Zanzinger J, Czachurski J, Seller H
I. Physiologisches Institut, Universität Heidelberg, Im Neuenheimer Feld 326, D-69120 Heidelberg, Germany.
Pflugers Arch. 1996 Aug;432(4):671-7. doi: 10.1007/s004240050184.
Effects of inhibition of calcium-dependent potassium channels (K+Ca channels) on the regulation of arterial and venous tone by nitric oxide (NO) were studied in anaesthetized pigs following vagotomy and blockade of autonomic ganglia. Selective inhibition of K+Ca channels by charybdotoxin (CTX, 2 microg/kg iv) or iberiotoxin (IbTX, 1 microgram/kg) significantly augmented mean total peripheral resistance (TPR) to levels 30-60% above control. Venous and pulmonary vascular tone were assessed by changes in effective compliances of the venous (EVC) and pulmonary (EPC) vascular beds as calculated from changes in central venous and diastolic pulmonary arterial blood pressure during haemorrhagia (-5 ml/kg) and hypervolaemia (+5 ml/kg). Blockade of K+Ca channels significantly decreased both EVC (-20 to -30%) and EPC (-30 to -50%). Both CTX and IbTX significantly diminished the vasodilation caused by the NO-donor S-nitroso-N-acetylpenicillamine (SNAP) both during control conditions and following experimental vasoconstriction induced by systemic inhibition of NO-synthesis by NG-nitro-L-arginine methyl ester (L-NAME) or infusion of vasoconstrictor agonists. Dilator effects of the adenosine 3',5'-cyclic monophosphate (cAMP)-dependent agonist adenosine were only slightly reduced. However, blockade of K+Ca channels did not increase vasoconstriction induced by L-NAME significantly. These results suggest that activation of vascular K+Ca channels is an important mechanism by which NO attenuates the constrictor tone of resistance and capacitance vessels in vivo.
在切断迷走神经并阻断自主神经节的麻醉猪中，研究了抑制钙依赖性钾通道（K⁺Ca通道）对一氧化氮（NO）调节动脉和静脉张力的影响。用蝎毒素（CTX，2微克/千克静脉注射）或埃博毒素（IbTX，1微克/千克）选择性抑制K⁺Ca通道，可使平均总外周阻力（TPR）显著增加至比对照高30 - 60%的水平。通过计算出血（-5毫升/千克）和血容量过多（+5毫升/千克）期间中心静脉压和舒张期肺动脉压的变化得出的静脉（EVC）和肺（EPC）血管床有效顺应性的变化来评估静脉和肺血管张力。阻断K⁺Ca通道显著降低了EVC（-20%至-30%）和EPC（-30%至-50%）。在对照条件下以及在通过NG-硝基-L-精氨酸甲酯（L-NAME）全身抑制NO合成或输注血管收缩激动剂诱导的实验性血管收缩后，CTX和IbTX均显著减弱了NO供体S-亚硝基-N-乙酰青霉胺（SNAP）引起的血管舒张。腺苷3',5'-环磷酸（cAMP）依赖性激动剂腺苷的舒张作用仅略有降低。然而，阻断K⁺Ca通道并未显著增加L-NAME诱导的血管收缩。这些结果表明，血管K⁺Ca通道的激活是NO在体内减弱阻力血管和容量血管收缩张力的重要机制。
