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1

Igbe, Ighodaro, and Osaze Edosuyi. "Mitochondrial Function and Blood Pressure Regulation: From Bioenergetics to Pathophysiology." Tropical Journal of Phytochemistry and Pharmaceutical Sciences 1, no. 1 (September 4, 2022): 2. http://dx.doi.org/10.26538/tjpps/v1i1.2.

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The mitochondrion is the powerhouse of all living cells as it provides the energy needed to maintain obligatory regulatory functions.1 The generation of adenosine triphosphate (ATP) via oxidative phosphorylation underlies the principal role of the mitochondrion in cell survival. Aside this basic contribution to energy generation, the mitochondria has been established to regulate cell death (apoptosis), redox and ion signaling.2 The crosstalk between redox signaling and a myriad of pathological disorders created a nexus between the mitochondrion and the cardiorenal system.3,4 Similarly, the high distribution of mitochondria in organs of the cardiorenal system, meant that these organs such as the kidney, are subject to the effect of mitochondria-induced alterations in redox signaling.5 For instance, mitochondrial dysfunction has been linked to the pathophysiology of kidney disorders.6 Considering the intricate link between the kidneys and blood pressure regulation, mitochondrial dysfunction was suggested to contribute significantly to distortions in renal control of blood pressure. Recently, it was reported that the tricarboxylic acid (TCA) cycle plays a role in the etiology of genetic hypertension.7 This novel iscovery linked the activity of the TCA cycle enzyme, fumarase to a reduction in nitric oxide production and an upregulation in redox signaling in the renal medulla of salt-sensitive rats.7,8 In these animals, an innate mutation in the fumarase enzyme, reduced its activity and increased cellular levels of its substrate, fumarate. Hence, the role of these TCA cycle intermediaries was shifted from being ‘mere’ participants in the generation of energy to endogenous ligands with biochemical targets that alter renal function and by extension, blood pressure. Furthermore, fumarate was shown to reduce blood pressure and modulate the expression of genes that ameliorated hypertension induced renal damage in deoxycorticosterone acetate (DOCA) hypertension, a non-genetic form of hypertension.9 Subsequently, succinate, the upstream product of fumarate was reported to directly stimulate GPR91 receptors to increase blood pressure.10 These actions of fumarate and its intermediaries, exceed the renal system as reports have shown a cardioprotective role via upregulation of nuclear erythroid factor-2 (Nrf2).11 Fumarate is now known to regulate the expression of genes such as hypoxia inducible factor (HIF-1), transforming growth factor (TGF-β), kidney injury molecule (KIM-1) amongst others. What is evident from the foregoing is that the mitochondrion is no longer just an idle energy-generating center. It is now listed as a probable etiology in hypertension, and this has opened new vistas of possibilities as it relates to the pathophysiology of hypertension.8 Is it possible that these intermediaries are involved in the physiological control of blood pressure? Could they also be exerting direct vasoactive effects? Is it likely that they may be modulating the expression of genes that underlie vascular/organ remodeling? And finally, is it possible that mitochondrial dysfunction could partly explain the etiology of idiopathic hypertension? As, far reaching as these insights may be, it is not completely out of place to be optimistic as the foray into these previously uncharted areas of mitochondrial metabolism progress. What is very clear is that there is now a paradigm shift in the function of the mitochondria in blood pressure regulation from that of a bioenergetic center to pathophysiological axis which contributes significantly to the etiology of hypertension.
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2

Jones, John Edward, and Pedro A. Jose. "Neonatal blood pressure regulation." Seminars in Perinatology 28, no. 2 (April 2004): 141–48. http://dx.doi.org/10.1053/j.semperi.2003.11.004.

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3

Lazartigues, Eric D. "Hypothalamic Regulation of Blood Pressure." FASEB Journal 34, S1 (April 2020): 1. http://dx.doi.org/10.1096/fasebj.2020.34.s1.00423.

