEA, and 4-aminopyridine at elevated vascular tone significantly potentiated the pressor effect of ET-1, and TEA blocked the transient vasodilation to ET-1. These data indicate that when pulmonary vasomotor tone is elevated with U-46619, Ca(2+)-dependent K+ channels may play a significant role in mediating the vasodilator response to ET-1 while ATP-sensitive, Ca(2+)-dependent, and other voltage-activated K+ channels attenuate the pulmonary vasoconstrictor response to ET-1.
Barman
S A
SA
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, USA.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008170:Lung Compliance / Q000187:drug effects / Q000502:physiology; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009929:Organ Size / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011651:Pulmonary Artery / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D016232:Endothelins; D015221:Potassium Channels; D014662:Vasoconstrictor Agents