Sodium-glucose cotransporter 2 inhibition does not improve the acute pressure natriuresis response in rats with type 1 diabetes.
SLGT2
blood pressure
diabetes
pressure natriuresis
sodium balance
Journal
Experimental physiology
ISSN: 1469-445X
Titre abrégé: Exp Physiol
Pays: England
ID NLM: 9002940
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
received:
26
09
2022
accepted:
19
12
2022
pubmed:
17
1
2023
medline:
3
3
2023
entrez:
16
1
2023
Statut:
ppublish
Résumé
What is the central question of this study? Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular risk in patients with both diabetic and non-diabetic kidney disease: can SGLT2 inhibition improve renal pressure natriuresis (PN), an important mechanism for long-term blood pressure control, which is impaired in type 1 diabetes mellitus (T1DM)? What is the main finding and its importance? The SGLT2 inhibitor dapagliflozin did not enhance the acute in vivo PN response in either healthy or T1DM Sprague-Dawley rats. The data suggest that the mechanism underpinning the clinical benefits of SGLT2 inhibitors on health is unlikely to be due to an enhanced natriuretic response to increased blood pressure. Type 1 diabetes mellitus (T1DM) leads to serious complications including premature cardiovascular and kidney disease. Hypertension contributes importantly to these adverse outcomes. The renal pressure natriuresis (PN) response, a key regulator of blood pressure (BP), is impaired in rats with T1DM as tubular sodium reabsorption fails to down-regulate with increasing BP. We hypothesised that sodium-glucose cotransporter 2 (SGLT2) inhibitors, which reduce cardiovascular risk in kidney disease, would augment the PN response in T1DM rats. Non-diabetic or T1DM (35-50 mg/kg streptozotocin i.p.) adult male Sprague-Dawley rats were anaesthetised (thiopental 50 mg/kg i.p.) and randomised to receive either dapagliflozin (1 mg/kg i.v.) or vehicle. Baseline sodium excretion was measured and then BP was increased by sequential arterial ligations to induce the PN response. In non-diabetic animals, the natriuretic and diuretic responses to increasing BP were not augmented by dapagliflozin. Dapagliflozin induced glycosuria, but this was not influenced by BP. In T1DM rats the PN response was impaired. Dapagliflozin again increased urinary glucose excretion but did not enhance PN. Inhibition of SGLT2 does not enhance the PN response in rats, either with or without T1DM. SGLT2 makes only a minor contribution to tubular sodium reabsorption and does not contribute to the impaired PN response in T1DM.
Substances chimiques
Blood Glucose
0
dapagliflozin
1ULL0QJ8UC
Glucose
IY9XDZ35W2
Sodium
9NEZ333N27
Sodium-Glucose Transporter 2
0
Sodium-Glucose Transporter 2 Inhibitors
0
Slc5a2 protein, rat
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
480-490Subventions
Organisme : British Heart Foundation
ID : FS/16/54/32730
Pays : United Kingdom
Informations de copyright
© 2022 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.
Références
Abdallah, J. G., Schrier, R. W., Edelstein, C., Jennings, S. D., Wyse, B., & Ellison, D. H. (2001). Loop diuretic infusion increases thiazide-sensitive NA+/Cl-Cotransporter abundance: Role of aldosterone. Journal of the American Society of Nephrology, 12(7), 1335-1341.
Ansary, T. M., Fujisawa, Y., Rahman, A., Nakano, D., Hitomi, H., Kobara, H., Masaki, T., Titze, J. M., Kitada, K., & Nishiyama, A. (2017). Responses of renal hemodynamics and tubular functions to acute sodium-glucose cotransporter 2 inhibitor administration in non-diabetic anesthetized rats /631/443/272/1684 /692/4022/272/1684 article. Scientific Reports, 7(1), 9555.
Bie, P., Wamberg, S., & Kjolby, M. (2004). Volume natriuresis vs. Pressure natriuresis. Acta Physiologica Scandinavica, 181(4), 495-503.
Borges-Júnior, F. A., Silva dos Santos, D., Benetti, A., Polidoro, J. Z., Wisnivesky, A. C. T., Crajoinas, R. O., Antônio, E. L., Jensen, L., Caramelli, B., Malnic, G., Tucci, P. J., & Girardi, A. C. C. (2021). Empagliflozin inhibits proximal tubule NHE3 activity, preserves GFR, and restores euvolemia in nondiabetic rats with induced heart failure. Journal of the American Society of Nephrology, 32(7), 1616-1629.
Chou, C. L., & Marsh, D. J. (1986). Role of proximal convoluted tubule in pressure diuresis in the rat. American Journal of Physiology. Renal Fluid and Electrolyte Physiology, 251(2), F283-F289.
