Abstract

Organum vasculosum laminae terminalis (OVLT) is a circumventricular organ located in the midline anterior wall of the third cerebral ventricle immediately dorsal to the optic chiasm. In this dissertation we hypothesize that OVLT neurons are a major contributor to increased sympathetic nerve activity (SNA) elicited in response to acute central hyperosmotic stimulation.

The role of OVLT neurons in central hyperosmolality-evoked sympathoexcitation . To determine the contribution of OVLT neurons in mediating central hyperosmolality-induced sympathoexcitation and elevated arterial blood pressure (ABP), renal SNA (RSNA) and ABP responses to internal carotid artery (ICA) infusion of solutions of graded concentrations of NaCl were tested before and after lesion or inhibition of the OVLT. Hypertonic NaCl infusions via the vascular supply of the forebrain (or ICA) increased RSNA and/or lumbar SNA (LSNA) as well as ABP, and these responses were concentration-dependent. The same volume of isotonic NaCl had no such effects. In both time control and vasopressin 1a receptor (V1a) blockade experiments, responses to hypertonic NaCl infusions were not altered. After electrolytic lesion of the OVLT, RSNA responses to hypertonic NaCl were significantly decreased, but pressor responses were unaltered. Anatomical control lesions placed lateral to the OVLT had no such effect. To exclude a role for axons of passage, OVLT neuronal activation was inhibited by microinjecting the GABAa receptor agonist muscimol after the first series of ICA injections of iso or hypertonic NaCl. Increases of both RSNA and LSNA in response to ICA hypertonic NaCl were significantly attenuated after muscimol microinjection, whereas pressor responses were again unaffected. Vehicle microinjection into the OVLT and muscimol microinjections placed lateral to the OVLT had no effect on either RSNA or LSNA responses. This study indicates that OVLT neurons contribute to hyperosmolality-evoked sympathetic activation.

Induction of Fos-immunoreactivity in PVN-projecting OVLT neurons by central hyperosmolality. To determine the role of PVN-projecting OVLT neurons in responding to ICA hyperosmolality, Fos immunostaining was performed in combination with retrograde tracer methodologies. Fos is an early response gene which is used as a marker for neuronal synaptic activation. To establish infusion parameters capable of eliciting increases in SNA and ABP, RSNA and ABP responses to ICA infusions (0.1 ml/min, 10 min) of isotonic and graded concentration of hypertonic NaCl (1.5 and 3.0 OsM) were recorded in anesthetized rats. ICA isotonic NaCl had no effect. However, ICA hypertonic NaCl increased both RSNA and ABP, and these increases were concentration-dependent. IV NaCl induced a transient reduction of ABP but had no effect on RSNA. Retrograde tracer deposition bilaterally into the PVN labeled neuronal somata in the dorsal cap (DC) and lateral margins (LM) of the OVLT. Using these infusion parameters to induce sympathoexcitation and pressor responses, ICA infusions of hypertonic solutions in conscious rats induced Fos expression in neurons of both DC and LM. Interestingly, neurons located in the LM were maximally recruited at a lower level of hyperosmotic stimulation than neurons in the DC, suggesting that neurons in the LM have lower threshold for hyperosmotic induction of Fos expression. Equal hyperosmotic load of NaCl and mannitol infused through the ICA produced similar patterns of Fos expression. In control experiments, hyperosmotic NaCl given intravenously was without affect on Fos expression. Infusions of graded concentrations of NaCl through the ICA induced graded increase in the number of Fos expressing OVLT neurons with axons projecting to the PVN and this was equally the case in both regions of the OVLT. Combined with finding from studies of ICA infusions in anesthetized rats, results from the current study suggests that PVN-projecting OVLT neurons in the DC and LM may contribute to sympathoexcitatory responses to central hyperosmolality. (Abstract shortened by UMI.)