Cigarette smoking impairs Na+-K+-ATPase activity in the human coronary microcirculation

The extracellular K(+) concentration ([K(+)](o)) has been proposed to link cardiac metabolism with coronary perfusion and arrhythmogenesis, particularly during ischemia. Several animal studies have also supported K(+) as an EDHF that activates Na(+)-K(+)-ATPase and/or inwardly rectifying K(+) (K(ir)) channels. Therefore, we examined the vascular reactivity of human coronary arterioles (HCAs) to small elevations in [K(+)](o), the influence of risk factors for coronary disease, and the role of K(+) as an EDHF. Changes in the internal diameter of HCAs were recorded with videomicroscopy. Most vessels dilated to increases in [K(+)](o) with a maximal dilation of 55 ± 6% primarily at 12.5-20.0 mM KCl (n = 38, average: 16 ± 1 mM). Ouabain, a Na(+)-K(+)-ATPase inhibitor, alone reduced the dilation, and the addition of Ba(2+), a K(ir) channel blocker, abolished the remaining dilation, whereas neither endothelial denudation nor Ba(2+) alone reduced the dilation. Multivariate analysis revealed that cigarette smoking was the only risk factor associated with impaired dilation to K(+). Ouabain significantly reduced the vasodilation in HCAs from subjects without cigarette smoking but not in those with smoking. Cigarette smoking downregulated the expression of the Na(+)-K(+)-ATPase catalytic α(1)-subunit but not Kir2.1 in the vessels. Ouabain abolished the dilation in endothelium-denuded vessels to a same extent to that with the combination of ouabain and Ba(2+) in endothelium-intact vessels, whereas neither ouabain nor ouabain plus Ba(2+) reduced EDHF-mediated dilations to bradykinin and ADP. A rise in [K(+)](o) dilates HCAs primarily via the activation of Na(+)-K(+)-ATPase in vascular smooth muscle cells with a considerable contribution of K(ir) channels in the endothelium, indicating that [K(+)](o) may modify coronary microvascular resistance in humans. Na(+)-K(+)-ATPase activity is impaired in subjects who smoke, possibly contributing to dysregulation of the coronary microcirculation, excess ischemia, and arrhythmogenesis in those subjects. K(+) does not likely serve as an EDHF in the human coronary arteriolar dilation to bradykinin and ADP.

Medienart:	E-Artikel

Erscheinungsjahr:	2011
Erschienen:	2011

Enthalten in:	Zur Gesamtaufnahme - volume:300
Enthalten in:	American journal of physiology. Heart and circulatory physiology - 300(2011), 1 vom: 15. Jan., Seite H109-17

Sprache:	Englisch

Beteiligte Personen:	Miura, Hiroto [VerfasserIn] Toyama, Kazuyoshi [VerfasserIn] Pratt, Phillip F [VerfasserIn] Gutterman, David D [VerfasserIn]

Links:	Volltext

Themen:	5ACL011P69 Biological Factors EC 7.2.2.13 Endothelium-dependent hyperpolarization factor Journal Article Ouabain Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Sodium-Potassium-Exchanging ATPase

Anmerkungen:	Date Completed 28.01.2011 Date Revised 20.10.2021 published: Print-Electronic Citation Status MEDLINE

doi:	10.1152/ajpheart.00237.2010

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	NLM203613104