Effect of the Urotensin-2 Receptor Antagonist - Palosuran on Serum Electrolytes (Na+, K+, Ca++) in Laboratory Rats with Renovascular Hypertension

Kajaia Albina, MD, PhD Gabunia Luiza, MD, PhD, DSc Ghambashidze Ketevan, MD, PhD Ratiani Levan, MD, PhD Pkhaladze Neli, MD, PhD Gogokhia Nino

Abstract


This study was designed to assess the effect of the urotensin-2 receptor antagonist - Palosuran on blood pressure and serum electrolytes in laboratory rats with renovascular hypertension (2 kidneys + 1 clip) and determine possible changes in sodium, potassium, calcium levels.

Studies have shown that Palosuran decreases mean arterial pressure in rats with renovascular hypertension. The vasodilating effect of palosuran exceeds the inhibitory effect of L-NAME on NO and the urotensin-induced endothelium-independent vasoconstrictive effect, especially in the early stages of hypertension. The antihypertensive effect of Palosuran was less manifested in case of relatively late onset of treatment. Supposedly, damaging effects of hypertension on blood vessels increase production of U-II and enhance the endothelium-independent vasoconstrictive effect of urotensin.

The results obtained showed a significant difference between hypertensive and nonhypertensive healthy rats for blood electrolytes. At the early stage of disease modeling Palosuran significantly decreased serum Na+ and increased K+ concentrations in hypertensive rats. Na+ and K+ concentrations were maintained within the normal range even after administration of L-NAME, except during the late-onset of treatment.

In conclusion, Palosuran might represent a new therapeutic option in individuals with hypertension disease at early stages of disease.


Keywords


Urotensin-II Receptors, Renovascular Hypertension, Na+, K+, Ca++, Palosuran

Full Text:

PDF

References


Ames RS, Sarau HM, Chambers JK, Willette RN, Aiyar NV, Romanic AM, et al. Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature. 1999; 40: 282–286;

Douglas SA, Ohlstein EH. Human urotensin-II, the most potent mammalian vasoconstrictor identified to date, as a therapeutic target for the management of cardiovascular disease. Trends Cardiovasc Med. 2000; 10: 229–237;

Cheung, Bernard MY; Leung, Raymond; Man, Yu Bun; Wong, Louisa YF. Plasma concentration of urotensin II is raised in hypertension. Journal of Hypertension: July 2004,v. 22 - Issue 7 pp. 1341-1344;

Douglas SA, Ashton DJ, Sauermelch CF, Coatney RW, Ohlstein DH, Ruffolo MR, et al. Human urotensin‐II is a potent vasoactive peptide: pharmacological characterization in the rat, mouse, dog and primate. J Cardiovasc Pharmacol. 2000; 36: S163–S166;

Douglas SA, Sulpizio AC, Piercy V, Sarau HM, Ames RS, Aiyar NV, et al. Differential vasoconstrictor activity of human urotensin‐II in vascular tissue isolated from the rat, mouse, dog, pig, marmoset and cynomolgus monkey. Br J Pharmacol. 2000; 131: 1262–1274;

Gardiner SM, March JE, Kemp PA, Davenport AP, Bennett T. Depressor and regionally‐selective vasodilator effects of human and rat urotensin II in conscious rats. Br J Pharmacol. 2001; 132: 1625–1629;

Gardiner SM, March JE, Kemp PA et al. Regional heterogeneity in the haemodynamic responses to urotensin II in relation to UT receptor localization. Br J Pharmacol 2006; 147:612-621

Watanabe T, Kanome T, Miyazaki A, Katagiri T. Human urotensin II as a link between hypertension and coronary artery disease. Hypertens Res, 2006; 29: 375–387;

Zhu YC, Zhu YZ, Moore PK. The role of urotensin II in cardiovascular and renal physiology and diseases. Br J Pharmacol 2006; 148: 884–901;

Song W, Abdel‐Razik AE, Lu W, Ao Z, Johns DG, et al. Urotensin II and renal function in the rat. Kidney Int 2006; 69: 1360–1368;

