The long-term objective of the research is to elucidate the mechanisms which mediate and regulate renal vascular (preglomerular and postglomerular) responses to increase in neural activity. The elucidation of normal control mechanisms will help to identify altered mechanisms in pathological conditions associated with elevated renal nerve activity and loss of kidney function (hypertension). The proposed research will address the following concepts: 1) Increases in renal nerve activity differentially nerve activity , constriction of specific vessels is induced by norepinephrine, alone or in combination with angiotensin II, (3) Different alpha-1 adrenergic receptor subtypes mediate norepinephrine constriction of different renal and (4) Constriction of large arteries versus small arterioles to nerve stimulation is mediated by calcium derived from different sources (extracellular versus intracellular). These concepts will be addressed by observing the in vivo renal microcirculation of the rat hydronephrotic kidney. The diameters of preglomerular vessels, glomerular capsules and capillaries, and efferent arterioles will be measured directly from a calibrated television monitor during direct stimulation of the renal nerve (at varing frequencies or duration) or during reflex-induced increase in renal nerve activity. Stimulation- response curves will be generated for each vascular site to compare relative vessel reactivity. Glomerular hemodynamic changes will be assessed by direct measurements of glomerular capillary pressure (servo- null system)and blood flow (optical doppler RBC velocimeter). To determine the role of norepinephrine to constrict select vessels via specific receptors, stimulation-response curves will repeated after blockade of alpha-la or alpha-1b adrenergic receptors. Similarly, the role of circulating angiotensin II receptor blockade. Shifts in the stimulation responses curves agonist to cause selective constriction. Attenuation of constrictor responses by calcium entry blockers will reflect the dependency of different vessels on influx of extracellular calcium or intracellular calcium release for constriction to nerve stimulation.
| Chen, J; Fleming, J T (1993) Juxtamedullary afferent and efferent arterioles constrict to renal nerve stimulation. Kidney Int 44:684-91 |
| Fleming, J T; Zhang, C; Chen, J et al. (1992) Selective preglomerular constriction to nerve stimulation in rat hydronephrotic kidneys. Am J Physiol 262:F348-53 |