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4

Dakshinamurti, K., and S. Dakshinamurti. "Blood pressure regulation and micronutrients." Nutrition Research Reviews 14, no. 1 (June 1, 2001): 3–44. http://dx.doi.org/10.1079/095442201108729123.

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5

Luft, F. C., and M. H. Weinberger. "Potassium and blood pressure regulation." American Journal of Clinical Nutrition 45, no. 5 (May 1, 1987): 1289–94. http://dx.doi.org/10.1093/ajcn/45.5.1289.

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6

Kienitz, Tina, and Marcus Quinkler. "Testosterone and Blood Pressure Regulation." Kidney and Blood Pressure Research 31, no. 2 (2008): 71–79. http://dx.doi.org/10.1159/000119417.

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7

Ackermann, U. "Regulation of arterial blood pressure." Surgery (Oxford) 22, no. 5 (May 2004): 120a—120f. http://dx.doi.org/10.1383/surg.22.5.120a.33383.

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8

Mutig, Kerim, and Sebastian Bachmann. "Hyperkalemia and blood pressure regulation." Nephrology Dialysis Transplantation 34, Supplement_3 (December 1, 2019): iii26—iii35. http://dx.doi.org/10.1093/ndt/gfz218.

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Abstract Hypertension is common in the general population. Management of hypertensive patients at risk of hyperkalemia is challenging due to potential life-threatening complications such as cardiac arrest. Chronic hyperkalemia is often associated with impaired renal ability to excrete excessive potassium ions (K+). This may refer to chronic kidney disease or certain pharmacological interventions, including broadly used renin–angiotensin–aldosterone system and calcineurin inhibitors. Understanding the intrinsic mechanisms permitting kidney adaptations to hyperkalemia is critical for choosing therapeutic strategies. Valuable insights were obtained from the analysis of familial hyperkalemic hypertension (FHHt) syndrome, which became a classic model for coincidence of high blood pressure and hyperkalemia. FHHt can be caused by mutations in several genes, all of them resulting in excessive activity of with-no-lysine kinases (WNKs) in the distal nephron of the kidney. WNKs have been increasingly recognized as key signalling enzymes in the regulation of renal sodium ions (Na+) and K+ handling, enabling adaptive responses to systemic shifts of potassium homoeostasis consequent to variations in dietary potassium intake or disease. The WNK signalling pathway recruits a complex protein network mediating catalytic and non-catalytic effects of distinct WNK isoforms on relevant Na+- or K+-transporting proteins. In this review article, we summarize recent progress in understanding WNK signalling. An update of available models for renal adaptation to hyperkalemic conditions is presented. Consequences for blood pressure regulation are discussed. Pharmacological targeting of WNKs or their substrates offers promising options to manage hypertension while preventing hyperkalemia.
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9

Chao, Julie, and Lee Chao. "Kallistatin in Blood Pressure Regulation." Trends in Cardiovascular Medicine 7, no. 8 (November 1997): 307–11. http://dx.doi.org/10.1016/s1050-1738(97)00089-3.

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10

Watts, Stephanie W., Shaun F. Morrison, Robert Patrick Davis, and Susan M. Barman. "Serotonin and Blood Pressure Regulation." Pharmacological Reviews 64, no. 2 (March 8, 2012): 359–88. http://dx.doi.org/10.1124/pr.111.004697.

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11

Jobe, Alan H. "Blood pressure regulation in preterms." Journal of Pediatrics 151, no. 4 (October 2007): A3. http://dx.doi.org/10.1016/j.jpeds.2007.08.028.

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12

Wehrwein, Erica A., Michael J. Joyner, Emma C. J. Hart, B. Gunnar Wallin, Tomas Karlsson, and Nisha Charkoudian. "Blood Pressure Regulation in Humans." Hypertension 55, no. 2 (February 2010): 264–69. http://dx.doi.org/10.1161/hypertensionaha.109.141739.

