In Vitro Effects of Nitroglycerin, Nicardipine, Verapamil, and Papaverine on Rabbit Brachial and Celiac Arterial Tone

혈관이완제의 전처치가 토끼의 상완동맥과 복강동맥의 혈관수축에 미치는 효과; Nitroglycerin, Nicardipine, Verapamil과 Papaverine의 비교

  • Shinn, Sung-Ho (Department of Thoracic and Cardiovascular Surgery, Hanyang University Guri Hospital, Hanyang University College of Medicine) ;
  • Kim, Young-Hak (Department of Thoracic and Cardiovascular Surgery, Hanyang University Hospital, Hanyang University College of Medicine) ;
  • Seo, Jung-Kuk (Department of Anesthesiology, Hanyang University Hospital, Hanyang University College of Medicine) ;
  • Kim, Jin-Hyuk (Department of Physiology, Hanyang University College of Medicine) ;
  • Chung, Won-Sang (Department of Thoracic and Cardiovascular Surgery, Hanyang University Hospital, Hanyang University College of Medicine) ;
  • Jeon, Yang-Bin (Department of Thoracic and Cardiovascular Surergy, Gil Hospital, Gachon University of Medicine and Science) ;
  • Chang, Byung-Chul (Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine) ;
  • Jang, Hyo-Jun (Department of Thoracic and Cardiovascular Surgery, Hanyang University Hospital, Hanyang University College of Medicine)
  • 신성호 (한양대학교 의과대학 구리병원 흉부외과학교실) ;
  • 김영학 (한양대학교 의과대학 서울병원 흉부외과학교실) ;
  • 서정국 (한양대학교 의과대학 서울병원 마취과학교실) ;
  • 김진혁 (한양대학교 의과대학 생리학과학교실) ;
  • 정원상 (한양대학교 의과대학 서울병원 흉부외과학교실) ;
  • 전양빈 (가천의과대학교 부속길병원 심장센터) ;
  • 장병철 (연세대학교 의과대학 흉부외과학교실) ;
  • 장효준 (한양대학교 의과대학 서울병원 흉부외과학교실)
  • Published : 2008.10.05

Abstract

Background: Vasoconstrictor-induced reduction in arterial graft diameter can cause significant flow deprivation. The aim of this study was to evaluate the effect of vasodilator pretreatment on vasoconstrictor-induced blood vessel spasm in vitro. Material and Method: Rabbit brachial arteries (BA) and celiac arteries (CA) were cut into rings $(3{\sim}4mm)$ and suspended with a force displacement transducer (TSD $125C^{(R)}$, Biopac Inc. USA) in a tissue bath filled with 5 mL modified Krebs solution bubbled with 5% $CO_2$ and 95% $O_2\;at\;38^{\circ}C$. The rings were contracted with vasoconstrictors, and the developed tension changes were considered control values. The rings were then pre- treated with $30{\mu}M$ nitroglycerin, nicardipine, verapamil, and papaverine, respectively, for 40 minutes and rinsed with the physiologic buffered salt solution three times every 15 min. The vasoconstrictor-induced tension changes after the previous procedure were considered experimental values. Data are expressed as the percentage tension induced by vasoconstrictors before and after pretreatment with vasodilators. Result: Nicardipine depressed vasoconstriction induced by norepinephrine, angiotensin II (All), and U46619 in both the BA and the CA more significantly than did nitroglycerin (p<0.01) and verapamil (p<0.05). Verapamil depressed vasoconstriction induced by 5-hydroxytryptamine (5HT), All, and U46619 in the BA and by 5HT in the CA more significantly than did nitroglycerin (p<0.01). Conclusion: These findings suggest that both nicardipine and verapamil effectively depressed vasoconstrictor action. Nicardipine is thought to be more effective than verapamil for the prevention of vasoconstrictor action.

배경: 혈관수축제에 의한 동맥 이식편 직경의 감소는 상당한 혈류감소를 야기할 수 있다. 본 연구는 체외에서 여러 가지 혈관수축제에 의해 유발되는 혈관경련에 대한 혈관이완제의 전처치 효과를 평가하기 위해 시행되었다. 대상 및 방법: 토끼의 상완동맥과 복강동맥으로부터 $3{\sim}4mm$ 길이의 환상 혈관절편을 제작하여 5% $CO_2$와 95% $O_2$가 통기되는 modified Krebs 용액$(38{\pm}0.5^{\circ}C)$이 담긴 tissue bath내에서 일측을 고정하고 다른 일측을 force displacement transducer (TSD $125C^{(R)}$, Biopac Inc. USA)에 연결한 후 혈관수축제를 투여하여, 이때 초래된 혈관의 장력 변화를 관찰하여 대조치로 하였다. 그 후 니트로글리세린(NTG), 니카디핀(Nica), 베라파밀(Vera) 그리고 파파베린(Papa)을 각각 $30{\mu}M$씩 40분간 전처치하였고, Krebs 용액을 15분마다 3차례 교환한 후 혈관수축제들을 연속적으로 투여하여 초래되는 혈관수축을 관찰하여 실험치로 하였으며 실험결과는 전처치 전과 후의 혈관수축제에 의해 야기된 장력의 백분율로써 표시되었다. 결과: Nica는 상완동맥과 복강동맥 모두에서 norepinephrine (NE), angiotensin II (AII), U46619에 의한 혈관수축을 NTG와 Vera보다 더 효과적으로 억제하였다(Nica vs NTG, p<0.01 ; Nica vs Vera, p<0.05). Vera의 혈관수축 억제 효과는 NTG와 비교하여 상완동맥에서는 5HT (5-hydrokytryptamine), AII, 및 U46619로 수축시킨 경우, 그리고 복강동맥에서는 5HT 수축시킨 경우에만 유의하였다(p<0.01). 결론: Nica와 Vera 둘 다 혈관수축제의 수축작용을 효과적으로 억제하였다. 특히 Nica는 Vera보다 혈관수축제의 작용을 예방하는데 더 효과적일 것으로 사료된다.