Chou, C. L., & Marsh, D. J. (1988). Time course of proximal tubule response to acute arterial hypertension in the rat. American Journal of Physiology. Renal Fluid and Electrolyte Physiology, 254(4), F601-F607.
Conway, B. R., Rennie, J., Bailey, M. A., Dunbar, D. R., Manning, J. R., Bellamy, C. O., Hughes, J., & Mullins, J. J. (2012). Hyperglycemia and renin-dependent hypertension synergize to model diabetic nephropathy. Journal of the American Society of Nephrology, 23(3), 405-411.
Culshaw, G., Binnie, D., Dhaun, N., Hadoke, P., Bailey, M., & Webb, D. J. (2021). The acute pressure natriuresis response is suppressed by selective ETA receptor blockade. Clinical Science, 136(1), 15-28.
Culshaw, G. J., Costello, H. M., Binnie, D., Stewart, K. R., Czopek, A., Dhaun, N., Hadoke, P. W. F., Webb, D. J., & Bailey, M. A. (2019). Impaired pressure natriuresis and non-dipping blood pressure in rats with early type 1 diabetes mellitus. Journal of Physiology, 597(3), 767-780.
De Ferranti, S. D., De Boer, I. H., Fonseca, V., Fox, C. S., Golden, S. H., Lavie, C. J., Magge, S. N., Marx, N., McGuire, D. K., Orchard, T. J., Zinman, B., & Eckel, R. H. (2014). Type 1 diabetes mellitus and cardiovascular disease: A scientific statement from the American Heart Association and American Diabetes Association. Diabetes Care, 37(10), 2843-2863.
Eickhoff, M. K., Dekkers, C. C. J., Kramers, B. J., Laverman, G. D., Frimodt-Møller, M., Jørgensen, N. R., Faber, J., Danser, A. H. J., Gansevoort, R. T., Rossing, P., Persson, F., & Heerspink, H. J. L. (2019). Effects of dapagliflozin on volume status when added to renin-angiotensin system inhibitors. Journal of Clinical Medicine, 8(6), 779.
Fattah, H., & Vallon, V. (2018). The potential role of SGLT2 inhibitors in the treatment of type 1 diabetes mellitus. Drugs, 78(7), 717-726.
Feldt-Rasmussen, B., Mathiesen, E. R., Deckert, T., Giese, J., Christensen, N. J., Bent-Hansen, L., & Nielsen, M. D. (1987). Central role for sodium in the pathogenesis of blood pressure changes independent of angiotensin, aldosterone and catecholamines in Type 1 (insulin-dependent) diabetes mellitus. Diabetologia, 30(8), 610-617.
Gal, A., Burton, S. E., Weidgraaf, K., Singh, P., Lopez-Villalobos, N., Jacob, A., Malabu, U., & Burchell, R. (2020). The effect of the sodium-glucose cotransporter type-2 inhibitor dapagliflozin on glomerular filtration rate in healthy cats. Domestic Animal Endocrinology, 70, 106376.
Ghezzi, C., Loo, D. D. F., & Wright, E. M. (2018). Physiology of renal glucose handling via SGLT1, SGLT2 and GLUT2. Diabetologia, 61(10), 2087-2097.
Groop, P. H., Dandona, P., Phillip, M., Gillard, P., Edelman, S., Jendle, J., Xu, J., Scheerer, M. F., Thoren, F., Iqbal, N., Repetto, E., & Mathieu, C. (2020). Effect of dapagliflozin as an adjunct to insulin over 52 weeks in individuals with type 1 diabetes: Post-hoc renal analysis of the DEPICT randomised controlled trials. The Lancet Diabetes and Endocrinology, 8(10), 845-854.
Guyton, A. C. (1987). Renal function curve-A key to understanding the pathogenesis of hypertension. Hypertension, 10(1), 1-6.
Guyton, A. C., Coleman, T. G., & Granger, H. J. (1972). Circulation: Overall regulation. Annual Review of Physiology, 34(1), 13-44.
Hilliard, L. M., Nematbakhsh, M., Kett, M. M., Teichman, E., Sampson, A. K., Widdop, R. E., Evans, R. G., & Denton, K. M. (2011). Gender differences in pressure-natriuresis and renal autoregulation: Role of the angiotensin type 2 receptor. Hypertension, 57(2), 275-282.
Ivy, J. R., & Bailey, M. A. (2014). Pressure natriuresis and the renal control of arterial blood pressure. Journal of Physiology, 592(18), 3955-3967.
Jaikumkao, K., Pongchaidecha, A., Chueakula, N., Thongnak, L. O., Wanchai, K., Chatsudthipong, V., Chattipakorn, N., & Lungkaphin, A. (2018). Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, slows the progression of renal complications through the suppression of renal inflammation, endoplasmic reticulum stress and apoptosis in prediabetic rats. Diabetes, Obesity and Metabolism, 20(11), 2617-2626.