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13

Feldman, Ross D. "Aldosterone and Blood Pressure Regulation." Hypertension 63, no. 1 (January 2014): 19–21. http://dx.doi.org/10.1161/hypertensionaha.113.01251.

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14

Rowell, Loring B. "Blood Pressure Regulation during Exercise." Annals of Medicine 23, no. 3 (January 1991): 329–33. http://dx.doi.org/10.3109/07853899109148068.

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15

Grünfeld, J. P. "Glucocorticoids in Blood Pressure Regulation." Hormone Research 34, no. 3-4 (1990): 111–13. http://dx.doi.org/10.1159/000181807.

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16

Mannelli, M., C. Pupilli, R. Lanzillotti, L. Ianni, and M. Serio. "Catecholamines and Blood Pressure Regulation." Hormone Research 34, no. 3-4 (1990): 156–60. http://dx.doi.org/10.1159/000181816.

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17

Borghi, Claudio, Maddalena Veronesi, Maria Grazia Prandin, Ada Dormi, and Ettore Ambrosioni. "Statins and blood pressure regulation." Current Hypertension Reports 3, no. 4 (July 2001): 281–88. http://dx.doi.org/10.1007/s11906-001-0090-y.

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18

Tzeng, Yu-Chieh, and Philip N. Ainslie. "Blood pressure regulation IX: cerebral autoregulation under blood pressure challenges." European Journal of Applied Physiology 114, no. 3 (June 5, 2013): 545–59. http://dx.doi.org/10.1007/s00421-013-2667-y.

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19

Pandurangi, Ulhas M. "Neurogenic Factors and Blood Pressure Regulation." Hypertension Journal 2, no. 1 (2016): 35–38. http://dx.doi.org/10.5005/jp-journals-10043-0027.

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20

Fujiiwa, Hideki, and Takeo Masaki. "Blood Pressure Regulation in Preschool Children." Japan Journal of Human Growth and Development Research, no. 26 (1998): 74–79. http://dx.doi.org/10.5332/hatsuhatsu.1998.74.

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21

Jacob, JubbinJagan, Sandeep Chopra, and Chris Baby. "Neuro-endocrine regulation of blood pressure." Indian Journal of Endocrinology and Metabolism 15, no. 8 (2011): 281. http://dx.doi.org/10.4103/2230-8210.86860.

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22

Wu, Cheng-Chia, Tanush Gupta, Victor Garcia, Yan Ding, and Michal L. Schwartzman. "20-HETE and Blood Pressure Regulation." Cardiology in Review 22, no. 1 (2014): 1–12. http://dx.doi.org/10.1097/crd.0b013e3182961659.

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23

Marteau, Jean-Brice, Mohamed Zaiou, Gérard Siest, and Sophie Visvikis-Siest. "Genetic determinants of blood pressure regulation." Journal of Hypertension 23, no. 12 (December 2005): 2127–43. http://dx.doi.org/10.1097/01.hjh.0000186024.12364.2e.

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24

Hall, J. E., T. G. Coleman, H. L. Mizelle, and M. J. Smith. "Chronic hyperinsulinemia and blood pressure regulation." American Journal of Physiology-Renal Physiology 258, no. 3 (March 1, 1990): F722—F731. http://dx.doi.org/10.1152/ajprenal.1990.258.3.f722.

