The aim of this proposal is to compare and contrast the structure and function of the glomerular microciculation in two pathogenically distinct experimental models of hypertension and to examine the pathogenesis of renal injury in these settings. This will be accomplished by applying micropuncture and histologic techniques to rats with desoxycorticosterone and saline induced (DOC-SALT) hypertension and genetically determined, spontaneous hypertension (SHR). Four specific experimental protocols are planned. In protocol 1, superficial glomerular hemodynamics will be assessed in uninephrectomized SHR rats. Protocol 2 will determine whether clipping the renal artery to reduce glomerular pressures and flows will protect DOC-SALT rats from renal injury. In separate experiments, the effects of protein restriction on superficial nephron structure and function will be examined in SHR rats post uninephrectomy. Protocol 3 will examine the effects of pharmacologic control of systemic hypertension on glomerular structure and function in both DOC-SALT and SHR rats. Finally, in protocol 4, micropuncture experiments will be performed in DOC-SALT rats to examine the effects on glomerular dynamics of infusions of blockers of several hormones. Hypertension and particularly renal disease associated with hypertension are public health problems of major proportions. Standard modes of therapy which successfully reduce the incidence of stroke and heart disease often fail to halt the progression of hypertensive renal disease. As preliminary experiments indicate that increased glomerular capillary pressures and flows may damage the glomerulus in experimental hypertension, it is now more important than ever to develop a thorough understanding of the renal microcirculatory response to elevations in blood pressure in both treated and untreated populations. This proposal should provide that understanding and therefore might produce data potentially relevant to the treatment of this extremely common disorder.
| Dworkin, L D; Feiner, H D; Parker, M et al. (1990) Calcium carbonate exacerbates glomerular capillary hypertension and injury in rats with desoxycorticosterone-salt hypertension. Am J Hypertens 3:444-50 |
| Dworkin, L D; Grosser, M; Feiner, H D et al. (1989) Renal vascular effects of antihypertensive therapy in uninephrectomized SHR. Kidney Int 35:790-8 |
| Martinez-Maldonado, M; Rodriguez-Sargent, C; Cangiano, J L et al. (1987) Pathogenesis of systemic hypertension and glomerular injury in the spontaneously hypertensive rat. Am J Cardiol 60:47I-52I |
| Dworkin, L D; Feiner, H D; Randazzo, J (1987) Glomerular hypertension and injury in desoxycorticosterone-salt rats on antihypertensive therapy. Kidney Int 31:718-24 |
| Dworkin, L D; Feiner, H D (1986) Glomerular injury in uninephrectomized spontaneously hypertensive rats. A consequence of glomerular capillary hypertension. J Clin Invest 77:797-809 |
