Karbon Monoksit, Spontan Hipertansif Sıçanların Renal Direnç Arterlerinde Vasküler Tonusun Düzenlenmesine Katkıda Bulunur

Year 2020, Volume: 77 Issue: 4, 421 - 430, 01.12.2020

Günnur Koçer Seher Nasırcılar Filiz Basralı Oktay Kuru Ümit Kemal Şentürk

Abstract

Amaç: Vasküler tonusun düzenlenmesinde yer alan karbon monoksit CO , hipertansiyon gelişimi sırasında kompansatuar etki gösterebilir. Bu çalışma, spontan hipertansif sıçanlarda SHR HO / CO sisteminin renal direnç arterlerinin vasküler tonusu üzerine etkilerini değerlendirmeyi amaçlamıştır.Yöntem: Renal direnç arterlerinde endojen CO’nun vasküler tonusa katkısı, bir HO inhibitörü varlığında ve yokluğunda fenilefrin Phe kontraksiyon yanıtı ile test edildi. Ekzojen CO gevşeme yanıtı da CO donörü Carbon monoxide-releasing molecule CORM kullanılarak değerlendirildi. CO gevşeme yanıtının mekanizması, guanilat siklaz inhibitörü ODQ veya potasyum kanal blokörü TEA ile değerlendirildi. Renal direnç arterlerindeki HO-1 ve HO-2 protein ekspresyonları Western blot analizi ile saptandı. Bulgular: SHR’lerde kontrol grubuna kıyasla Phe’ye verilen kasılma yanıtı anlamı olarak yüksekti p

Keywords

CO, HO-1, SHR, renal direnç arteri

Carbon Monoxide Contributes to The Regulation of Vascular Tonus in Renal Resistance Arteries in Spontaneously Hypertensive Rats

Abstract

Objective: Carbon monoxide CO , an end product of heme oxygenase HO involved in the regulation of vascular tone, may show a compensatory effect in the course of hypertension. This study aimed to assess the effects of the HO/CO system on the vascular tone of renal resistance arteries in spontaneously hypertensive rats SHRs .Methods: The contribution of endogenous CO to vascular tone in renal resistance arteries was evaluated by the phenylephrine Phe contraction response with or without an HO inhibitor. The effect of the exogenous CO relaxation response was assessed by a CO releasing molecule CORM . The mechanism of the CO relaxation effect was evaluated by a guanylate cyclase inhibitor, ODQ, or a potassium channel blocker, TEA. HO-1 and HO-2 enzyme protein expressions in renal resistance arteries were determined by Western blot analysis.Results: Phe-induced constriction responses were higher in renal resistance arteries of SHRs compared to control animals. The extent of the same type of constriction was even higher in the SHR group after inhibition of CO production. Relaxation responses to a CO donor, CORM, were greater in the SHR group versus the control group. TEA, but not ODQ, suppressed CORM olarak baskıladı p

Keywords

CO, HO-1, SHR, renal resistance artery

References

• Chan EC, Dusting GJ, Liu GS, Jiang F. Redox mechanisms of the beneficial effects of heme oxygenase in hypertension. J Hypertens. 2014;32(7):1379-86;87.
• Ndisang JF, Tabien HE, Wang R. Carbon monoxide and hypertension. J Hypertens. 2004;22(6):1057- 74.
• Botros FT, Prieto-Carrasquero MC, Martin VL, Navar LG. Heme oxygenase induction attenuates afferent arteriolar autoregulatory responses. Am J Physiol Renal Physiol. 2008;295(4):904-11.
• Botros FT, Navar LG. Interaction between endogenously produced carbon monoxide and nitric oxide in regulation of renal afferent arterioles. Am J Physiol Heart Circ Physiol. 2006;291(6):2772-8.
• Ushiyama M, Morita T, Katayama S. Carbon monoxide regulates blood pressure cooperatively with nitric oxide in hypertensive rats. Heart Vessels. 2002;16(5):189-95.
• Kim YM, Pae HO, Park JE, Lee YC, Woo JM, Kim NH, et al. Heme oxygenase in the regulation of vascular biology: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal. 2011;14(1):137-67.
• Thorup C, Jones CL, Gross SS, Moore LC, Goligorsky MS. Carbon monoxide induces vasodilation and nitric oxide release but suppresses endothelial NOS. Am J Physiol. 1999;277:882-9.
• Rodriguez F, Zhang F, Dinocca S, Nasjletti A. Nitric oxide synthesis influences the renal vascular response to heme oxygenase inhibition. Am J Physiol Renal Physiol. 2003;284(6):1255-62.
• Zou AP, Billington H, Su N, Cowley AW, Jr. Expression and actions of heme oxygenase in the renal medulla of rats. Hypertension. 2000;35:342-7.
• Aizawa T, Ishizaka N, Taguchi J, Nagai R, Mori I, Tang SS, et al. Heme oxygenase-1 is upregulated in the kidney of angiotensin II-induced hypertensive rats : possible role in renoprotection. Hypertension. 2000;35(3):800-6.
• Arregui B, Lopez B, Garcia Salom M, Valero F, Navarro C, Fenoy FJ. Acute renal hemodynamic effects of dimanganese decacarbonyl and cobalt protoporphyrin. Kidney Int. 2004;65(2):564-74.
• O’Donaughy TL, Walker BR. Renal vasodilatory influence of endogenous carbon monoxide in chronically hypoxic rats. Am J Physiol Heart Circ Physiol. 2000;279(6):2908-15.
• Wiesel P, Patel AP, Carvajal IM, Wang ZY, Pellacani A, Maemura K, et al. Exacerbation of chronic renovascular hypertension and acute renal failure in heme oxygenase-1-deficient mice. Circ Res. 2001;88(10):1088-94.
• Pradhan A, Umezu M, Fukagawa M. Heme- oxygenase upregulation ameliorates angiotensin II- induced tubulointerstitial injury and salt-sensitive hypertension. Am J Nephrol. 2006;26(6):552-61.
• Jadhav A, Torlakovic E, Ndisang JF. Hemin therapy attenuates kidney injury in deoxycorticosterone acetate-salt hypertensive rats. Am J Physiol Renal Physiol. 2009;296(3):521-34.