Hypertension has been associated to endothelial dysfunction, vascular smooth muscle reactivity alterations to contractile agents and oxidative stress, present in humans and animal models. Previous studies of our laboratory have shown that 2K-1C hypertensive rats have a decrease in caveolae plasmatic membrane from endothelium and vacular smooth muscle compared to those of vessels from normotensive rats (2K), and an increase in reactive oxigen species. The hypothesis of the present work is that, in the 2K-1C hypertension model, the reactive oxigen species could change the endothelial and vascular smooth muscle cells caveolae structural integrity, leading to a decreased NO biodisponibility by eNOS and an impared transmission of hyperpolarization to smooth muscle cells due to changes in condutance and/or intercellular gap junctions formation. So, the objective of this project is elucidate the intracellular signaling mechanisms involved with responses activated by C-type natriuretic peptide (CNP) related to calcium mobilization, nitric oxide and cGMP production. For these purposes we will use techniques such as flow cytometry, enzyme immunoassay and protein content, vascular reactivity experiments to assess myoendothelial gap junctions participation on the putative transmission of the endothelium derived hyperpolarization to adjacent smooht muscle cells, evaluating the reactive oxigen species production and caveolae involvement in these responses.
News published in Agência FAPESP Newsletter about the scholarship: