Diabetes mellitus in the human and chemically induced diabetes in the rat are characterized by abnormal regulation of vascular resistance and pressure within the kidney and increased nephron filtration rate. In addition, there is evidence that there is abnormal regulation of certain neurohumoral systems which regulate systemic blood pressure and vascular resistance. The elevated glucose which is characteristic of diabetes mellitus is osmotically active within the extracellular volume which induces shifts of water from the intracellular compartment. To some degree, this osmotic imbalance between the extracellular and intracellular compartment may be compensated in time by the generation of intracellular solutes. The present studies are designed to evaluate and define the quantitative shift in fluid from intracellular to extracellular compartments with hyperglycemia and the corresponding alterations when blood glucose is acutely controlled. In addition, hyperglycemia may influence the distribution of water within the intrarenal spaces and affect renal interstitial hydrostatic pressure both of which will be measured. These alterations secondary to hyperglycemia may in turn contribute to changes in glomerular hemodynamics and alterations in tubular function including elevations in glomerular capiliary hydrostatic pressure. The streptozotocin- induced model of insulin dependent diabetes mellitus in the rat will be studied both in the awake, chronically catheterized animal and during renal micropuncture. Renal micropuncture techniques will permit the evaluation of all determinants of glomerular hemodynamics and tubular functional alterations. The changes in intracellular, extracellular and plasma volume will be evaluated in the early phases and chronic stages of diabetes mellitus in the rat. The specific goal will be to determine whether these alterations in volume distribution correlate with alterations in renal function both within the intrarenal environment and systemically. Other studies will examine the specific role of angiotensin II, the adrenergic nervous system, prostaglandins and tubuloglomerular feedback activity in the alterations in glomerular hemodynamics and tubular function that are observed. These studies assume importance since elevations of glomerular capillary hydrostatic pressure have been proposed to contribute to the progression of renal disease in diabetes mellitus.
