PhD

dissertationThe rennin-angiotensin system is an important component in the regulation of systemic blood pressure. Angiotensin II is the principle effector peptide of this system. Interaction of angiotensin II with specific receptors can produce is several organ systems. When administered into the brain this octa-peptide produces a variety of responses including a stimulation of drinking, increased systemic blood pressure and several neuroendocrine responses. Its effects on the kidney include alterations in arteriolar resistance, mesangial cell contraction and a feedback inhibition of the release of renin. Since this peptide produces profound effects on homeostasis by an interaction with specific receptors, the quantitative technique of in vitro autoradiography was applied to localize receptor populations for angiotensin II. Specific binding sites for a radiolabeled form angiotensin II were localized in various brain and kidney regions. In the rat brain high densities of angiotensin II receptors were observed in the paraventricular and suprachiasmatic nuclei of the hypothalamus, supraoptic nucleus and the posterior lobe of the pituitary, brain areas in which angiotensin II modifies neuroendocrine functions. In addition, receptor populations were detected in several brainstem cardiovascular regions including the locus coeruleus, nucleus of the solitary tract and the dorsal motor nucleus of the vagus. Binding was also detected in several circumventricular organs including the subfornical organ and the organum vasculosum of the lamina terminalis, regions where angiotensin II is believed to produce a dipsogenic effect. Angiotensin II receptors were also detected in several brain regions involved in mediating a variety of somatic and visceral sensory functions. In the kidney angiotensin II receptors have been localized to the glomerulus, vasa recta and ureter. Additional sites were also detected outside the vasa recta in the renal medulla. These localization indicate regions of the kidney involved in angiotensin II receptor mediated alterations in kidney functions. These result supply addition support for many of the postulated roles for angiotensin II in homeostasis by specific actions in the brain and kidney. Additionally, several new potential actions of the renin-angiotensin system in modulating central nervous system sensory input have been indicated