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Diabetes modifies the role of prostanoids and potassium channels which regulate the hypereactivity of the rabbit renal artery to BNP

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Abstract

Diabetic nephropathy is associated with increased risk of cardiovascular disease. B-type natriuretic peptide (BNP) plays an important role in cardiovascular pathophysiology and therapeutics. The aim of the present study was to investigate the influence of experimental diabetes on the mechanisms that regulate the relaxant response of the rabbit renal artery to BNP. Arterial relaxations to BNP were enhanced in diabetic rabbits. Indomethacin enhanced BNP-induced relaxation in control rabbits but showed no effect in diabetic rabbits. BNP-induced release of thromboxane A2 or prostacyclin was not different in both groups of animals. Iberiotoxin had no effect on relaxations to BNP in both groups of animals. Charybdotoxin displaced to the right the concentration-response curve to BNP in both group of animals, and inhibited BNP-induced relaxation only in diabetic rabbits. Glibenclamide did not modify the BNP-induced relaxations in control rabbits, but inhibited it in diabetic rabbits. These results suggest that diabetes induces hypereactivity of the rabbit renal artery to BNP by mechanisms that at least include (1) a reduced vasoconstrictor influence of arachidonic acid metabolites via cyclooxygenase 2, which is not related with changes in thromboxane A2 and prostacyclin release from the arterial wall and (2) a selectively increased modulatory activity of KATP and endothelial IKCa channels.

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References

  • Carmines PK (2010) The renal vascular response to diabetes. Curr Opin Nephrol Hypertens 19:85–90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carmines PK, Fujiwara K (2002) Altered electromechanical coupling in the renal microvasculature during the early stage of diabetes mellitus. Clin Exp Pharmacol Physiol 29:143–148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Centeno JM, Marrachelli VG, Miranda L, Castelló-Ruiz M, Burguete MC, Jover-Mengual T, Salom JB, Torregrosa G, Miranda FJ, Alborch E (2013) Involvement of prostacyclin and potassium channels in the diabetes-induced hyporeactivity of the rabbit carotid artery to B-type natriuretic peptide. Eur J Pharmacol 701:159–167

    Article  CAS  PubMed  Google Scholar 

  • Dong DL, Bai YL, Cai BZ (2016) Calcium-activated potassium channels: potential target for cardiovascular diseases. Adv Protein Chem Struct Biol 104:233–261

    Article  PubMed  Google Scholar 

  • Ellinsworth DC, Shukla N, Fleming I, Jeremy JY (2014) Interactions between thromboxane A2, thromboxane/prostaglandin (TP) receptors, and endothelium-derived hyperpolarization. Cardiovasc Res 102:9–16

  • Feng Y, Wang D, Bi H, Zhang H (2016) The role of natriuretic peptides in diabetes and its complications. Biomed Pharmacother 84:1826–1832

    Article  CAS  PubMed  Google Scholar 

  • Garland CJ, Dora KA (2017) EDH: endothelium-dependent hyperpolarization and microvascular signaling. Acta Physiol (Oxf) 219:152–161

    Article  CAS  Google Scholar 

  • Gokina NI, Bonev AD, Phillips J, Gokin AP, Veilleux K, Oppenheimer K, Goloman G (2015) Impairment of IKCa channels contributes to uteroplacental endothelial dysfunction in rat diabetic pregnancy. Am J Physiol Heart Circ Physiol 309:H592–H604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gruden G, Landi A, Bruno G (2014) Natriuretic peptides, heart, and adipose tissue: new findings and future developments for diabetes research. Diabetes Care 37:2899–2908

    Article  CAS  PubMed  Google Scholar 

  • Holcberg G, Kossenjans W, Brewer A, Miodovnik M, Myatt L (1995) The action of two natriuretic peptides (atrial natriuretic peptide and brain natriuretic peptide) in the human placental vasculature. Am J Obstet Gynecol 172:71–77

    Article  CAS  PubMed  Google Scholar 

  • Huang C, Pollock CA, Chen XM (2015) KCa3.1: a new player in progressive kidney disease. Curr Opin Nephrol Hypertens 24:61–66

    Article  CAS  PubMed  Google Scholar 

  • Hyman AL, De Witt BJ, Gumusel B, Hao Q, Kadowitz PJ, Lippton HL (2001) l-NAME enhances responses to atrial natriuretic peptide in the pulmonary vascular bed of the cat. J Appl Physiol (1985) 90:2101–2108

    Article  CAS  Google Scholar 

  • Liu Y, Xie A, Singh AK, Ehsan A, Choudhary G, Dudley S, Sellke FW, Feng J (2015) Inactivation of endothelial small/intermediate conductance of calcium-activated potassium channels contributes to coronary arteriolar dysfunction in diabetic patients. J Am Heart Assoc 4:e002062

    Article  PubMed  PubMed Central  Google Scholar 

  • Malek V, Gaikwad AB (2017) Neprilysin inhibitors: a new hope to halt the diabetic cardiovascular and renal complications? Biomed Pharmacother 90:752–759

