Lead acetate deteriorates the improvement effect of L-arginine and tetrahydrobiopterin on endothelin-1 receptors activity in rat aorta
Main Article Content
Abstract
Endothelin-1 (ET-1) is a potent vasoconstrictor hormone that has been identified as an important factor
responsible for the development of cardiovascular dysfunctions. ET-1 exerts its vasoconstrictor activity
through two pharmacologically distinct receptors, ETA and ETB that are found in vascular smooth muscle
cells (VSMCs) and the vasodilator activity through an ETB receptor located on endothelial cells. This study
aimed to show the impact of 1µM L-arginine (LA), 100µM tetrahydrobiopterin (BH4), and their combined
effect on ET-1 activity in both lead-treated and lead-untreated rat aortic rings. This means, investigating how
endothelial dysfunction reverses the role of nitric oxide precursor and cofactor. In this study, Rat aortic rings
have been pre-incubated with BH4, LA and their combination. Subsequently, the aortic rings were preincubated with 200µM N-Nitro-L-arginine methyl ester (L-NAME) and 0.5µM BQ-123. Then, the vascular
response to cumulative doses of rat ET-1 was analyzed in each of the above-mentioned groups (LA, BH4, LA
& BH4, L-NAME, BQ-123), in the presence and absence of lead acetate 1µM Pb (C2H3O2)2. ET-1 efficacy and
potency were significantly decreased in the presence of LA, BH4, and LA and BH4 combination in the untreated
group, while it significantly increased in the presence of lead. In the second trial of experiments ET-1 efficacy
markedly decreased in BQ-123- incubated cells in both lead-treated and untreated aortic rings. In the presence
of lead, the efficacy of ET-1 was raised with the use of L-NAME. In conclusion, LA and BH4 can be considered
pharmacological agents to alter the potency of ET-1-induced vasoconstriction and concomitantly lower blood
pressure.
Received 25/6/2022
Revised 3/9/2022
Accepted 4/9/2022
Published Online First 20/3/2023
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
How to Cite
References
Yanagisawa M, Inoue A, Ishikawa T, Kasuya Y, Kimura S, Kumagaye S, et al. Primary structure, synthesis, and biological activity of rat endothelin, an endothelium-derived vasoconstrictor peptide. Proc Natl Acad Sci U S A. 1988; 85(18): 6964-7.
Kostov K. The Causal Relationship between Endothelin-1 and Hypertension: Focusing on Endothelial Dysfunction, Arterial Stiffness, Vascular Remodeling, and Blood Pressure Regulation. Life (Basel). 2021; 11(9): 1-16
Khudhur ZO, Maulood IM. L-arginine and tetrahydrobiopterin modulate endothelin-1A receptor activity in isolated rat aorta. Zanco J pure Appl Sci. 2019; 31(2): 101-8.
Jankowich M, Choudhary G. Endothelin-1 levels and cardiovascular events. Trends Cardiovasc Med. 2020; 30(1): 1-8.
Khidhir SM, Mahmud AM, Maulood IM. Association of Endothelin-I and A symmetric Dimethylarginine Levels with Insulin Resistance in Type-2 Diabetes Mellitus Patients. Baghdad Sci J. 2022; 19(1): 0055-.
Sugimoto K, Yokokawa T, Misaka T, Kaneshiro T, Yamada S, Yoshihisa A, et al. Endothelin-1 Upregulates Activin Receptor-Like Kinase-1 Expression via Gi/RhoA/Sp-1/Rho Kinase Pathways in Human Pulmonary Arterial Endothelial Cells. Front. Cardiovasc. Med. 2021; 8: 1-8
Torres Crigna A, Link B, Samec M, Giordano FA, Kubatka P, Golubnitschaja O. Endothelin-1 axes in the framework of predictive, preventive and personalised (3P) medicine. EPMA J . 2021; 12(3): 265-305.
Masaki T, Sawamura T. Endothelin and endothelial dysfunction. Proc Jpn Acad Ser B Phys Biol Sci. 2006; 82(1): 17-24.
Citi V, Martelli A, Gorica E, Brogi S, Testai L, Calderone V. Role of hydrogen sulfide in endothelial dysfunction: Pathophysiology and therapeutic approaches. J Adv Res. 2021; 27: 99-113.
McElwain CJ, Tuboly E, McCarthy FP, McCarthy CM. Mechanisms of Endothelial Dysfunction in Pre-eclampsia and Gestational Diabetes Mellitus: Windows Into Future Cardiometabolic Health? Front Endocrinol (Lausanne). 2020; 11(655): 1-19
Khaleel FM, N-Oda N, A Abed B. Disturbance of Arginase Activity and Nitric Oxide Levels in Iraqi Type 2 Diabetes Mellitus. Baghdad Sci J. 2018; 15(2): 189-91.
Tsoi MF, Lo CWH, Cheung TT, Cheung BMY. Blood lead level and risk of hypertension in the United States National Health and Nutrition Examination Survey 1999–2016. Sci Rep. 2021; 11(1): 3010.
Silveira EA, Lizardo JH, Souza LP, Stefanon I, Vassallo DV. Acute lead-induced vasoconstriction in the vascular beds of isolated perfused rat tails is endothelium-dependent. Braz J Med Biol Res. 2010; 43(5): 492-9.
