Effects of glibenclamide on systemic and splanchnic haemodynamics in conscious rats

Abstract

1 The effects of the sulphonylurea, glibenclamide (20 mg kg ', i.v.), at a dose that blocks vascular potassium channels, on systemic and splanchnic haemodynamics (radioactive microspheres) were studied in conscious rats. 2 Glibenclamide significantly decreased cardiac index and hepatic artery blood flow while it significantly increased vascular resistance in systemic, portal and hepatic arterial territories. 3 In rats with suppressed cardiovascular reflexes, glibenclamide induced vasoconstriction in systemic, portal and hepatic arterial territories. 4 Intracerebroventricular administration of glibenclamide did not alter systemic or regional vascular tone.5 Glibenclamide blunted the vasodilator effect of the potassium channel opener, diazoxide but not that of the L-type calcium channel blocker, nicardipine. 6 Another sulphonylurea, glipizide (20 mg kg-', i.v.), induced significant systemic and splanchnic vasoconstriction. 7 Thus, the glibenclamide-induced blockade of vascular potassium channels caused a vasoconstriction in the systemic and splanchnic vascular beds. In these territories, therefore, the opening of glibenclamide-sensitive potassium channels might be responsible for a basal vasodilator tone.

The effects of dietary fish oil on exercising skeletal muscle vascular and metabolic control in chronic heart failure rats

“…The finding that GLI increased MAP with a consequent decrease in HR is not surprising as this is consistent with previous reports in rats (Moreau et al 1994, Gardiner et al 1996, swine (Duncker et al 2001) and humans (Farouque et al 2003). Specifically, the higher MAP and lower HR at rest with K ATP channel blockade were coincident with large reductions in renal and splanchnic VC.…”

“…Specifically, the higher MAP and lower HR at rest with K ATP channel blockade were coincident with large reductions in renal and splanchnic VC. This is in agreement with studies demonstrating a significant contribution of K ATP channels to basal vasomotor tone in the systemic circulation of conscious rats (Gardiner et al 1996, Moreau et al 1994, Parekh and Zou 1996, hamsters (Jackson et al 1993, Saito et al 1996 and dogs (Vanelli andHussain 1994, Comtois et al 1994). …”

KATP Channels and Pancreatic Islet Blood Flow in Anesthetized Rats

“…Thus, depending on the dose, glibenclamide is known to reduce early and peak vasodilatation following reactive hyperemia in humans (39). Furthermore, glibenclamide (20 mg/kg) to rats increased vascular resistance and caused a systemic vasoconstriction (40). Therefore, it seems as if K ATP channel closers would favor a vasoconstriction rather than a dilation.…”

The involvement of ATP‐sensitive potassium channels and adenosine in the regulation of coronary flow in the isolated perfused rat heart

“…Furthermore, haemodynamic data from conscious rats indicate that glibenclamide produces regional increases in vascular resistance (Moreau et al, 1994), which suggests that KATP also regulates vascular tone in vivo and in beds other than the coronary vasculature. Despite these observations there are several studies which do not support a role for KATP in the control of basal vascular tone under normal conditions (for reviews see Nichols & Lederer, 1991;Nelson & Quayle, 1995), and only contribute during metabolic impairment (Randall, 1994).…”