Banks M, Wei C M, Kim C H, Burnett J C, Miller V M
Department of Surgery, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Am J Physiol. 1996 Nov;271(5 Pt 2):H1907-11. doi: 10.1152/ajpheart.1996.271.5.H1907.
C-type natriuretic peptide (CNP) is an endothelium-derived peptide that shares structural homology with atrial natriuretic peptide (ANP). CNP causes greater endothelium-independent relaxations in veins compared with arteries. Relaxations to CNP in porcine coronary arteries are mediated by hyperpolarization of the smooth muscle membrane. Experiments were designed to investigate the mechanism(s) by which CNP causes relaxation in canine femoral veins. Rings of canine femoral veins without endothelium were suspended for measurement of isometric force in organ chambers. Concentration-response curves to CNP were obtained in veins contracted with either endothelin-1 (10(-8) M), KCl (40 mM), phenylephrine (10(-6) M) or prostaglandin F2 alpha (2 x 10(-6) M) in the absence and presence of BQ-123 (10(-6) M), NG-monomenthyl-L-arginine (L-NMMA; 10(-4) M), HS-142-1 (10(-5) M), methylene blue (10(-5) M), or potassium channel blockers, tetraethylammonium chloride (TEA; 10(-3) M), charybdotoxin (10(-7) M), glibenclamide (10(-7) M), or apamin (10(-7) M). Relaxations to CNP were significantly attenuated when the tissue was contracted with KCl and endothelin-1. During contraction to either phenylephrine or prostaglandin F2 alpha, relaxations to CNP were inhibited by HS-142-1, methylene blue, TEA, and charybdotoxin, but not by L-NMMA, glibenclamide, or apamin. In separate experiments, guanosine 3',5'-cyclic monophosphate increased twofold within 10-60 s after the addition of CNP (10(-8) M). These data suggest that CNP mediates relaxation of canine femoral veins through activation of large-conduction, calcium-activated potassium channels and activation of particulate and soluble guanylate cyclase.
C型利钠肽（CNP）是一种内皮源性肽，与心房利钠肽（ANP）具有结构同源性。与动脉相比，CNP在静脉中引起的内皮非依赖性舒张作用更强。猪冠状动脉对CNP的舒张作用是由平滑肌膜超极化介导的。本实验旨在研究CNP引起犬股静脉舒张的机制。将无内皮的犬股静脉环悬挂于器官浴槽中以测量等长力。在不存在和存在BQ-123（10⁻⁶ M）、NG-单甲基-L-精氨酸（L-NMMA；10⁻⁴ M）、HS-142-1（10⁻⁵ M）、亚甲蓝（10⁻⁵ M）或钾通道阻滞剂氯化四乙铵（TEA；10⁻³ M）、蝎毒素（10⁻⁷ M）、格列本脲（10⁻⁷ M）或蜂毒明肽（10⁻⁷ M）的情况下，获得对用内皮素-1（10⁻⁸ M）、氯化钾（40 mM）、去氧肾上腺素（10⁻⁶ M）或前列腺素F2α（2×10⁻⁶ M）收缩的静脉的CNP浓度-反应曲线。当组织用氯化钾和内皮素-1收缩时，对CNP的舒张作用显著减弱。在用去氧肾上腺素或前列腺素F2α收缩期间，对CNP的舒张作用被HS-142-1、亚甲蓝、TEA和蝎毒素抑制，但不受L-NMMA、格列本脲或蜂毒明肽抑制。在单独的实验中，加入CNP（10⁻⁸ M）后10 - 60秒内，鸟苷3',5'-环磷酸增加了两倍。这些数据表明，CNP通过激活大电导钙激活钾通道以及颗粒性和可溶性鸟苷酸环化酶介导犬股静脉的舒张。