Balment RJ, Song W, Ashton N. Urotensin II: ancient hormone with new functions in vertebrate body fluid regulation. Ann N Y Acad Sci 2005; 1040: 66–73;

Bond H., Winter M.J., Warne J.M. , et al. Plasma concentrations of arginine vasotocin and urotensin II are reduced following transfer of the euryhaline flounder (Platichthys flesus) from seawater to fresh water. Gen Comp Endocrinol, 125 (2002), pp. 113-120;

Douglas S.A., Dhanak D., Johns D.G. From ‘gills to pills’: urotensin-II as a regulator of mammalian cardiorenal function. Trends Pharmacol Sci, 25 (2004), pp. 76-85;

Carotenuto A., Grieco P., Rovero P., et al. Urotensin-II receptor antagonists. Curr Med Chem, 13 (2006), pp. 267-275;

Clozel M. , C. Binkert, M. Birker-Robaczewska, et al. Pharmacology of the urotensin-II receptor antagonist palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt): first demonstration of a pathophysiological role of the urotensin system. J Pharmacol Exp Ther, 311 (2004), pp. 204-212;

Sidharta PN, Wagner FD, Bohnemeier H, Jungnik A, Halabi A, Krahenbuhl S, et al. Pharmacodynamics and pharmacokinetics of the urotensin II receptor antagonist palosuran in macroalbuminuric, diabetic patients. Clin Pharmacol Ther. 2006; 80: 246–256;

Clozel M, Hess P, Qiu C, Ding SS, Rey M. The urotensin‐II receptor antagonist palosuran improves pancreatic and renal function in diabetic rats. J Pharmacol Exp Ther. 2006; 316: 1115–1121;

Kajaia A, Gabunia L, Ghambashidze K., et al. Urotensin-2Receptor Antagonist - Palosuran Decreases Blood Pressure And Plasma Renin Concentration In Laboratory Rats With Renovascular Hypertension. International Journal of Progressive Sciences and Technologies (IJPSAT) ISSN: 2509-0119. 2021, vol. 26, No. 1, pp. 16-24;

Goldblatt P. The Goldblatt experiment: a conceptual paradigm. In: Hypertension: Pathophysiology, Diagnosis and Management, edited by J. H. Laragh and B. M. Brenner. New York: Raven, 1995; pp. 23–35;

Mitchell K., Navar L.. Intrarenal actions of angiotensin II in the pathogenesis of experimental hypertension. In: Hypertension: Pathophysiology, Diagnosis, and Management, edited by J. H. Laragh and B. M. Brenner. New York: Raven, 1995, pp.1437– 1450;

Ploth D. Angiotensin-dependent renal mechanisms in two-kidney one-clip renal vascular hypertension. Am. J. Physiol. 1983. 245 (Renal Fluid Electrolyte Physiol. 14): F131–F141;

Kim, M-H & Choi, M-K Seven dietary minerals (Ca, P, Mg, Fe, Zn, Cu, and Mn) and their relationship with blood pressure and blood lipids in healthy adults with self-selected diet. Biol Trace Elem Res. 2013, 153, 69–75;

Gijsbers, L, Dower, JI, Mensink, M et al. Effects of sodium and potassium supplementation on blood pressure and arterial stiffness: a fully controlled dietary intervention study. J Hum Hypertens. 2015, 29, 592–598;

Tostes R.C.A., Wilde D.W., Bendhack L.M., Webb R.C. Calcium handling by vascular myocytes in hypertension. Braz J Med Biol Res, March, 1997, v. 30(3) 315-323.




DOI: http://dx.doi.org/10.52155/ijpsat.v26.2.3093

Refbacks

  • There are currently no refbacks.


Copyright (c) 2021 Kajaia Albina, MD, PhD Gabunia Luiza, MD, PhD, DSc Ghambashidze Ketevan, MD, PhD Ratiani Levan, MD, PhD Pkhaladze Neli, MD, PhD Gogokhia Nino

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.