    Article  CAS  PubMed  Google Scholar 

  • Marrachelli VG, Miranda FJ, Centeno JM, Burguete MC, Castelló-Ruiz M, Jover-Mengual T, Pérez AM, Salom JB, Torregrosa G, Alborch E (2010) Mechanisms involved in the relaxant action of testosterone in the renal artery from male normoglycemic and diabetic rabbits. Pharmacol Res 61:149–156

    Article  CAS  PubMed  Google Scholar 

  • Marrachelli VG, Centeno JM, Miranda I, Castelló-Ruiz M, Burguete MC, Jover-Mengual T, Salom JB, Torregrosa G, Miranda FJ, Alborch E (2012) Diabetes impairs the atrial natriuretic peptide relaxant action mediated by potassium channels and prostacyclin in the rabbit renal artery. Pharmacol Res 66:392–400

    Article  CAS  PubMed  Google Scholar 

  • Marrachelli VG, Miranda FJ, Centeno JM, Miranda I, Castelló-Ruiz M, Burguete MC, Jover-Mengual T, Salom JB, Torregrosa G, Alborch E (2011) Mechanisms underlying the diabetes-induced hyporeactivity of the rabbit carotid artery to atrial natriuretic peptide. Pharmacol Res 63:190–198

    Article  CAS  PubMed  Google Scholar 

  • McNeish AJ, Jimenez-Altayo F, Cottrell GS, Garland CJ (2012) Statins and selective inhibition of Rho kinase protect small conductance calcium-activated potassium channel function (KCa2.3) in cerebral arteries. PLoS One 7:e46735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakagawa O, Ogawa Y, Itoh H, Suga S, Komatsu Y, Kishimoto I, Nishino K, Yoshimasa T, Nakao K (1995) Rapid transcriptional activation and early mRNA turnover of brain natriuretic peptide in cardiocyte hypertrophy. Evidence for brain natriuretic peptide as an “emergency” cardiac hormone against ventricular overload. J Clin Invest 96:1280–1287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishikimi T, Kuwahara K, Nakao K (2011) Current biochemistry, molecular biology, and clinical relevance of natriuretic peptides. J Cardiol 57:131–140

    Article  PubMed  Google Scholar 

  • Otsuka K, Tanaka H, Horinouchi T, Koike K, Shigenobu K, Tanaka Y (2002) Functional contribution of voltage-dependent and Ca2+ activated K+ (BKCa) channels to the relaxation of guinea-pig aorta in response to natriuretic peptides. J Smooth Muscle Res 38:117–129

    Article  CAS  PubMed  Google Scholar 

  • Pandey KN (2008) Emerging roles of natriuretic peptides and their receptors in pathophysiology of hypertension and cardiovascular regulation. J Am Soc Hypertens 2:210–226

    Article  PubMed  PubMed Central  Google Scholar 

  • Potter LR, Abbey-Hosch S, Dickey DM (2006) Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. Endocr Rev 27:47–72

    Article  CAS  PubMed  Google Scholar 

  • Ronco C (2010) Cardiorenal syndromes: definition and classification. Contrib Nephrol 164:33–38

    Article  PubMed  Google Scholar 

  • Sabrane K, Kruse MN, Gazinski A, Kuhn M (2009) Chronic endothelium-dependent regulation of arterial blood pressure by atrial natriuretic peptide: role of nitric oxide and endothelin-1. Endocrinology 150:2382–2387

    Article  CAS  PubMed  Google Scholar 

  • Schach C, Resch M, Schmid PM, Riegger GA, Endemann DH (2014) Type 2 diabetes: increased expression and contribution of IKCa channels to vasodilation in small mesenteric arteries of ZDF rats. Am J Physiol Heart Circ Physiol 307:H1093–H1102

    Article  CAS  PubMed  Google Scholar 

  • Seki N, Nishimura M, Matsumoto T, Fukazawa M, Kenmochi T (2013) Relationship between BNP level and renal function in diabetic nephropathy with microalbuminuria. J Diabetes Complicat 27:92–97

    Article  PubMed  Google Scholar 

  • Seki N, Matsumoto T, Fukazawa M (2015) Relationship between the brain natriuretic peptide (BNP) level and remission of diabetic nephropathy with microalbuminuria: a 3-year follow-up study. Horm Metab Res 47:138–144

    CAS  PubMed  Google Scholar 

  • Sorensen CM, Braunstein TH, Holstein-Rathlou NH, Salomonsson M (2012) Role of vascular potassium channels in the regulation of renal hemodynamics. Am J Physiol Renal Physiol 302:F505–F518

    Article  CAS  PubMed  Google Scholar 

  • Stitham J, Hwa J (2016) Prostacyclin, atherothrombosis and diabetes mellitus: physiologic and clinical considerations. Curr Mol Med 16:328–342

    Article  CAS  PubMed  Google Scholar 

  • Taskapan H, Taskapan MC, Orman I, Ulutas O, Yigit A, Ozyalin F, Yologlu S (2013) NGAL and NT-proBNP levels in diabetic patients with macroproteinuria. Ren Fail 35:1273–1277

