The role of the kidney in the pathophysiology of hypertension and the likelihood that changes in adrenergic response occurs in hypertension is well documented. These experiments are proposed to test the hypothesis that changes in renal adrenergic receptors and/or signal transduction contribute to the pathogenesis of hypertension. The proposed studies are designed to examine: 1) properties and distribution of renal alpha- adrenergic receptor subtypes by radioligand binding methods, 2) localization of these receptor subtypes by autoradiography, 3) signal transduction of these receptor subtypes by focusing on G-protein linkage, phosphoinositide hydrolysis, and regulation of adenylate cyclases, 4) assessment of alpha-adrenergic receptor subtypes and their G-protein mRNA using in situ hybridization, and 5) physiological role of each receptor by evaluating renal function studies. These methodologies will be used to assess changes in adrenergic receptor subtypes and signal transduction during the prehypertensive (4 weeks) and early hypertensive stages (6-8 weeks) in spontaneously hypertensive rats (SHR). The proposed studies should provide a greater understanding of renal alpha-adrenergic receptors and possible mechanisms regulating these receptors in normotensive and hypertensive animals.
| Jackson, C A; Insel, P A (1993) Renal alpha-adrenergic receptors and genetic hypertension. Pediatr Nephrol 7:853-8 |
