The Expressions of Sodium Chloride Cotransporter (NCC mRNAs) in the Kidney Hypertensive Rats

The present study hypothesized that chronic administration of candesartan will not only improve the sensitivity of alpha-adrenergic receptors to adrenergic agonists but also modulate the expression of angiotensin receptors (AT1a) and sodium chloride cotransporter (NCC) mRNAs. Animals were divided into four groups WKY control; WKY received candesartan (WKY-CST, 10 mg/kg), SHR control, and SHR received candesartan (SHR-CST). Plasma, urine samples, and mean arterial pressure (MAP) were taken on days 0, 21, and 28. Acute studies determined the renal vasoconstrictor actions of Ang II, noradrenaline (NA), phenylephrine (PE), and methoxamine (ME). The overall mean drops in renal cortical blood perfusion (RCBP) to NA, PE, ME, and Ang II were significantly increased in WKY-CST and SHR-CST when compared to the respective control. Expression of AT1a mRNA in the kidney of WKY-CST and SHR-CST were increased 11 folds and 8 folds respectively when compared to internal control (β-actin). Expression of NCC MRNA in the kidney of WKY-CST and SHR-CST were 10 folds and 6 folds respectively when compared to internal control. Candesartan restores the functional responsiveness of alpha-adrenergic receptors in normal and spontaneously hypertensive rats by alleviating mean arterial pressure, enhancing renal cortical blood perfusion, and increasing the functional capabilities of the kidney by modulating renal tubular and glomerular functions. Secondly, chronic administrations of candesartan in SHR regulated the expression of AT1a mRNA and NCC mRNA in SHR rat kidneys when compared to SHR control rats.

1.        Wolf-Maier K, Cooper RS, Banegas JR, Giampaoli S, Hense HW, Joffres M, et al. HYpertension prevalence and blood pressure levels in 6 european countries, canada, and the united states. JAMA. 2003;289(18):2363-9.

2.        Nasr AMA, Ahmed YAM, Gafar AAM, Ahmed SAD, Barri BKA, TalibMeshref E, et al. Prevalence and Risk Factors of Choriocarcinoma in Saudi Arabia: A Systematic Review. Clin Cancer Investig J. 2022;11(6):4-8.

3.        Chen L, Shuai J, Liu T. Germinal Center-Derived Diffuse Large B-cell Lymphomas with Aberrant Co-expression of MUM1 in Adults and Children. Clin Cancer Investig J. 2022;11(5):1-6.

4.        Kotchen TA, Kotchen JM. Regional Variations of Blood Pressure Environment or Genes? Circulation. 1997;96(4):1071-3.

5.        Li L, Yi-Ming W, Li Z-Z, Zhao L, Yu Y-S, Li D-J, et al. Local RAS and inflammatory factors are involved in cardiovascular hypertrophy in spontaneously hypertensive rats. Pharmacol Res. 2008;58(3):196-201.

6.        Panigrahi C, Yuwanati M, Senthil MM, Priyadharshini R. Determination of Intracellular Iron in Oral Squamous Cell Carcinoma Using Perl’s Prussian Blue Iron Stain. Clin Cancer Investig J. 2022;11(5):7-10.

7.        Shekatkar M, Kheur S, Deshpande S, Sakhare S, Kumbhar G, Kheur M, et al. Estimation of Salivary Magnesium Levels in Patients with Oral Squamous Cell Carcinoma. Clin Cancer Investig J. 2022;11(3):30-4.

8.        Sharma S, Magar PT, Achhami S, Hamal P, Chapagain B, Jaiswal S, et al. Bacterial profiling and antibiotic-resistant pattern among cancer patients. Clin Cancer Investig J. 2022;11(2):14-20.

9.        Nguyen TPL, Nguyen TT, Nguyen TD, Nguyen TVH. Psychological Empowerment and Employee Creativity in Vietnam Telecommunication Enterprises: The Mediating Role of Intrinsic Work Motivation. J Organ Behav Res. 2022;7(2):132-42.

10.      Elgendy TYAAA. Proposed Model for Selection of the Internal Auditor Using Analytical Network Process: Case Study. J Organ Behav Res. 2022;7(1):138-55.

11.      Maralov VG, Sitarov VA, Koryagina II, Kudaka MA, Smirnova OV, Romanyuk LV. The Relationship of Neuropsychological and Personal Factors with The Attitude to Dangers Among Students. J Organ Behav Res. 2022;7(1):108-24.

12.      Suzuki J, Matsubara H, Urakami M, Inada M. Rat angiotensin II (type 1A) receptor mRNA regulation and subtype expression in myocardial growth and hypertrophy. Circ Res. 1993;73(3):439-47.

