Comparative study of the effects of monotherapy with valsartan versus the associations valsartan/hydrochlorothiazide and valsartan/sacubitril on hemodynamic parameters and cardiac contractility in hypertensive rats.

• Grant number: 23/13561-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Hugo Celso Dutra de Souza
• Grantee: Alana Marcela Azarias Severino
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Introduction: Systemic arterial hypertension (SAH) is a highly prevalent disease in the adult population. Functional cardiac impairments are frequent, and if not contained, they can result in heart failure and favoring a poor prognosis. The search for more efficient pharmacological therapy has been constant. In this regard, monotherapy with AT1 receptor blockers, such as valsartan, as well as its association with diuretics, are commonly used in the treatment of SAH. More recently, a new pharmacological combination has been used to treat heart failure, with excellent results, especially concerning ejection fraction. This is the association of valsartan with sacubitril. However, little is known about this pharmacological combination in relation to the treatment of hypertension, especially regarding parameters of ventricular contractility and reactivity of the coronary bed, which are often impaired in the hypertensive heart. Our hypothesis is that this pharmacological combination promotes greater benefits on cardiac function when compared to another widely used pharmacological combination involving valsartan and a diuretic, such as hydrochlorothiazide. Objective: To investigate and compare the effects of the combined pharmacological treatment of valsartan/hydrochlorothiazide versus valsartan/sacubitril on the reactivity of the coronary bed and cardiac contractility. Methods: Spontaneously hypertensive rats (SHR), adult males (N=32), 16 weeks old (180-200g) will be distributed into four groups (N=8) according to the 14-week treatment protocol; vehicle-treated control group (Vehicle Group); group treated with valsartan (30 mg·kg1·d1) (Valsartan Group); group treated with valsartan (30 mg·kg1·d1) associated with hydrochlorothiazide (10 mg·kg1·d1) (Valsartan-Hydrochlorothiazide Group); group treated with valsartan (30 mg·kg1·d1) associated with sacubitril (38 mg·kg1·d1) (Valsartan-Sacubitrile Group). All groups will undergo the following experimental procedures; recording of blood pressure and heart rate using plethysmography to be performed at the 18th, 22nd, 26th, and 30th weeks of life; analysis of coronary bed reactivity and left ventricular contractility in isolated heart by means of increased flow and increasing administration of b-adrenergic agonists, dobutamine (0.5 - 50 nmol) and salbutamol (1 - 100 nmol).