Regulatory Mechanism of Vascular Contractility by Extracellular K+ : Effect on Endothelium-Dependent Relaxation and Vascular Smooth Muscle Contractility / 대한흉부외과학회지

BACKGROUND: Extracellular K+ concentration ([K+]o) can be increased within several mM by the efflux of intracellular K+. To investigate the effect of an increase in [K+]o on vascular contractility, we attempted to examine whether extracellular K+ might modulate vascular contractility, endothelium-dependent relaxation (EDR) and intracellular Ca2+ concentration ([Ca2+]i) in endothelial cells (EC). MATERIAL AND METHOD: We observed isometric contractions in rabbit carotid, superior mesentery, basilar arteries and mouse aorta. [Ca2+]i was recorded by microfluorimeter using Fura-2/AM in EC. RESULT: No change in contractility was recorded by the increase in [K+]o from 6 to 12 mM in conduit artery such as rabbit carotid artery. whereas resistant vessels, such as basilar and branches of superior mesenteric arteries (SMA), were relaxed by the increase. In basilar artery, the relaxation by the increase in [K+]o from 1 to 3 mM was bigger than that by the increase from 6 to 12 mM. In contrast, in branches of SMA, the relaxation by the increase in [K+]o from 6 to 12 mM is bigger than that by the increase from 1 to 3 mM. Ba2 (30microM) did not inhibit the relaxation by the increase in [K+]o from 1 to 3 mM but did inhibit the relaxation by the increase from 6 to 12 mM. In the mouse aorta without the endothelium or treated with NG-nitro-L-arginine (30microM), nitric oxide synthesis blocker, the increase in [K+]o from 6 to 12 mM did not change the magnitude of contraction induced either norepinephrine or prostaglandin F2alpha. The increase in [K+]o up to 12 mM did not induce contraction of mouse aorta but the increase more than 12 mM induced contraction. In the mouse aorta, EDR was completely inhibited on increasing [K+]o from 6 to 12 mM. In cultured mouse aorta EC, [Ca2+]i was increased by acetylcholine or ATP application and the increased [Ca2+]i was reduced by the increase in [K+]o reversibly and concentration-dependently. In human umbilical vein EC, similar effect of extracellular K+ was observed. Ouabain, a Na+-K+ pump blocker, and Ni2 , a Na+-Ca2+ exchanger blocker, reversed the inhibitory effect of extracellular K+. CONCLUSION: In resistant arteries, the increase in [K+]o relaxes vascular smooth muscle and the underlying mechanisms differ according to the kinds of the arteries; Ba2 -insensitive mechanism in basilar artery and Ba2 -sensitive one in branches of SMA. It also inhibits [Ca2+]i increase in EC and thereby EDR. The initial mechanism of the inhibition may be due to the activation of Na+-K+ pump.

Extracellular K+ Effects on the Mouse Aortic Endothelial Cell Contractility / 대한흉부외과학회지

BACKGROUND: External stimuli increases intracellular (IC) Ca2+, which increases extracellular (EC) K+. To verify K+ effects on the vascular contraction, we performed an experiment using mouse aortic endothelial cell. MATERIAL AND METHOD: We examined the mouse aortic contractility changes as we measured the IC Ca2+ change and ionic current by using the voltage clamp technique under different conditions such as; increasing EC K+, removing endothelial cell, giving L-NAME (N-nitro-L-arginine methyl ester) which suppress nitric oxide formation, Ouabain which control Na+-K+ pump and Ni2+ which repress Na+-Ca2+ exchanger. RESULT: When we increased EC K+ from 6 to 12 mM, there was no change in aortic contractility. Aorta contracted with more than 12 mM of EC K+. Acetylcholine (ACh) induced relaxation was inhibited with EC K+ from 6 to 12 mM, but was not found after de- endothelialization or L-NAME treatment. ATP or ACh increased IC Ca2+ in cultured endothelium. After maximal increase of IC Ca2+, increasing EC K+ from 6 to 12 mM made IC Ca2+ decrease and re-decreasing EC K+ to 6 mM made IC Ca2+ increase. Ouabain and Ni2+ masked the inhibitory effect of endothelium dependent relaxation by increased EC K+. CONCLUSION: These data indicate that increase in EC K+ relaxes vascular smooth muscle and reduces Ca2+ in the endothelial cells which inhibit endothelium dependent relaxation. This inhibitory mechanism may be due to the activation of Na+-K+ pump and Na+-Ca2+ exchanger.