13.      Stegbauer J, Gurley SB, Sparks MA, Woznowski M, Kohan DE, Yan M, et al. AT1 receptors in the collecting duct directly modulate the concentration of urine. J Am Soc Nephrol. 2011;22(12):2237-46.

14.      Obata J-e, Nakamura T, Takano H, Naito A, Kimura H, Yoshida Y, et al. Increased gene expression of components of the renin-angiotensin system in glomeruli of genetically hypertensive rats. J Hypertens. 2000;18(9):1247-55.

15.      Naito Y, Tsujino T, Fujioka Y, Ohyanagi M, Iwasaki T. Augmented diurnal variations of the cardiac renin-angiotensin system in hypertensive rats. Hypertension. 2002;40(6):827-33.

16.      Brooks HL, Allred AJ, Beutler KT, Coffman TM, Knepper MA. Targeted proteomic profiling of renal Na+ transporter and channel abundances in angiotensin II type 1a receptor knockout mice. Hypertension. 2002;39(2):470-3.

17.      Vallon V, Schroth J, Lang F, Kuhl D, Uchida S. Expression and phosphorylation of the Na+Cl- cotransporter NCC in vivo is regulated by dietary salt, potassium, and SGK1. Am J Physiol-Renal Physiol. 2009;297(3):F704-F12.

18.      Gamba G, Miyanoshita A, Lombardi M, Lytton J, Lee WS, Hediger MA, et al. Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney. J Biol Chem. 1994;269(26):17713-22.

19.      Eladari D, Chambrey R, Peti-Peterdi J. A new look at electrolyte transport in the distal tubule. Ann Rev Physiol. 2012;74:325-49.

20.      Yang LE, Leong PKK, McDonough AA. Reducing blood pressure in SHR with enalapril provokes redistribution of NHE3, NaPi2, and NCC and decreases NaPi2 and ACE abundance. Am J Physiol-Renal Physiol. 2007;293(4):F1197-F208.

21.      Fanestil DD, Vaughn DA, Hyde RH, Blakely P. Genetic control of renal thiazide receptor response to dietary NaCl and hypertension. Am J Physiol-Regul Integr Comp Physiol. 1999;276(3):R901-R4.

22.      Moreno G, Bobadilla NA, Gonzalez-Salazar J, Mercado A, Tapia E, Hong E, et al. Thiazide-sensitive cotransporter mRNA expression is not altered in three models of hypertension. Kidney Blood Press Res. 2001;24(1):57-63.

23.      Beutler KT, Masilamani S, Turban S, Nielsen J, Brooks HL, Ageloff S, et al. Long-term regulation of ENaC expression in kidney by angiotensin II. Hypertension. 2003;41(5):1143-50.

24.      Alaghemandan H, Ferdosi M, Savabi O, Yarmohammadian MH. Proposing a Framework for Accreditation of Dental Clinics in Iran. J Organ Behav Res. 2022;7(2):161-70.

25.      Ayboğa MH, Ganii F. The Covid 19 Crisis and The Future of Bitcoin in E-Commerce. J Organ Behav Res. 2022;7(2):203-13.

26.      Hye Khan MA, Abdul Sattar M, Abdullah NA, Johns EJ. Cisplatin-induced nephrotoxicity causes altered renal hemodynamics in Wistar Kyoto and spontaneously hypertensive rats: Role of augmented renal alpha-adrenergic responsiveness. Exp Toxicol Pathol. 2007;59(3):253-60.

27.      Abdulla MH, Sattar MA, Abdullah NA, Khan MAH, Anand Swarup KRL, Johns EJ. The contribution of α1B-adrenoceptor subtype in the renal vasculature of fructose-fed Sprague–Dawley rats. Eur J Nutr. 2011;50(4):251-60.

28.      Abdulla MH, Sattar MA, Abdullah NA, Khan AH, Anand Swarup KRL, Rathore HA, et al. Effect of renal sympathetic nerve on adrenergically and angiotensin II-induced renal vasoconstriction in normal Wistar-Kyoto rats. Ups J Med Sci. 2011;116(1):18-25.

29.      Ahmad A, Sattar MA, Rathore HA, Abdulla MH, Khan SA, Azam M, et al. Up Regulation of cystathione γ lyase and Hydrogen Sulphide in the Myocardium Inhibits the Progression of Isoproterenol–Caffeine Induced Left Ventricular Hypertrophy in Wistar Kyoto Rats. PLOS ONE. 2016;11(3):e0150137.

30.      Ahmad A, Sattar M, Rathore HA, Akhtar S, Khan MA, Hashmi F, et al. Impact of isoprenaline and caffeine on development of left ventricular hypertrophy and renal hemodynamic in wistar kyoto rats. Measurements. 2012;76(364).