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The aims of this study were to determine whether chronic hyperinsulinemia, comparable to that found in obese hypertensives, elevates mean arterial pressure (MAP) or potentiates the hypertensive effects of angiotensin II (ANG II). Studies were conducted in conscious dogs with kidney mass reduced by 70% in order to increase their susceptibility to hypertensive stimuli. Insulin infusion (0.5 or 1.0 mU.kg-1.min-1 iv) for 7 days with plasma glucose held constant raised plasma insulin more than fivefold but did not increase MAP in four dogs on 138 meq/day Na intake. In seven dogs maintained on a high Na intake (319 meq/day), insulin infusion (1.0 mU.kg-1.min-1) for 28 days raised fasting insulin from 9.8 +/- 1.5 to 56-78 microU/ml but did not increase MAP, which averaged 106 +/- 2 mmHg during control and 102 +/- 2 mmHg during 28 days of insulin infusion. Insulin caused transient sodium and potassium retention followed by renal "escape" that was associated with increased glomerular filtration rate (12-27%). Plasma renin activity and plasma aldosterone were not altered by insulin. In five dogs infused with ANG II (2.0 ng.kg-1.min-1) to cause mild hypertension, insulin infusion (1.0 mU.kg-1.min-1) for 6-28 days did not increase MAP further. Thus chronic hyperinsulinemia did not elevate MAP, even when kidney mass was reduced, and did not potentiate the hypertensive effects of ANG II. These findings suggest that additional factors besides hyperinsulinemia per se are responsible for obesity-associated hypertension.
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25

Reusser, Molly E., and David A. McCarron. "Micronutrient Effects on Blood Pressure Regulation." Nutrition Reviews 52, no. 11 (April 27, 2009): 367–75. http://dx.doi.org/10.1111/j.1753-4887.1994.tb01367.x.

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26

Berkow, Susan E., and Neal D. Barnard. "Blood Pressure Regulation and Vegetarian Diets." Nutrition Reviews 63, no. 1 (January 2005): 1–8. http://dx.doi.org/10.1111/j.1753-4887.2005.tb00104.x.

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27

McCarron, D. A., and M. E. Reusser. "Body weight and blood pressure regulation." American Journal of Clinical Nutrition 63, no. 3 (March 1, 1996): 423S—425S. http://dx.doi.org/10.1093/ajcn/63.3.423.

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28

Campbell, Duncan J. "Extrarenal Renin and Blood Pressure Regulation." American Journal of Hypertension 2, no. 4 (April 1989): 266–75. http://dx.doi.org/10.1093/ajh/2.4.266.

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29

Wazna, Jadwiga, and Yoram Shenker. "Extrarenal Renin and Blood Pressure Regulation." American Journal of Hypertension 5, no. 5_Pt_1 (May 1992): 336–37. http://dx.doi.org/10.1093/ajh/5.5.336.

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30

Johns, Edward J., and Mohammed H. Abdulla. "Renal nerves in blood pressure regulation." Current Opinion in Nephrology and Hypertension 22, no. 5 (September 2013): 504–10. http://dx.doi.org/10.1097/mnh.0b013e3283641a89.

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31

Mettimano, Marco, Maria Lucia Specchia, Giuseppe La Torre, Antonio Bruno, Gualtiero Ricciardi, Luigi Savi, and Vincenzo Romano-Spica. "Blood Pressure Regulation by CCR Genes." Clinical and Experimental Hypertension 28, no. 7 (January 2006): 611–18. http://dx.doi.org/10.1080/10641960600945728.

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32

Ambler, S. Kelly, and R. Dale Brown. "Genetic Determinants of Blood Pressure Regulation." Journal of Cardiovascular Nursing 13, no. 4 (July 1999): 59–77. http://dx.doi.org/10.1097/00005082-199907000-00007.

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33

Ferrara, L. "Serum cholesterol affects blood pressure regulation." American Journal of Hypertension 14, no. 11 (November 2001): A50. http://dx.doi.org/10.1016/s0895-7061(01)02095-7.

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34

Moore, Thomas J., and John A. McKnight. "Dietary Factors and Blood Pressure Regulation." Endocrinology and Metabolism Clinics of North America 24, no. 3 (September 1995): 643–55. http://dx.doi.org/10.1016/s0889-8529(18)30036-7.

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35

Rudolph, Volker, Tanja K. Rudolph, and Bruce A. Freeman. "Blood pressure regulation: role for neutrophils?" Blood 111, no. 10 (May 15, 2008): 4840. http://dx.doi.org/10.1182/blood-2008-03-142513.

