The purpose of this project is to delineate the mechanisms involved in regulating blood flow to juxtamedullary nephrons of the rat kidney. Emphasis is placed on characterization of the ability of the vasculature to maintain blood flow and glomerular filtration rate constant in the face of alterations in perfusion pressure, including evaluation of the role of several mechanisms which may be involved in this autoregulatory response. (Primary candidates include the tubuloglomerular feedback and myogenic mechanisms.) Also, the renal microvascular responses to important vasoactive agents will be evaluated. Experiments will be performed using an in vitro preparation which involves perfusion with homologous blood of juxtamedullary nephrons from the rat kidney. This experimental setting allows visualization of the renal arterial and arteriolar units. Videometric techniques will be utilized to evaluate the blood flow and segmental vascular diameter responses to changes in perfusion pressure or alterations in tubular fluid flow to the distal nephron; micropuncture techniques will be used to measure hydrostatic pressure in the vasculature, collect tubular fluid, and perfuse tubules from proximal tubular sites. Experiments will be performed to characterize the autoregulatory response in vitro, to determine the myogenic capability of the renal vasculature, and to determine the sensitivity of the tubuloglomerular feedback system under these conditions. These experiments will provide the basis for studies designed to evaluate the relative contributions of myogenic and tubuloglomerular feedback mechanisms to the autoregulatory response. In addition, studies will be performed to establish the dependency of autoregulation upon a number of putative modulators of the tubuloglomerular feedback system, and to investigate the influence of suggested autoregulatory mediators on the tubuloglomerular feedback loop. These studies will help delineate the interrelationships between autoregulatory, tubuloglomerular feedback, myogenic, and humoral influences on renal microvascular function.
| Carmines, Pamela K (2014) Mechanisms of renal microvascular dysfunction in type 1 diabetes: potential contribution to end organ damage. Curr Vasc Pharmacol 12:781-7 |
| Carmines, Pamela K (2010) The renal vascular response to diabetes. Curr Opin Nephrol Hypertens 19:85-90 |