31.      Ahmad A, Sattar MA, Azam M, Khan SA, Bhatt O, Johns EJ. Interaction between nitric oxide and renal α1-adrenoreceptors mediated vasoconstriction in rats with left ventricular hypertrophyin Wistar Kyoto rats. PloS one. 2018;13(2):e0189386.

32.      Abdulla MH, Sattar MA, Johns EJ, Abdullah NA, Abdul Hye Khan M, Rathore HA. High-fructose feeding impacts on the adrenergic control of renal haemodynamics in the rat. Br J Nutr. 2012;107(2):218-28.

33.      Shawky M, Aljahdali E, Alkhanbashi R. Medication-Related Osteonecrosis of the Jaw: Evaluation of Knowledge and Attitude Among Saudi Dental Students and Interns. Ann Dent Spec. 2022;10(2):52-9.

34.      Mohandas R, Ramani P, Mohapatra S. Corono-Condylar Distance: A Novel Indicator of Chronological Age – A Digital Radiographic Study. Ann Dent Spec. 2022;10(2):73-5.

35.      Verma P, Pandian SM. Prevalence of Endodontically Treated Posteriors in Patients Undergoing Orthodontic Treatment- Cross-Sectional Radiographic Evaluation. Ann Dent Spec. 2022;10(1):1-6.

36.      Zahid TM, Khan NS. Myrrh and Chlorhexidine Mouthwashes Comparison for Plaque, Gingivitis and Inflammation Reduction: A 3-Arm Randomized Controlled Trial. Ann Dent Spec. 2022;10(1):39-46.

37.      Alhussain BS, Alamri FS, Alshehri FA, Aloraini AA, Alghamdi SM, Alfuhaid NA, et al. Mechanical Properties, Occlusal Fit and Success of CAD/CAM Designed Ceramic Endocrowns: A Systematic Review. Ann Dent Spec. 2021;9(4):28-33.

38.      Abdulla MH, Sattar MA, Khan MAH, Abdullah NA, Johns EJ. Influence of sympathetic and AT1-receptor blockade on angiotensin II and adrenergic agonist-induced renal vasoconstrictions in spontaneously hypertensive rats. Acta Physiologica. 2009;195(3):397-404.

39.      Abdulla MH, Sattar MA, Abdullah NA, Khan MAH, Swarup KRA, Johns EJ. The contribution of α1B-adrenoceptor subtype in the renal vasculature of fructose-fed Sprague–Dawley rats. Eur J Nutr. 2011;50(4):251-60.

40.      Ahmad A, Sattar MA, Rathore HA, Abdulla MH, Khan SA, Abdullah NA, et al. Functional contribution of α1D-adrenoceptors in the renal vasculature of left ventricular hypertrophy induced with isoprenaline and caffeine in Wistar–Kyoto rats. Can J Physiol Pharmacol. 2014;92(12):1029-35.

41.      Ahmad FU, Sattar MA, Rathore HA, Abdullah MH, Tan S, Abdullah NA, et al. Exogenous hydrogen sulfide (H2S) reduces blood pressure and prevents the progression of diabetic nephropathy in spontaneously hypertensive rats. Ren Fail. 2012;34(2):203-10.

42.      Abdulla MH SM, Abdullah NA, Khan MA, Abdallah HH, Johns EJ. Chronic treatment with losartan and carvedilol differentially modulates renal vascular responses to sympathomimetics compared to treatment with individual agents in normal Wistar Kyoto and spontaneously hypertensive rats. Eur J Pharmacol. 2009;612(1-3):69-74.

43.      Sattar MA, Johns EJ. [alpha]1-Adrenoceptor Subtypes Mediating Adrenergic Vasoconstriction in Kidney of Two Kidney, One-Clip Goldblatt and Deoxycorticosterone Acetate-Salt Hypertensive Rats. J Cardiovasc Pharmacol. 1994;24(3):420-8.

44.      Armenia A, Munavvar AS, Abdullah NA, Helmi A, Johns EJ. The contribution of adrenoceptor subtype(s) in the renal vasculature of diabetic spontaneously hypertensive rats. Br J Pharmacol. 2004;142:719-26.

45.      Hye Khan MA, Sattar MA, Abdullah NA, Johns EJ. Cisplatin cause altered renal hemodynamics in rats role of augmented a-adrenergic responsiveness. Exp Toxicol Pathol. 2007;53:253-60.

46.      Hieble JP, Bylund DB, Clarke DE, Eikenburg DC, Langer SZ, Lefkowitz RJ, et al. International Union of Pharmacology. X. Recommendation for nomenclature of alpha 1-adrenoceptors: consensus update. Pharmacol Rev. 1995;47(2):267-70.