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36

Johns, Edward J. "Genes, gender and blood pressure regulation." Journal of Hypertension 21, no. 8 (August 2003): 1447–48. http://dx.doi.org/10.1097/00004872-200308000-00003.

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37

Burke, William J., Pedro G. Coronado, Catherine A. Schmitt, Kathleen M. Gillespie, and Hyung D. Chung. "Blood pressure regulation in alzheimer's disease." Journal of the Autonomic Nervous System 48, no. 1 (June 1994): 65–71. http://dx.doi.org/10.1016/0165-1838(94)90160-0.

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38

Chen, C. Y. "The NTS in blood pressure regulation." Autonomic Neuroscience 192 (November 2015): 18–19. http://dx.doi.org/10.1016/j.autneu.2015.07.305.

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39

Danzi, Sara, and Irwin Klein. "Thyroid hormone and blood pressure regulation." Current Hypertension Reports 5, no. 6 (December 2003): 513–20. http://dx.doi.org/10.1007/s11906-003-0060-7.

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40

Caples, Sean M., and Virend K. Somers. "Sleep, Blood Pressure Regulation, and Hypertension." Sleep Medicine Clinics 2, no. 1 (March 2007): 77–86. http://dx.doi.org/10.1016/j.jsmc.2006.12.005.

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41

Ferrara, L. A., L. Guida, R. Iannuzzi, A. Celentano, and F. Lionello. "Serum cholesterol affects blood pressure regulation." Journal of Human Hypertension 16, no. 5 (May 2002): 337–43. http://dx.doi.org/10.1038/sj.jhh.1001388.

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42

Markel, A. L., and O. E. Redina. "Epigenetic Mechanisms of Blood-Pressure Regulation." Molecular Biology 52, no. 2 (March 2018): 151–64. http://dx.doi.org/10.1134/s0026893317050120.

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43

Ploth, David W. "Monogenic Mechanisms of Blood Pressure Regulation." American Journal of the Medical Sciences 322, no. 6 (December 2001): 301. http://dx.doi.org/10.1097/00000441-200112000-00001.

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44

Isakson, Brant E. "Alpha Hemoglobin in Blood Pressure Regulation." Free Radical Biology and Medicine 128 (November 2018): S1. http://dx.doi.org/10.1016/j.freeradbiomed.2018.10.375.

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45

Castañeda‐Bueno, María, and Gerardo Gamba. "SPAKling insight into blood pressure regulation." EMBO Molecular Medicine 2, no. 2 (February 2010): 39–41. http://dx.doi.org/10.1002/emmm.200900059.

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46

Jhee, Jong Hyun, Hyeong Cheon Park, and Hoon Young Choi. "Skin Sodium and Blood Pressure Regulation." Electrolytes & Blood Pressure 20, no. 1 (2022): 1. http://dx.doi.org/10.5049/ebp.2022.20.1.1.

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47

Hilsted, J. "Blood pressure regulation in diabetic autonomic neuropathy." Clinical Physiology 5, S5 (January 1985): 49–58. http://dx.doi.org/10.1111/j.1365-2281.1985.tb00010.x.

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48

Wall, Susan M. "Renal intercalated cells and blood pressure regulation." Kidney Research and Clinical Practice 36, no. 4 (December 31, 2017): 305–17. http://dx.doi.org/10.23876/j.krcp.2017.36.4.305.

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49

Boscolo, P., and M. Carmignani. "Neurohumoral blood pressure regulation in lead exposure." Environmental Health Perspectives 78 (June 1988): 101–6. http://dx.doi.org/10.1289/ehp.8878101.

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50

Carney, Ellen F. "Regulation of salt appetite and blood pressure." Nature Reviews Nephrology 12, no. 5 (March 21, 2016): 258. http://dx.doi.org/10.1038/nrneph.2016.42.

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