Hammerer-Lercher Angelika, Fersterer Johann, Holzmann Sigrid, Bonatti Johannes, Ruttmann Elfriede, Hoefer Daniel, Mair Johannes, Puschendorf Bernd
Division of Clinical Biochemistry, Innsbruck Biocenter, Innsbruck Medical University, A-6020 Innsbruck, Austria.
Clin Sci (Lond). 2006 Sep;111(3):225-31. doi: 10.1042/CS20060034.
In the present study, we investigated the vasodilator properties of A-type, B-type and C-type natriuretic peptides (ANP, BNP and CNP respectively) and the NO (nitric oxide) donor sin-1 (3-morpholino-sydnonimine) in human by-pass grafts. In contrast with previous studies, the same vessel was used to demonstrate a direct link between cGMP production and functional relaxation. Remnants of the IMA (internal mammary artery) and SV (saphenous vein) were obtained from 82 patients undergoing coronary artery by-pass grafting. The responses to cumulative concentrations of ANP, BNP, CNP and sin-1 in vessel rings pre-contracted with a thromboxane A2 agonist (U46619) were measured in an organ bath. Additionally, intracellular cGMP production after single submaximal dose application of these drugs to vessel rings was determined by a RIA. ANP (P=0.001) and sin-1 (P<0.001) caused significant concentration-dependent relaxation of the IMA. In the SV, only sin-1 (P<0.001) induced marked concentration-dependent relaxation. At a single submaximal concentration, significant relaxation as well as intracellular cGMP production were found in response to ANP, BNP and sin-1 in the IMA. In contrast, in the SV, only sin-1 significantly induced cGMP production and relaxation. There was a moderate, but significant, correlation between intracellular cGMP net production and net relaxation in the IMA. In conclusion, ANP, as the most powerful relaxant of all the natriuretic peptides tested on the IMA, may be a possible alternative vasorelaxant to overcome peri-operative vasospasm in this artery. In contrast with sin-1, ANP and BNP were not effective vasorelaxants of the SV. Net relaxation in response to natriuretic peptides correlated with cGMP net concentrations in the IMA.
在本研究中，我们研究了 A 型、B 型和 C 型利钠肽（分别为心房钠尿肽、脑钠肽和 C 型钠尿肽）以及一氧化氮（NO）供体 SIN-1（3-吗啉代-西多芬）在人体旁路移植物中的血管舒张特性。与先前的研究不同，我们使用同一血管来证明环磷酸鸟苷（cGMP）生成与功能性舒张之间的直接联系。从 82 例行冠状动脉旁路移植术的患者获取胸廓内动脉（IMA）和大隐静脉（SV）的残余部分。在器官浴槽中测量用血栓素 A2 激动剂（U46619）预收缩的血管环对心房钠尿肽、脑钠肽、C 型钠尿肽和 SIN-1 累积浓度的反应。此外，通过放射免疫分析法（RIA）测定这些药物单次亚最大剂量应用于血管环后细胞内 cGMP 的生成。心房钠尿肽（P = 0.001）和 SIN-1（P < 0.001）引起胸廓内动脉显著的浓度依赖性舒张。在大隐静脉中，只有 SIN-1（P < 0.001）诱导出明显的浓度依赖性舒张。在单次亚最大浓度下，胸廓内动脉对心房钠尿肽、脑钠肽和 SIN-1 有显著舒张以及细胞内 cGMP 生成。相比之下，在大隐静脉中，只有 SIN-1 显著诱导 cGMP 生成和舒张。胸廓内动脉细胞内 cGMP 净生成与净舒张之间存在中度但显著的相关性。总之，在测试的所有利钠肽中，心房钠尿肽作为胸廓内动脉最有效的舒张剂，可能是克服该动脉围手术期血管痉挛的一种可能的替代血管舒张剂。与 SIN-1 不同，心房钠尿肽和脑钠肽不是大隐静脉有效的血管舒张剂。利钠肽引起的净舒张与胸廓内动脉中 cGMP 净浓度相关。