Kaissling, B., Bachmann, S., & Kriz, W. (1985). Structural adaptation of the distal convoluted tubule to prolonged furosemide treatment. American Journal of Physiology. Renal Fluid and Electrolyte Physiology, 248(3), F374-F381.
Kinaan, M., Yau, H., Martinez, S. Q., & Kar, P. (2017). Concepts in diabetic nephropathy: From pathophysiology to treatment. Journal of Renal and Hepatic Disorders, 1(2), 10-24.
Lee, Y. B., Han, K., Kim, B., Lee, S. E., Jun, J. E., Ahn, J., Kim, G., Jin, S. M., & Kim, J. H. (2019). Risk of early mortality and cardiovascular disease in type 1 diabetes: A comparison with type 2 diabetes, a nationwide study. Cardiovascular Diabetology, 18(1), 157.
Livingstone, S. J., Levin, D., Looker, H. C., Lindsay, R. S., Wild, S. H., Joss, N., Leese, G., Leslie, P., McCrimmon, R. J., Metcalfe, W., McKnight, J. A., Morris, A. D., Pearson, D. W. M., Petrie, J. R., Philip, S., Sattar, N. A., Traynor, J. P., & Colhoun, H. M. (2015). Estimated life expectancy in a scottish cohort with type 1 diabetes, 2008-2010. Journal of the American Medical Association, 313(1), 37-44.
Lu, Y., Griffen, S. C., Boulton, D. W., & Leil, T. A. (2014). Use of systems pharmacology modeling to elucidate the operating characteristics of SGLT1 and SGLT2 in renal glucose reabsorption in humans. Frontiers of Pharmacology, 5(10), 274.
Lurbe, E., Redon, J., Kesani, A., Pascual, J. M., Tacons, J., Alvarez, V., & Batlle, D. (2002). Increase in nocturnal blood pressure and progression to microalbuminuria in type 1 diabetes. New England Journal of Medicine, 347(11), 797-805.
Maahs, D. M., West, N. A., Lawrence, J. M., & Mayer-Davis, E. J. (2010). Epidemiology of type 1 diabetes. Endocrinology and Metabolism Clinics of North America, 39(3), 481-497.
Masuda, T., Muto, S., Fukuda, K., Watanabe, M., Ohara, K., Koepsell, H., Vallon, V., & Nagata, D. (2020). Osmotic diuresis by SGLT2 inhibition stimulates vasopressin-induced water reabsorption to maintain body fluid volume. Physiological Reports, 8(2), e14360.
Nakano, D., & Pollock, D. M. (2009). Contribution of endothelin A receptors in endothelin 1-dependent natriuresis in female rats. Hypertension, 53(2), 324-330.
Neal, B., Perkovic, V., Mahaffey, K. W., de Zeeuw, D., Fulcher, G., Erondu, N., Shaw, W., Law, G., Desai, M., & Matthews, D. R. (2017). Canagliflozin and cardiovascular and renal events in Type 2 diabetes. New England Journal of Medicine, 377(7), 644-657.
O'Hare, J. P., Anderson, J. V., Millar, N. D., Dalton, N., Tymms, D. J., Bloom, S. R., & Corrall, R. J. M. (1989). Hormonal response to blood volume expansion in diabetic subjects with and without autonomic neuropathy. Clinical Endocrinology, 30(5), 571-579.
Oraby, M. A., El-Yamany, M. F., Safar, M. M., Assaf, N., & Ghoneim, H. A. (2019). Dapagliflozin attenuates early markers of diabetic nephropathy in fructose-streptozotocin-induced diabetes in rats. Biomedicine and Pharmacotherapy, 109(1), 910-920.
Perkovic, V., Jardine, M. J., Neal, B., Bompoint, S., Heerspink, H. J. L., Charytan, D. M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., Cannon, C. P., Capuano, G., Chu, P.-L., de Zeeuw, D., Greene, T., Levin, A., Pollock, C., Wheeler, D. C., Yavin, Y., … Mahaffey, K. W. (2019). Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. New England Journal of Medicine, 380(24), 2295-2306.
Rawshani, A., Rawshani, A., Franzén, S., Eliasson, B., Svensson, A. M., Miftaraj, M., McGuire, D. K., Sattar, N., Rosengren, A., & Gudbjörnsdottir, S. (2017). Range of risk factor levels: Control, mortality, and cardiovascular outcomes in type 1 diabetes mellitus. Circulation, 135(16), 1522-1531.
