Role of beta-1 adrenergic receptor in cardiac adrenergic responsiveness in thyrotoxicosis

• Grant number: 10/09648-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2010
• End date: June 30, 2011
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Miriam Oliveira Ribeiro
• Grantee: Bárbara Miranda Leite da Costa Bocco
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Presbiteriana Mackenzie (UPM). Instituto Presbiteriano Mackenzie. São Paulo , SP, Brazil

Abstract

Thyroid hormone has an important role in the regulation of cardiovascular functions. In patients with thyrotoxicosis alterations in cardiac function are observed, such as tachycardia and atrial fibrillation, similar to those observed in state of hyper-stimulation of the Sympathetic System. However, levels of circulating catecholamine are normal or even lower, suggesting that the T3 increases adrenergic responsiveness in the heart. Although several previous studies have evaluated this hypothesis, the results aren't conclusive. The construction of a mouse model with disruption of the protein that encode the ²1 adrenergic receptor, the main isoform that mediates the inotropic and chronotropic effects of Sympathetic System in the heart, allowed a better evaluation of the effect of excess T3 on the cardiac adrenergic responsiveness. Thus we will study animals with knockout for ²1 adrenergic receptor (²1-/-) with thyrotoxicosis induced by daily injections of T3 (30ng/g P.C) and will determine cardiovascular alteration such as heart rate and blood pressure. Also, we will quantify mRNA levels of T3 responsive cardiac genes.