Neuro-humoral regulation of the cadiovascular system in physiological and physiopathological conditions

Abstract

The experiments proposed in the present project, ranging from in vivo animal recordings of physiologic parameters and morphometric studies to cell culture and biochemical and molecular biology determinations, are designed to explore in depth some aspects of the neurohumoral regulation of the cardiovascular system and represent the natural extension of our previous work in the topic. The main biologic problems under study include: a) the mechanisms underlying the alterations in the reflex regulation of heart rate and arterial blood pressure in models of diabetes and hypertension; b) endothelial mechanisms involved in the formation and degradation of vasoactive peptides under physiologic and pathophysiologic conditions and c) mechanisms of NO production and action in physiologic and pathophysiologic conditions. Some of the experimental approaches involve methodologies such as electroneuronography of baroreceptorafferents and spectral analysis of heart rate and arterial blood pressure, which will be performed in rats with streptozotocin-induced diabetes or with genetic hypertension and in normal mice, are routinely employed in our laboratories. Similarly, the investigation of the roles of peptidases in the formation and metabolism of vasoactive peptides, especially angiotensin II, as well as the exploration of the contribution of nitric oxide to the pregnancy-associated hyporeactivity to vasoconstrictors will employ the perfusion of isolated vascular beds and myography of isolated arterial segments together with biochemical determinations already in use in our laboratories. Other experimental approaches, such as endothelial cell culture and myographic studies of pressurized resistance vessels, which will allow us to explore the regulation of the expression and release of peptidases, especially elastase-2, as well as the regulation of nitric oxide production will require the implementation of new techniques. (AU)