Implications of the interaction between signaling pathways mediated by Ca2+ and cAMP in the regulation of sympathetic activity: advances for antihypertensive drug therapy

• Grant number: 17/11977-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2017
• End date: July 31, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Autonomic Pharmacology
• Principal Investigator: Afonso Caricati Neto
• Grantee: Lucas Teodoro
• Host Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

A recent study from our lab unraveled the mechanisms involved in the cellular process called the "calcium paradox." The study demonstrated that reducing Ca2+ influx through L-type voltage-dependent Ca2+ channel blockers, such as verapamil, combined with drugs that increase cytosolic cAMP concentration, such as rolipram, promoted potentiation of the contractile activity of smooth muscle, rather than inhibition, stimulated by neurotransmitters of sympathetic nerves. Therefore, the "calcium paradox" has its cellular mechanisms linked, mainly, the interaction between the Ca2+ ion and the second cAMP messenger. Several data from our laboratory have shown that spontaneously hypertensive rats (SHR) have increased both cytosolic and mitochondrial concentrations of Ca 2+. Based on what has been described above the present project aims to investigate the interaction between cell signaling pathways mediated by Ca2+ and cAMP in the sympathetic function of hypertensive animals. (AU)