The Role Of The Subfornical Organ In The Control Of Cardiovascular Function And Fluid Homeostasis

Increased circulating levels of angiotensin II (ANG II) are known to act at the subfornical organ (SFO) to produce increases in arterial pressure, drinking and secretion of arginine vasopressin (AVP). These studies were done to investigate whether the SFO projections to the nucleus medianus (NM), supraoptic nucleus (SON) and paraventricular nucleus of the hypothalamus (PVH) mediate these responses.;Experiments done in urethane anesthetized rats showed that the SFO was the most sensitive area in the region for eliciting cardiovascular responses consisting of short and long latency increases in arterial pressure, when electrically stimulated or microinjected with L-glutamate. Ganglionic blockade abolished the short latency pressor response but left long latency responses unaffected.;The functional connections from the SFO to the NM, SON, PVH were further demonstrated by observing that electrical stimulation of the SFO in baroreceptor denervated, urethane anesthetized rats altered cerebral metabolic activity in these structures as measured using tritiated 2-deoxyglucose autoradiography.;An electrophysiological study in urethane anesthetized rats revealed that SFO neurons recorded extracellularly were either antidromically or orthodromically activated by electrical stimulation of the PVH, SON or NM. It was observed that the majority of neurons activated antidromically by either PVH or SON stimulation increased their firing following intracarotid infusion of ANG II and/or hypernatremia.;The functional role of the PVH and NM in mediating the responses to SFO activation was further investigated by testing the effect of electrolytic or kainic acid lesions of the PVH or NM on the responses to activation of the SFO. Lesions of the posterior parvocellular containing portion of the PVH significantly attenuated the cardiovascular responses to electrical stimulation of the SFO in the anesthetized animal and the pressor and drinking response to ANG II microinjected into the SFO in the awake animal. Lesions of the NM dorsal to the anterior commissure attenuated the drinking response only to ANG II microinjected into the SFO.;These results suggest that neurons in the SFO are capable of detecting blood-borne signals of extracellular and intracellular fluid deficits and activating a neural circuit involving the NM, SON and PVH to correct these perturbations