    Article  CAS  PubMed  Google Scholar 

  • Theilade S, Hansen TW, Goetze JP, Rossing P (2015) Increased plasma concentrations of midregional proatrial natriuretic peptide is associated with risk of cardiorenal dysfunction in type 1 diabetes. Am J Hypertens 28:772–779

    Article  CAS  PubMed  Google Scholar 

  • Troncoso Brindeiro CM, Fallet RW, Lane PH, Carmines PK (2008) Potassium channel contributions to afferent arteriolar tone in normal and diabetic rat kidney. Am J Physiol Renal Physiol 295:F171–F178

    Article  PubMed  PubMed Central  Google Scholar 

  • Troncoso Brindeiro CM, Lane PH, Carmines PK (2012) Tempol prevents altered K+ channel regulation of afferent arteriolar tone in diabetic rat kidney. Hypertension 59:657–664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woodard GE, Rosado JA (2008) Natriuretic peptides in vascular physiology and pathology. Int Rev Cell Mol Biol 268:59–93

    Article  CAS  PubMed  Google Scholar 

  • Vallon V, Thomson SC (2012) Renal function in diabetic disease models: the tubular system in the pathophysiology of the diabetic kidney. Annu Rev Physiol 74:351–375

    Article  CAS  PubMed  Google Scholar 

  • van der Zander K, Houben AJ, Kroon AA, De Mey JG, Smits PA, de Leeuw PW (2002) Nitric oxide and potassium channels are involved in brain natriuretic peptide induced vasodilatation in man. J Hypertens 20:493–499

    Article  PubMed  Google Scholar 

  • Vesely DL, Gower WR Jr, Dietz JR, Overton RM, Clark LC, Antwi EK, Farese RV (1999) Elevated atrial natriuretic peptides and early renal failure in type 2 diabetic Goto-Kakizaki rats. Metabolism 48:771–778

    Article  CAS  PubMed  Google Scholar 

  • Volpe M (2014) Natriuretic peptides and cardio-renal disease. Int J Cardiol 176:630–639

    Article  PubMed  Google Scholar 

  • Zhao LM, Zhang W, Wang LP, Li GR, Deng XL (2012) Advanced glycation end products promote proliferation of cardiac fibroblasts by upregulation of KCa3.1 channels. Pflugers Arch 464:613–621

    Article  CAS  PubMed  Google Scholar 

  • Zhao LM, Su XL, Wang Y, Li GR, Deng XL (2013) KCa3.1 channels mediate the increase of cell migration and proliferation by advanced glycation end products in cultured rat vascular smooth muscle cells. Lab Investig 93:159–167

    Article  CAS  PubMed  Google Scholar 

  • Zhou HL, Fiscus RR (1989) Brain natriuretic peptide (BNP) causes endothelium-independent relaxation and elevation of cyclic GMP in rat thoracic aorta. Neuropeptides 14:161–169

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors are grateful to Salvador Banacloche for his technical assistance.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Unidad Mixta de Investigación Cerebrovascular (UMIC), Departamento de Fisiología, Universidad de Valencia–Instituto de Investigación Sanitaria La Fe, Valencia, Spain

    José M. Centeno, Luis Miranda-Gómez, Mikahela A. López-Morales, Teresa Jover-Mengual, María C. Burguete, Vannina G. Marrachelli, Alicia Aliena-Valero, Enrique Alborch & Francisco J. Miranda

  2. Departamento de Biología Celular, Biología Funcional y Antropología Física, Universidad de Valencia, Valencia, Spain

    María Castelló-Ruiz

  3. Departamento de Fisiología, Facultad de Farmacia, Universidad de Valencia, Avda. Vicent Andrés Estellés s/n, 46100, Burjassot, Valencia, Spain

    Francisco J. Miranda

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  1. José M. Centeno
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  2. Luis Miranda-Gómez
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  3. Mikahela A. López-Morales
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  4. Teresa Jover-Mengual
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  5. María C. Burguete
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  6. Vannina G. Marrachelli
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  7. María Castelló-Ruiz
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  8. Alicia Aliena-Valero
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  9. Enrique Alborch
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  10. Francisco J. Miranda
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Corresponding author

Correspondence to Francisco J. Miranda.

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Ethical approval

Housing conditions and experimental procedures were performed in strict compliance with the European Union (Directive 2010/63/EU) and Spanish (RD 53/2013) regulations on the use of animals for scientific purposes and approved by the Ethics Committee for Animal Experimentation and Welfare from the University of Valencia (ref. A11295344586921).

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The authors declare that they have no conflict of interest.

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Centeno, J.M., Miranda-Gómez, L., López-Morales, M.A. et al. Diabetes modifies the role of prostanoids and potassium channels which regulate the hypereactivity of the rabbit renal artery to BNP. Naunyn-Schmiedeberg's Arch Pharmacol 391, 501–511 (2018). https://doi.org/10.1007/s00210-018-1478-4

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  • DOI: https://doi.org/10.1007/s00210-018-1478-4

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