Role of endogenous ouabain on vascular function and autonomic modulation in DOCA-Salt hypertensive rats

• Grant number: 10/18380-6
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2011
• End date: December 31, 2013
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Luciana Venturini Rossoni
• Grantee: Luciana Venturini Rossoni
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Vagner Roberto Antunes

Abstract

Hypertension is a cardiovascular disease characterized by increased peripheral vascular resistance, in which the resistance arteries and activation of the sympathetic nervous system play an important role. From the 80's, has been shown that hypertension coexists with increased plasma levels of a factor that inhibits the Na+K+-ATPase, both in humans and in experimental animal models (e.g. Doca-salt hypertensive rats), whose identity was revealed as ouabain. Since 1993, several studies have shown that chronic treatment with ouabain induces hypertension in rats, which seems to be associated with increased sympathetic tone and peripheral adjustments in the cardiac, renal and vascular systems. In 1998, Ferrari and colleagues developed a new molecule called rostafuroxin (PST 2238) (17²-(3-furyl)-5²-androstane-3², 14², 17±-triol), which is able to antagonize the ouabain effects by displacing the specific binding of this glycoside with Na+K+-ATPase. Although records has been shown on the mechanisms involved in the genesis and/ or maintenance of hypertension induced by ouabain in rats, questions about the effects of endogenous ouabain on this disease still exist and deserve attention. Thus, it is clearly important to investigate the influence of pharmacological tools to mitigate or even reverse the effects of endogenous ouabain on the hypertensive process and to confirm its real contribution in the genesis and/ or maintenance of hypertension pressure. Accordingly, knowing the central role of the vascular territory and the sympathetic nervous system in blood pressure control, the aim of this project is to evaluate the role of endogenous ouabain by using a drug that inhibit the action of this glycoside on the Na+K+-ATPase, the rostafuroxin, on blood pressure, heart rate, vascular reactivity in mesenteric resistance arteries and splanchnic sympathetic nerve activity in a model of hypertension (DOCA-salt rats). Within this context, it seems reasonable to assume that an antihypertensive, which is able to antagonize the effects of endogenous ouabain may represent a new and specific pharmacological tool for the treatment of hypertension. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ANDROWIKI, ALINE C. D.; CAMARGO, LIVIA DE LUCCA; SARTORETTO, SIMONE; COUTO, GISELE K.; RIBEIRO, IZABELA M. R.; VERISSIMO-FILHO, SIDNEY; ROSSONI, LUCIANA V.; LOPES, LUCIA R.. Protein disulfide isomerase expression increases in resistance arteries during hypertension development. Effects on Nox1 NADPH oxidase signaling. FRONTIERS IN CHEMISTRY, v. 3, MAR 27 2015. (13/07937-8, 13/03520-5, 10/18380-6)

DE OLIVEIRA, HELANE TITO; COUTO, GISELE KRUGER; DAVEL, ANA PAULA; XAVIER, FABIANO ELIAS; ROSSONI, LUCIANA VENTURINI. Chronic cyclooxygenase-2 inhibition prevents the worsening of hypertension and endothelial dysfunction induced by ouabain in resistance arteries of spontaneously hypertensive rats. VASCULAR PHARMACOLOGY, v. 139, AUG 2021. (10/18380-6)

WENCESLAU, CAMILLA F.; ROSSONI, LUCIANA V.. Rostafuroxin ameliorates endothelial dysfunction and oxidative stress in resistance arteries from deoxycorticosterone acetate-salt hypertensive rats: the role of Na+K+-ATPase/cSRC pathway. Journal of Hypertension, v. 32, n. 3, p. 542-554, MAR 2014. (10/18380-6)

DE FRANCA-NETO, ALDAIR; COUTO, GISELE KRUGER; XAVIER, FABIANO ELIAS; ROSSONI, LUCIANA VENTURINI. Cyclooxygenase-2 is a critical determinant of angiotensin II-induced vascular remodeling and stiffness in resistance arteries of ouabain-treated rats. Journal of Hypertension, v. 40, n. 11, p. 12-pg., 2022-11-01. (10/50048-1, 12/00217-7, 10/18380-6)

ANDROWIKI, ALINE C. D.; CAMARGO, LIVIA DE LUCCA; SARTORETTO, SIMONE; COUTO, GISELE K.; RIBEIRO, IZABELA M. R.; VERISSIMO-FILHO, SIDNEY; ROSSONI, LUCIANA V.; LOPES, LUCIA R.. Protein disulfide isomerase expression increases in resistance arteries during hypertension development. Effects on Nox1 NADPH oxidase signaling. RONTIERS IN CHEMISTR, v. 3, p. 10-pg., 2015-03-27. (13/07937-8, 10/18380-6, 13/03520-5)