K_ATP‐channel‐induced vasodilation is modulated by the Na,K‐pump activity in rabbit coronary small arteries

Abstract

1 The purpose of the study was to evaluate the importance of the Na,K-pump in relaxations induced by K ATP -channel openers in rabbit coronary small arteries. 2 Arterial segments were mounted in myographs for recording of isometric tension. Whole-cell patch clamp was used to assess K ATP -channel currents in isolated smooth muscle cells from the arteries. 3 In arteries preconstricted with the thromboxane A 2 analogue U46619 pinacidil and cromakalim induced concentration-dependent relaxations. In arteries preconstricted with potassium (124 mM) only high concentrations of pinacidil had a small relaxant effect. 4 In arteries preconstricted with U46619 pinacidil-induced relaxations were unaffected by pretreatment with N o -nitro-L-arginine (L-NNA) and only slightly reduced after mechanical removal of the endothelium. 5 Pinacidil induced relaxations were not significantly affected by 1 mM glibenclamide. However, the relaxations were partly inhibited in potassium-free media and by 1 mM ouabain. 6 In contrast, the concentration-dependent relaxation to cromakalim was partly blocked by 1 mM glibenclamide and partly by 1 mM ouabain and when both drugs were present the inhibition increased. 7 Ouabain (1 mM) and glibenclamide (1 mM) each partly inhibited an ATP-sensitive current induced by pinacidil and cromakalim. In the presence of both inhibitors a greater inhibition was seen. When the solution in the patch pipette was sodium-free the current was reduced and ouabain had no effect. 8 The study suggests that the relaxation to cromakalim and most likely pinacidil is mediated through opening of K ATP channels. Inhibition of the Na,K-pump, however, may change the local environment for the K ATP channels (i.e. increases the ATP/ADPratio and/or decreases the transmembrane potassium gradient), which partly prevents the activation of the K ATP -channel current.

Contributions of A2Aand A2Badenosine receptors in coronary flow responses in relation to the KATPchannel using A2Band A2A/2Bdouble-knockout mice

“…Moreover, adenosine has been reported to activate K ATP channels in rabbit mesenteric arteries and isolated coronary artery SMCs (58,65). Others have demonstrated the presence of K ATP channels on coronary arteries and coronary artery SMCs (28,65) and their role in A 2A -induced effects in reactive hyperemia and retinal microvessel dilation (5,33,77). However, there are no reports, to our knowledge, suggesting the involvement of K ATP channels in A 2A AR-and A 2B ARinduced changes in mouse CF.…”

“…However, A 2B AR-induced vasodilatation is both nitric oxide dependent and independent in the mouse aortic conduit artery and coronary arteries, respectively (1,69). Although ATPsensitive K ϩ (K ATP ) channels have been shown to be present in coronary artery cells (28,65) and K ϩ channels, in general, are known to be involved in the A 2A AR and A 2B AR-mediated hyperpolarization of coronary arteries (31,39,52), the involvement of K ATP channels in adenosine-induced coronary artery responses remains poorly understood.…”

Interaction Between Na + /K + -Pump and Na + /Ca 2+ -Exchanger Modulates Intercellular Communication

“…We have previously demonstrated a functional interaction between ouabain-sensitive Na ϩ /K ϩ -pumps and K ATP channels. 37 In that study we found that the activity of ouabain-sensitive Na ϩ /K ϩ -pumps could modify the activity of the K ATP channels. The data in the present study suggest that K ATP channels provide K ϩ for the Na ϩ /K ϩ -pump under [K ϩ ] o -free conditions.…”

KATPChannels in the Cardiovascular System

“…This mode of regulation may become more pronounced with aging, since glycolytic inhibition in aged rat hearts causes action potential shortening and arrhythmias that can be prevented by K ATP channel block with glibenclamide (575). Competition for local glycolytically derived ATP may also be responsible for the known functional interaction between the K ATP channel and the Na ϩ /K ϩ pump, which has been observed in several tissues, including frog skin (829), neurons (8), the kidney (548), skeletal muscle (663), smooth muscle (269), and the heart (411,646). Although the physiological relevance of this functional interaction is obvious, it has been suggested to be important in the protective effects of ischemic preconditioning (IPC) (331).…”