Elena Mironova, Ph.D.

 I am a research instructor in the Dr. Stockand laboratory at the University of Texas Health San Antonio.  I have an established history of research on the cardiovascular system, ion channels, and epithelial transport as supported by numerous awards, presentations and publications.

In Dr. Stockand’s laboratory, I investigate the involvement of renal sodium channels in regulating blood pressure in an attempt to improve therapy for hypertension and heart disease.  Recently, I helped develop the isolated, split-open tubule preparation in the laboratory.  This tool is instrumental in measuring channel activity in native tissue allowing me to combine such measurements with whole animal studies quantifying systemic water and sodium handling.  This broad-based approach has allowed me to ask novel questions about the cardiovascular system and the role of renal sodium transport in this system that have opened new lines of investigation. In addition, it has enabled me to elucidate the cellular mechanism and understand the consequences of these mechanisms at the level of the whole animal.  For instance, by using this approach, I obtained compelling evidence of an inhibitory paracrine purinergic signaling system that is intrinsic to the distal nephron and necessary for the normal feedback regulation of blood pressure.  As I demonstrated, increases in urine flow evoke ATP release into the urine from intercalated cells.  This ATP activates P2Y2 metabotropic purinergic receptors in principal cells to decrease the activity of ENaC.  A consequence of this is that increases in dietary sodium intake increase renal sodium excretion through this mechanism enabling renal sodium handling to compensate for changes in sodium ingestion.  This is key to normal blood pressure regulation for as I have shown, genetic ablation of the P2Y2 receptor or the conduit for ATP release from intercalated cells increases blood pressure in a sodium-dependent manner. In addition to measuring channel activity in isolated rodent split-open tubule I pioneered similar measurements in native human tissue increasing translational potential of my work.

Recently, I have begun investigating into the role of ADH regulation of ENaC and renal sodium excretion.  The root of this inquiry is based on the counterintuitive observation that ADH increases ENaC activity but yet this increase in ENaC activity seems to facilitate urinary concentration and dilution of plasma rather than the expected increase in plasma sodium as predicted by ENaC being an end-effector of the renin-angiotensin-aldosterone system during control of blood volume and thus, pressure. My near-term goal is to understand the consequences of ADH regulation of ENaC and how this contributes to the regulation of plasma osmolality and volume and consequently blood pressure.