The ATP-sensitive K+ channel mediates hypotension in endotoxemia and hypoxic lactic acidosis in dog.

Abstract

Endotoxemia causes hypotension characterized by vasodilation and resistance to vasopressor agents. The molecular mechanisms responsible for these changes are unclear. The ATPregulated K+ (KATP) channel has recently been found to be an important modulator of vascular smooth muscle tone which may transduce local metabolic changes into alterations ofvascular flow. We report here that in endotoxic hypotension, the sulfonylurea glyburide, a specific inhibitor for the KATP channel, caused vasoconstriction and restoration of blood pressure. Glyburide also induced vasoconstriction and restoration of blood pressure in the vasodilatory hypotension caused by hypoxic lactic acidosis, while it was ineffective in the hypotension induced by sodium nitroprusside. Thus, vasodilation and hypotension in septic shock are, at least in part, due to activation of the KATP channel in vascular smooth muscle, and anaerobic metabolism with acidosis is a sufficient stimulus for channel activation. Because anaerobic metabolism and acidosis are common features in shock ofany etiology, sulfonylureas may be effective therapeutic agents in the treatment of shock. (J. Clin.

Nitric oxide hyperpolarizes rabbit mesenteric arteries via ATP‐sensitive potassium channels.

“…Other studies indicate that hypoxia may activate KATP channels in part by decreasing the ATP:ADP ratio of VSM (Landry & Oliver, 1992). Therefore, a determination of whether NO activates KATP channels by decreasing their sensitivity to inhibition by ATP may be the key to understanding the role of NO in hypoxic tissue.…”

Vascular biology in sepsis: pathophysiological and therapeutic significance of vascular dysfunction

“…Particular attention has been focused on the involvement of KATP channels in both hypotension and vascular hyporeactivity induced by endotoxemia. In vivo evidence for KATP channel involvement in sepsis comes mainly from anesthetized rat (Wu et al, 1995;Sorrentino et al, 1999), dog (Landry and Oliver, 1992), and pig (Vanelli et al, 1995(Vanelli et al, , 1997) models of endotoxemia. Rapid restoration of blood pressure can be achieved with glibenclamide, resulting largely from increased systemic vascular resistance rather than improved cardiac output (Landry and Oliver, 1992;Vanelli et al, 1995).…”

“…In vivo evidence for KATP channel involvement in sepsis comes mainly from anesthetized rat (Wu et al, 1995;Sorrentino et al, 1999), dog (Landry and Oliver, 1992), and pig (Vanelli et al, 1995(Vanelli et al, , 1997) models of endotoxemia. Rapid restoration of blood pressure can be achieved with glibenclamide, resulting largely from increased systemic vascular resistance rather than improved cardiac output (Landry and Oliver, 1992;Vanelli et al, 1995). Glibenclamide also increases vasopressor reactivity to α1-adrenergic agonists in both the early phase (3 h) and the delayed phase (24 h from LPS challenge) of septic shock in the rat (Wu et al, 1995;Sorrentino et al, 1999).…”

A study of lactate and pyruvate levels as reliable indicator of impaired tissue perfusion

“…[2][3][4][5][6][7][8] Fiddian-Green reported similar change and stated that increase in lactate level is a reliable marker for impaired tissue perfusion. 9,10 It can be used as a prognostic indicator in patients presenting with features of impaired tissue perfusion.…”