Arshad Muhammad, Vijay Venkataramana, Floyd Beverly C, Marks Brian, Sarabu Mohan R, Wolin Michael S, Gupte Sachin A
Department of Physiology, New York Medical College, Westchester Medical Center, Valhalla, New York, USA.
Ann Thorac Surg. 2006 Jun;81(6):2147-54. doi: 10.1016/j.athoracsur.2006.01.024.
The internal mammary artery (IMA) and the radial artery (RA) are routinely used in coronary artery bypass grafting. However, RA grafts have a higher incidence of postoperative vasospasm and comparatively poor patency rates. The present study was undertaken to investigate the signaling pathways mediating contraction and relaxation in the IMA and RA with the aim of better understanding the mechanism underlying the propensity of RA grafts to spasm.
We examined the contractile responses of the IMA and RA to KCl (a depolarizing agent), phenylephrine (an alpha-adrenergic agonist), and U46619 (a thromboxane analogue).
Contractions induced by KCl or U46619 did not significantly differ in IMA and RA. By contrast, phenylephrine evoked significantly greater contraction of the IMA than the RA. Contractions induced by both phenylephrine and U46619 were dose-dependently inhibited by nifedipine (an L-type calcium channel blocker). Estimation of thromboxane A2 (TxA2) and prostacyclin (PGI2) synthesis revealed that the TxA2 to PGI2 ratio in the RA was twice that in the IMA. Moreover, acetylcholine-induced and nitroglycerin-induced relaxation of RA precontracted with U46619 was significantly impaired, as compared with RA precontracted with phenylephrine. These data suggest that inhibition of nitroglycerin-induced soluble guanylate cyclase activity by U46619 was at least partially responsible for the diminished vasodilatory response of RA to nitric oxide.
Our findings suggest that by reducing nitric oxide-stimulated soluble guanylate cyclase activity, the higher TxA2 to PGI2 ratios in RA, and the elevated serum TxA2 levels seen during coronary artery bypass grafting operations, may underlie the vasospasm and poor patency rates seen with the RA.
乳内动脉（IMA）和桡动脉（RA）常用于冠状动脉旁路移植术。然而，桡动脉移植物术后血管痉挛的发生率较高，通畅率相对较差。本研究旨在探讨介导乳内动脉和桡动脉收缩与舒张的信号通路，以便更好地理解桡动脉移植物易于痉挛的潜在机制。
我们检测了乳内动脉和桡动脉对氯化钾（一种去极化剂）、去氧肾上腺素（一种α-肾上腺素能激动剂）和U46619（一种血栓素类似物）的收缩反应。
氯化钾或U46619诱导的收缩在乳内动脉和桡动脉中无显著差异。相比之下，去氧肾上腺素引起的乳内动脉收缩明显强于桡动脉。硝苯地平（一种L型钙通道阻滞剂）剂量依赖性地抑制去氧肾上腺素和U46619诱导的收缩。血栓素A2（TxA2）和前列环素（PGI2）合成的评估显示，桡动脉中TxA2与PGI2的比值是乳内动脉的两倍。此外，与用去氧肾上腺素预收缩的桡动脉相比，U46619预收缩的桡动脉对乙酰胆碱诱导和硝酸甘油诱导的舒张明显受损。这些数据表明，U46619对硝酸甘油诱导的可溶性鸟苷酸环化酶活性的抑制至少部分导致了桡动脉对一氧化氮的血管舒张反应减弱。
我们的研究结果表明，通过降低一氧化氮刺激的可溶性鸟苷酸环化酶活性，桡动脉中较高的TxA2与PGI2比值以及冠状动脉旁路移植手术期间血清TxA2水平升高，可能是桡动脉出现血管痉挛和通畅率低的原因。
