Modulation of vascular norepinephrine responsiveness by potassium channels in normal and portal hypertensive rats

Studies in recent years have provided evidence that opening of potassium channels on the plasma membrane of smooth muscle hyperpolarizes the membrane and induces vasodilatation. To date, 4 types of K + have been identified on vascular smooth muscle cells. These are voltage-dependent K +channels (K), Ca2+-activated K+-channels (K) , inward rectifying K +channels (Ka) and ATP-sensitive K+-channels (K~,~), In spite of the known existence of these various K+-channels on vascular smooth muscle, very little is known about the role of these channels as modulators of mesenteric vascular tone in normal and chronic portal hypertensive conditions. The present study was designed to test the role of K+-channels in the arterial norepinephrine (NE) hyporesponsiveness of chronic portal hypertension. Methods: Pre-hepatic portal hypertension (PH) was produced by portal vein stenosis. Sham operated animals served as controls (SHAM). Small mesenteric resistance arteries (A2) were dissected from the intestinalmesenteric border, cannulated with glass micropipettes and pressurized to 60 mm Hg. Vascular responses to incremental doses of norepinephrine (NE) were assessed after incubation with each of the following channel blockers: 4-Aminopyridine (4-AP, 3mM; Kv-blocker), Iberiotoxin (IBT, 100 nM; K -blocker), Barium Chloride (BaCI 2, 50 laM; K~-blocker) or Glibenclamide (GLB., 10 laM; KAw-blocker). Physiological Salt Solution (PSS) was used as a vehicle for all experiments. Results: The table presents the pD 2 values (-log[ECho]) for each of the experimental groups (*p < 0.05 from same group Vehicle; # p < 0.05 from same drug SHAM).