47.      Dibona GF, Kopp UC. Neural control of renal function. Physiol Rev. 1997;77(1):75-197.

48.      Abdulla M, Sattar M, Abdullah N, Khan MA, Anand Swarup KL, Johns E. The contribution of α1B-adrenoceptor subtype in the renal vasculature of fructose-fed Sprague–Dawley rats. Eur J Nutr. 2011;50(4):251-60.

49.      Khan H, Sattar M, Abdullah N, Johns E. Influence of combined hypertension and renal failure on functional α1‐adrenoceptor subtypes in the rat kidney. Br J Pharmacol. 2008;153(6):1232-41.

50.      Bidani AK, Griffin KA. Pathophysiology of hypertensive renal damage: implications for therapy. Hypertension. 2004;44(5):595-601.

51.      Kurtz TW. False Claims of Blood Pressure–Independent Protection by Blockade of the Renin Angiotensin Aldosterone System? Am Heart Assoc. 2003;41(2):193-6.

52.      Pépin MN, Bouchard J, Legault L, Éthier J. Diagnostic Performance of Fractional Excretion of Urea and Fractional Excretion of Sodium in the Evaluations of Patients with Acute Kidney Injury with or Without Diuretic Treatment. Am J Kidney Dis. 2007;50(4):566-73.

53.      Yu C, Gong R, Rifai A, Tolbert EM, Dworkin LD. Long-term, high-dosage candesartan suppresses inflammation and injury in chronic kidney disease: nonhemodynamic renal protection. J Am Soc Nephrol. 2007;18(3):750-9.

54.      Bagga A, Bajpai A, Menon S. Approach to renal tubular disorders. Indian J Pediatr. 2005;72:771-6.

55.      Gowda S, Desai PB, Kulkarni SS, Hull VV, Math AA, Vernekar SN. Markers of renal function tests. N Am J Med Sci. 2010;2(4):170-3.

56.      Coresh J, Toto RD, Kirk KA, Whelton PK, Massry S, Jones C, et al. Creatinine clearance as a measure of GFR in screenees for the African-American Study of Kidney Disease and Hypertension pilot study. Am J Kidney dis. 1998;32(1):32-42.

57.      Maciel AT, Investigators IRGo. Back to basics: is there a good reason to not systematically measure urine creatinine in acute kidney injury monitoring? Nephron. 2016;133(2):111-5.

58.      Nautiyal M, Shaltout HA, Chappell MC, Diz DI. Comparison of candesartan and angiotensin-(1–7) combination to mito-tempo treatment for normalizing blood pressure and sympathovagal balance in (mren2) 27 rats. J Cardiovasc Pharmacol. 2019;73(3):143.

59.      Xu L, Hu G, Qiu J, Fan Y, Ma Y, Miura T, et al. High Fructose‐Induced Hypertension and Renal Damage Are Exaggerated in Dahl Salt‐Sensitive Rats via Renal Renin‐Angiotensin System Activation. J Am Heart Assoc. 2021;10(14):e016543.

60.      Gowrisankar YV, Clark MA. Angiotensin II regulation of angiotensin-converting enzymes in spontaneously hypertensive rat primary astrocyte cultures. J Neurochem. 2016;138(1):74-85.

61.      Mollnau H, Wendt M, Szöcs K, Lassègue B, Schulz E, Oelze M, et al. Effects of angiotensin II infusion on the expression and function of NAD(P)H oxidase and components of nitric oxide/cGMP signaling. Circ Res. 2002;90(4):E58-65.

62.      Ahmad A, Dempsey SK, Daneva Z, Azam M, Li N, Li P-L, et al. Role of nitric oxide in the cardiovascular and renal systems. Int J Mol Sci. 2018;19(9):2605.

63.      Nishimura Y, Ito T, Hoe KL, Saavedra JM. Chronic peripheral administration of the angiotensin II AT1 receptor antagonist candesartan blocks brain AT1 receptors. Brain Res. 2000;871(1):29-38.

64.      Wamsley-Davis A, Padda R, Truong LD, Tsao CC, Zhang P, Sheikh-Hamad D. AT1A-mediated activation of kidney JNK1 and SMAD2 in obstructive uropathy: preservation of kidney tissue mass using candesartan. Am J Physiol-Renal Physiol. 2004;287(3):F474-F80.

65.      Kobayashi R, Nagano M, Nakamura F, Higaki J, Fujioka Y, Ikegami H, et al. Role of angiotensin II in high fructose-induced left ventricular hypertrophy in rats. Hypertension. 1993;21(6 Pt 2):1051-5.

66.      Castañeda-Bueno M, Cervantes-Pérez LG, Vázquez N, Uribe N, Kantesaria S, Morla L, et al. Activation of the renal Na+: Cl− cotransporter by angiotensin II is a WNK4-dependent process. Proc Natl Acad Sci. 2012;109(20):7929-34.