Fiorim J, Ribeiro Júnior RF, Silveira EA, Padilha AS, Vescovi MV, de Jesus HC, et al. Low-level lead exposure increases systolic arterial pressure and endothelium-derived vasodilator factors in rat aortas. PLoS One. 2011; 6(2): e17117.
Jiang X, Xing X, Zhang Y, Zhang C, Wu Y, Chen Y, et al. Lead exposure activates the Nrf2/Keap1 pathway, aggravates oxidative stress, and induces reproductive damage in female mice. Ecotoxicol Environ Saf. 2021; 207: 111231.
Kietadisorn R. Drainage versus defense: The management of vascular leakage in cardiovascular diseases. 2018. Thesis, Maastricht University]. Ridderprint BV. https://doi.org/10.26481/dis.20180523rk .
Linsenmeier RA, Beckmann L, Dmitriev AV. Intravenous ketamine for long term anesthesia in rats. Heliyon. 2020; 6(12): e05686.
Khan M, Rolly NK, Al Azzawi TNI, Imran M, Mun B-G, Lee I-J, et al. Lead (Pb)-Induced Oxidative Stress Alters the Morphological and Physio-Biochemical Properties of Rice (Oryza sativa L.). Agronomy. 2021; 11(3): 409.
Dao VT, Elbatreek MH, Deile M, Nedvetsky PI, Güldner A, Ibarra-Alvarado C, et al. Non-canonical chemical feedback self-limits nitric oxide-cyclic GMP signaling in health and disease. Sci Rep. 2020; 10(1): 10012.
Koyama Y. Endothelin ETB Receptor-Mediated Astrocytic Activation: Pathological Roles in Brain Disorders. Int J Mol Sci. 2021; 22(9): 4333.
Schulz E, Gori T, Münzel T. Oxidative stress and endothelial dysfunction in hypertension. Hypertens Res. 2011; 34(6): 665-73.
Rosanò L, Spinella F, Bagnato A. The importance of endothelin axis in initiation, progression, and therapy of ovarian cancer. Am J Physiol Regul Integr Comp Physiol. 2010; 299(2): R395-404.
Rafnsson A, Matic LP, Lengquist M, Mahdi A, Shemyakin A, Paulsson-Berne G, et al. Endothelin-1 increases expression and activity of arginase 2 via ETB receptors and is co-expressed with arginase 2 in human atherosclerotic plaques. Atherosclerosis. 2020; 292: 215-23.
Bendall JK, Douglas G, McNeill E, Channon KM, Crabtree MJ. Tetrahydrobiopterin in cardiovascular health and disease. Antioxid Redox Signal. 2014; 20(18): 3040-77.
Feng Y, Feng Y, Gu L, Liu P, Cao J, Zhang S. The Critical Role of Tetrahydrobiopterin (BH4) Metabolism in Modulating Radiosensitivity: BH4/NOS Axis as an Angel or a Devil. Front Oncol. 2021; 11: 720632.
Milewski K, Czarnecka AM, Albrecht J, Zielińska M. Decreased Expression and Uncoupling of Endothelial Nitric Oxide Synthase in the Cerebral Cortex of Rats with Thioacetamide-Induced Acute Liver Failure. Int J Mol Sci. 2021; 22(13): 6662.
Costa D, Benincasa G, Lucchese R, Infante T, Nicoletti GF, Napoli C. Effect of nitric oxide reduction on arterial thrombosis. Scand Cardiovasc J. 2019; 53(1): 1-8.
Guerby P, Tasta O, Swiader A, Pont F, Bujold E, Parant O, et al. Role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia. Redox Biol. 2021; 40: 101861.
Jiang J, Valen G, Tokuno S, Thorén P, Pernow J. Endothelial dysfunction in atherosclerotic mice: improved relaxation by combined supplementation with L-arginine-tetrahydrobiopterin and enhanced vasoconstriction by endothelin. Br J Pharmacol. 2000; 131(7): 1255-61.
Gonçalves DA, Jasiulionis MG, Melo FHMd. The Role of the BH4 Cofactor in Nitric Oxide Synthase Activity and Cancer Progression: Two Sides of the Same Coin. Int J Mol Sci. 2021; 22(17): 9546.
Shimokawa H, Godo S. Nitric oxide and endothelium‐dependent hyperpolarization mediated by hydrogen peroxide in health and disease. Basic Clin Pharmacol Toxicol. 2020; 127(2): 92-101.
Rapoport RM. Acute nitric oxide synthase inhibition and endothelin-1-dependent arterial pressure elevation. Front Pharmacol. 2014; 5: 57.
D'Angelo G, Loria AS, Pollock DM, Pollock JS. Endothelin activation of reactive oxygen species mediates stress-induced pressor response in Dahl salt-sensitive prehypertensive rats. Hypertension. 2010; 56(2): 282-9.
Miyauchi T, Sakai S. Endothelin and the heart in health and diseases. Peptides. 2019; 111: 77-88.
Maguire JJ, Davenport AP. Endothelin receptors and their antagonists. Semin Nephrol. 2015; 35(2): 125-36.
Schiffrin EL. Does Endothelin-1 Raise or Lower Blood Pressure in Humans?. Nephron. 2018; 139(1): 47-50.
Stefanov G, Briyal S, Pais G, Puppala B, Gulati A. Relationship Between Oxidative Stress Markers and Endothelin-1 Levels in Newborns of Different Gestational Ages. Front Pediatr. 2020; 8: 279.