Keywords

References

  1. He GW, Yang CQ. "Vasoactivators"- a new concept for naturally secreted vasoconstrictor substances. Angiology 1994;45:265-71 https://doi.org/10.1177/000331979404500402
  2. He GW, Yang CQ, Starr A. Overview of the nature of vasoconstriction in arterial grafts for coronary operations. Ann Thorac Surg 1995;59:676-83 https://doi.org/10.1016/0003-4975(94)01011-0
  3. Cocks TM, Angus JA. Endothelium-dependent relaxation of coronary arteries by norepinephrine and serotonin. Nature 1983;305:627-30 https://doi.org/10.1038/305627a0
  4. Fukai T, Egashira K, Hata H, et al. Serotinin-induced coronary spasm in amodel. A minor role of defective endothelium-derived relaxing factor. Circulation 1993;88(part 1): 1922-30 https://doi.org/10.1161/01.CIR.88.4.1922
  5. He GW, Buxton B, Rosenfeldt F, et al. Weak $\beta$-adrenoceptor- mediated relaxation in the human internal mammary artery. J Thorac Cardiovasc Surg 1989;97:259-66
  6. Ohya Y, Sperelakis N. Involvement of a GTP-binding protein in stimulatingof angiotensin II on calcium channels in vascular smooth muscle cells. Circ Res 1991;68:763-71 https://doi.org/10.1161/01.RES.68.3.763
  7. Luescher TF, Boulanger CM, Dohi Y, et al. Endothelium- derived contracting factors. Hypertension 1992;19:117-30 https://doi.org/10.1161/01.HYP.19.2.117
  8. Davies GC, Sobel M, Salzman EW. Elevated plasma fibrinopeptide a andB2 levels during cardiopulmonary bypass. Circulation 1980;61:803-13
  9. Suma H. Spasm of the gastroepiploic artery graft. Ann Thorac Surg 1990;49:168-9 https://doi.org/10.1016/0003-4975(90)90390-R
  10. Reeves JG, Karp R, Buttner E, et al. Neural and adrenomedullary catecholamines release in response to cardiopulmonary bypass in man. Circulation 1982;66:49-54 https://doi.org/10.1161/01.CIR.66.1.49
  11. He GW, Rosenfeldt F, Buxton B, et al. Reactivity of human isolated internal mammary artery to constrictor and dilator agents. Implications for treatment of internal mammary artery spasm. Circulation 1989;80(suppl):I141-50
  12. Chavanon O, Cracowski JL, Hacini R, et al. Effect of topical vasodilators on gastroepiploic artery graft. Ann Thorac Surg 1999;67:1295-8 https://doi.org/10.1016/S0003-4975(99)00222-2
  13. Munzel T, Li H, Mollnau H, et al. Effects of long-term nitroglycerin treatment on endothelial nitric oxide synthase (NOS III) gene expression, NOS III-mediated superoxide production, and vascular NO bioavailability. Circ Res 2000; 86:7-12 https://doi.org/10.1161/01.RES.86.1.e7
  14. Acar C, Jebara VA, Portoghese M, et al. Revival of the radial artery for coronary bypass grafting. Ann Thorac Surg 1992;54:652-60 https://doi.org/10.1016/0003-4975(92)91007-V
  15. Reyes AT, Frame R, Brodman RF. Technique for harvesting the radial artery as a coronary artery bypass graft. Ann Thorac Surg 1995;59:118-26 https://doi.org/10.1016/0003-4975(94)00673-U
  16. Ali AT, William D, Montgomery BS, et al. Preventing gastroepiploic artery spasm: papaverine vs calcium channel blockade. J Surg Res 1997;71:41-8 https://doi.org/10.1006/jsre.1997.5138
  17. He GW, Shaw J, Yang CQ, et al. Inhibitory effects of glyceryl trinitrate on $\alpha$-adrenoceptor mediated contraction in the internal mammary artery. Br J Clin Pharmacol 1992;34: 236-43 https://doi.org/10.1111/j.1365-2125.1992.tb04130.x
  18. He GW, Yang CQ. Use of verapamil and nitroglycerin solution in preparation of radial artery for coronary grafting. Ann Thorac Surg 1996;61:610-4 https://doi.org/10.1016/0003-4975(95)00920-5
  19. Martin W, Furchgott RF, Villani GM. Phosphodiesterase inhibitors induce endothelium-dependent relaxation of rat and rabbit aorta by potentiating the effects of spontaneously released endothelium-derived relaxing factor. J Pharmacol Exp Ther 1986;237:539-47
  20. Brading AF, Burdyga TV, Scripnyuk ZD. The effects of papaverine on the electrical and mechanical activity of the guinea-pig ureter. J Physiol 1983;334:79-89 https://doi.org/10.1113/jphysiol.1983.sp014481
  21. He GW, Yang CQ. Radial artery has higher receptor- mediated contractility but similar endothelial function compared with mammary artery. Ann Thorac Surg 1997;63: 1346-52 https://doi.org/10.1016/S0003-4975(97)00106-9