Roland, J. M., O'Hare, J. P., Walters, G., & Corrall, R. J. M. (1986). Sodium retention in response to saline infusion in uncomplicated diabetes mellitus. Diabetes Research, 3(4), 213-215.
Saito, F., & Kimura, G. (1996). Antihypertensive mechanism of diuretics based on pressure-natriuresis relationship. Hypertension, 27(4), 914-918.
Scholtes, R. A., Muskiet, M. H. A., Van Baar, M. J. B., Hesp, A. C., Greasley, P. J., Karlsson, C., Hammarstedt, A., Arya, N., Van Raalte, D. H., & Heerspink, H. J. L. (2021). Natriuretic effect of two weeks of dapagliflozin treatment in patients with type 2 diabetes and preserved kidney function during standardized sodium intake: Results of the dapasalt trial. Diabetes Care, 44(2), 440-447.
Singh, A. K., & Singh, R. (2020). Gender difference in cardiovascular outcomes with SGLT-2 inhibitors and GLP-1 receptor agonist in type 2 diabetes: A systematic review and meta-analysis of cardio-vascular outcome trials. Diabetes and Metabolic Syndrome: Clinical Research and Reviews, 14(3), 181-187.
Song, J., Knepper, M. A., Verbalis, J. G., & Ecelbarger, C. A. (2003). Increased renal ENaC subunit and sodium transporter abundances in streptozotocin-induced type 1 diabetes. American Journal of Physiology. Renal Physiology, 285(6), F1125-F1137.
Stehouwer, C. D. A., & Smulders, Y. M. (2006). Microalbuminuria and risk for cardiovascular disease: Analysis of potential mechanisms. Journal of the American Society of Nephrology, 17(8), 2106-2111.
Tat, V., & Forest, C. P. (2018). The role of SGLT2 inhibitors in managing type 2 diabetes. Journal of the American Academy of Physician Assistants, 31(6), 35-40.
Thomsen, K., & Shirley, D. G. (1997). The validity of lithium clearance as an index of sodium and water delivery from the proximal tubules. Nephron, 77(2), 125-138.
Thomson, S. C., Rieg, T., Miracle, C., Mansoury, H., Whaley, J., Vallon, V., & Singh, P. (2012). Acute and chronic effects of SGLT2 blockade on glomerular and tubular function in the early diabetic rat. American Journal of Physiology. Regulatory Integrative and Comparative Physiology, 302(1), R75-R83.
Thomson, S. C., & Vallon, V. (2021). Effects of SGLT2 inhibitor and dietary nacl on glomerular hemodynamics assessed by micropuncture in diabetic rats. American Journal of Physiology. Renal Physiology, 320(5), F761-F771.
Vallon, V., Huang, D. Y., Deng, A., Richter, K., Blantz, R. C., & Thomson, S. (2002). Salt-sensitivity of proximal reabsorption alters macula densa salt and explains the paradoxical effect of dietary salt on glomerular filtration rate in diabetes mellitus. Journal of the American Society of Nephrology, 13(7), 1865-1871.
Van Paassen, P., De Zeeuw, D., De Jong, P. E., & Navis, G. (2000). Renin inhibition improves pressure natriuresis in essential hypertension. Journal of the American Society of Nephrology, 11(10), 1813-1818.
Wenstedt, E. F. E., Rorije, N. M. G., Olde Engberink, R. H. G., Van Der Molen, K. M., Chahid, Y., Danser, A. H. J., Van Den Born, B. J. H., & Vogt, L. (2020). Effect of high-salt diet on blood pressure and body fluid composition in patients with type 1 diabetes: Randomized controlled intervention trial. BMJ Open Diabetes Research and Care, 8(1), e001039.
Wu, H., Gonzalez Villalobos, R., Yao, X., Reilly, D., Chen, T., Rankin, M., Myshkin, E., Breyer, M. D., & Humphreys, B. D. (2022). Mapping the single-cell transcriptomic response of murine diabetic kidney disease to therapies. Cell Metabolism, 34(7), 1064-1078.e6.
Zanchi, A., Burnier, M., Muller, M. E., Ghajarzadeh-Wurzner, A., Maillard, M., Loncle, N., Milani, B., Dufour, N., Bonny, O., & Pruijm, M. (2020). Acute and chronic effects of SGLT2 inhibitor empagliflozin on renal oxygenation and blood pressure control in nondiabetic normotensive subjects: A randomized, placebo-controlled trial. Journal of the American Heart Association, 9(13), e016173.
Zannad, F., Ferreira, J. P., Pocock, S. J., Anker, S. D., Butler, J., Filippatos, G., Brueckmann, M., Ofstad, A. P., Pfarr, E., Jamal, W., & Packer, M. (2020). SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: A meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. The Lancet, 396(10254), 819-829.