Differential Contribution of Nerve-Derived Noradrenaline to High K⁺-Induced Contraction Depending on Type of Artery

Abstract

High K -induced contraction of arterial smooth muscle is thought to be mediated by membrane depolarization and subsequent activation of voltage-dependent Ca 2 channels (VDCCs). In line with this, this study found that contraction induced by 80 mM K was almost abolished by nifedipine (1 µM), a VDCC inhibitor, in isolated rat aorta, and was markedly suppressed in the iliac artery. However, nifedipine (1 µM) only partially suppressed high K -induced contraction in the tail artery. The contractions remaining in the arteries were further reduced by non-selective cation channel (NSCC) inhibitors, including 2-aminoethoxydiphenyl borate (2-APB) (100 µM), SK&F96365 (10 µM), and 3,4-dihydro-6,7-dimethoxy-α-phenyl-N,N-bis[2-(2,3,4-trimethoxyphenyl)ethyl]-1-isoquinolineacetamide hydrochloride (LOE908) (10 µM). In particular, sustained tonic contraction was nearly abolished. Prazosin (0.3 µM), an α 1 -adrenoceptor antagonist, partially inhibited high K -induced contraction in the tail and iliac arteries, but had no effect in the aorta. Consistently, tyramine potently induced contraction in the tail and iliac arteries, but not in the aorta. Furthermore, the inhibition by prazosin and NSCC inhibitors of the high K -induced contraction in the presence of nifedipine was comparable. These results suggest that depending on the type of artery, high K -induced contraction is mediated by Ca 2 influx not only through VDCCs but also through NSCCs, the activation of which is due to the activation of α 1 -adrenoceptors by the released noradrenaline from sympathetic nerve terminals resulting from high K stimulation. Key words high K +; tail artery; non-selective cation channel; voltage dependent calcium channel; noradrenaline Ca 2+ elevation in cytosol causes contraction in smooth muscle. In arterial smooth muscle, the primary pathways of Ca 2+ influx from extracellular space are through L-type voltagedependent Ca 2+ channels (VDCCs) and non-selective cation channels (NSCCs). 1) Elevating extracellular K + concentration decreases the K + gradient between the inside and outside of the cell membrane, which in turn causes cell membrane depolarization. VDCCs are activated by this depolarization, which leads to Ca 2+ influx, thereby causing smooth muscle contraction. Therefore, high K + stimulation is frequently used as an estimation of VDCC-mediated contraction.2) It is interesting to note, however, that our preliminary study showed insufficient inhibition of high K + -induced contraction by the VDCC inhibitor nifedipine in isolated rat tail artery. We thus further investigated the mechanism underlying high K + -induced contraction in different types of arteries, i.e., the aorta, and the iliac and tail arteries. The present data show that, depending on the type of artery, high K + -induced contraction is mediated not only through VDCCs but also through NSCCs activated by noradrenaline released from sympathetic nerve terminals. MATERIALS AND METHODS Measurement of ContractionProtocols for animal use were reviewed and approved by the Institutio...

Effects of Cardiotoxins from Naja oxiana Cobra Venom on Rat Heart Muscle and Aorta: A Comparative Study of Toxin-Induced Contraction Mechanisms

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