A insuficiência cardíaca (IC) é uma síndrome que cursa com sintomas como intolerância ao exercício e sinais como o edema periférico (EP). Prejuízo na constrição miogênica (CM) acarreta em aumento da pressão hidrostática capilar e EP. Sabendo dos efeitos benéficos do treinamento físico (TF) sobre o sistema cardiovascular na IC, hipotetizou-se que o TF aeróbio é eficaz em restaurar o prejuízo na CM em artérias tibiais caudais (ATC) e o EP induzido pela IC. A IC induziu aumento no volume da pata o qual foi revertido pelo TF. A CM em ATC foi atenuada nos ICs, e o TF restaurou a mesma por vias como ROCK e razão SERCA-2/Fosfolambano, aumentando à cinética e a sensibilidade ao Ca2+. O TF restaurou o aumento no diâmetro interno (Di) observado nas ATC dos IC. Conclui-se, que as ATCs de ratos com IC apresentam prejuízo da CM e remodelamento eutrófico para fora os quais foram restaurados pelo TF. Os ajustes na CM induzidos pelo TF estão associados a uma melhora na mobilização do Ca2+i e na sensibilização das proteínas contráteis. / Heart failure (HF) is a syndrome with symptoms as exercise intolerance and signs as peripheral edema (PE). Impairment of myogenic constriction (MC) leads to enhancement of capillary hydrostatic pressure and PE. Knowing about the beneficial effects of physical training (PT) on cardiovascular system of HF, we hypothesize that PT is efficient in restore the impaired MC of caudal tibial artery (CTA) and PE induced by HF. HF increases paw volume, which was reversed by PT. The MC of CTA was blunted in HF, and PT restored it by pathway such as ROCK and SERCA-2/Phospholamban ratio, that increases Ca2+ kinetics and sensitization. PT restores the enhanced internal diameter (Di) observed in CTA of HF. Taken together, the CTAs of HF rats present an impairment of MC and eutrophic outward remodelling which are restored by PT. The PT adjustments observed in MC are associated with an improvement in Ca2+ mobilization and contractile protein sensitization.

Calcium sensitization represents a mechanism that enables vascular smooth muscle cells to change the sensitivity of the contractile apparatus to intracellular calcium The aim of this study was to determine to what extent is calcium sensitization modulated by the renin- angiotensin system (RAS), sympathetic nervous system (SNS), nitric oxide (NO) and prostanoids produced by cyclooxygenase (COX). For this purpose we studied the effects of acute and chronic blockade of particular systems on blood pressure changes elicited in conscious normotensive rats by administration of Rho-kinase inhibitor fasudil. Adult male chronically cannulated Wistar rats were used in all experiments. Main findings of this study are as follow: 1) Decrease of blood pressure elicited by Rho-kinase inhibition was enhanced under the conditions of acute NOS inhibition. Inhibition of NOS was shown to have a bigger effect than COX inhibition (this was confirmed under the conditions of acute RAS and SNS inhibition as well). These findings are in agreement with the hypothesis that NO exerts a suppressive effect on calcium sensitization. 2) Chronic NOS inhibition caused hypertension characterized by a more pronounced blood pressure lowering after Rho-kinase inhibition in comparison with control. NO chronically suppresses the calcium...

Vascular resistance is mainly determined by the contraction of vascular smooth muscle (VSM), which is regulated by the phosphorylation of myosin light chain (MLC). VSM contraction is initiated by calcium influx into the VSM cells, which is mediated by transient receptor potential (TRP) channels and L-type voltage- dependent calcium channels (L-VDCC). On the other hand, calcium sensitization is a mechanism enhancing vascular contractile response at a given level of intracellular calcium by RhoA/Rho kinase pathway-mediated inhibition of myosin light chain phosphatase. In this thesis I present the data about i) the role of TRP channels in the mechanisms of vascular smooth muscle contraction, ii) enhanced contractility of arteries from spontaneously hypertensive rats (SHR), and iii) the differences in contraction of arteries from normotensive and hypertensive rats related to the role of RhoA/Rho kinase pathway in three types of experimental hypertension (SHR, Ren-2 transgenic rats and salt-sensitive Dahl rats). In the study concerning TRP channels, I compared the effects of three commonly used non-selective TRP channels inhibitors (2-APB, SKF-96365, FFA) on isolated arteries. Among them 2-APB was the most interesting because the observed inhibitory effects of 2-APB were dependent on the type of...