Effect of subfornical organ lesion on the development of mineralocorticoid-salt hypertension.

Accumulating evidence suggests that structures within the lamina terminalis; the organum vasculosm of the lamina terminalis (OVLT), the median preoptic nucleus (MnPO) and/or the subfornical organ (SFO); are required for the development of DOCA-salt hypertension. Lesion of the anteroventral tissue lining the third ventricle (AV3V), which destroys cell bodies in the OVLT and MnPO, as well as efferent projections from the SFO to the OVLT and MnPO, abolishes DOCA-salt hypertension in the rat. However, the individual contribution of these structures to DOCA-salt hypertension is unknown. The present study was designed to determine whether an intact SFO is required for hypertension development in the DOCA-salt model. In uninephrectomized SFO lesioned (SFOx; n=6) and SHAM (n=8) Sprague-Dawley rats, 24-h mean arterial pressure (MAP) and heart rate (HR) were continuously recorded telemetrically 4 days before and 36 days after DOCA implantation (100 mg/rat; s.c.); 24-h sodium and water balances were measured throughout the protocol. No differences in control MAP, HR, sodium and water balances were observed between groups. Following DOCA implantation, the magnitude of the elevation of MAP was similar between groups (approximately 40 mm Hg) so that by Day 40, MAP was 148+/-5 mm Hg in SFOx and 145+/-4 mm Hg in SHAM rats. The magnitude of decrease in HR from control values was similar in both groups. Differences in sodium and water balances were not observed between groups. We conclude that the SFO alone does not play a significant role in the development of mineralocorticoid-salt hypertension.

Forebrain circumventricular organs mediate salt appetite induced by intravenous angiotensin II in rats.

Two circumventricular organs, the subfornical organ (SFO) and organum vasculosum laminae terminalis (OVLT), may mediate salt appetite in response to acute intravenous infusions of angiotensin (ANG) II. Fluid intakes and mean arterial pressures were measured in rats with sham lesions or electrolytic lesions of the SFO or OVLT during an intravenous infusion of 30 ng/min ANG II. Beginning 21 h before the 90-min infusion, the rats were depleted of sodium with furosemide and given a total of 300 mg/kg captopril in 75 ml/kg water in three spaced gavages to block the usual salt appetite and to hydrate the rats. No other food or fluids were available for ingestion. Sham-lesioned rats drank 9.3+/-1.2 ml if 0.3 M NaCl alone was available and drank 8.9+/-1.6 ml of saline and 3.7+/-1.6 ml of water if both were available. Either SFO or OVLT lesions reduced the intakes of saline to <5 ml in both conditions and of water to <1 ml. Mean arterial pressure did not differ among the groups and was maintained above 100 mmHg after the depletion and captopril treatments because of the large doses of water. Thus, a full expression of salt appetite in response to an acute intravenous infusion of ANG II requires the integrity of both the SFO and OVLT.

Respiratory and metabolic effects of decreased osmolality in conscious rats.

We investigated the respiratory and metabolic effects of decreased osmolality, and the potential roles of angiotensin II (ANG II) and the subfornical organ (SFO) in mediating these effects, in conscious Sprague-Dawley (SD) rats. Gastric water loading was induced either by oral gavage or an externalized indwelling stomach tube (20 mL x kg(-1) distilled water at body temperature). Repeated measurements after oral gavage were obtained with and without water loading and with and without ANG II receptor block (saralasin, 1.3 microg x kg(-1) x min(-1) iv). At 15 min after water loading by oral gavage, ventilation (V, 1.14+/-0.08 L x kg(-1) x min(-1)) and tidal volume (10.7+/-0.6 mL x kg(-1)) were transiently higher (P < 0.05), at a time when plasma osmolality was decreased (-8+/-1 mOsm), compared with gavage tube alone (0.95+/-0.08 L x kg(-1) min(-1) and 9.1+/-0.7 mL x kg(-1), respectively). However, water loading via stomach tube did not stimulate V; only during the 60-s period of water infusion did V increase briefly, but this was due to increased respiratory frequency. Dye indicators demonstrated that oral gavage exposes upper airway and esophageal afferents to water, presumably accounting for respiratory stimulation. Lesions of the SFO did not affect respiration or metabolism. A decrease in osmolality, associated with both water loading techniques, caused a sustained increase in oxygen consumption (Vo2 ) and a decrease in the V/Vo2 ratio. ANG II receptor block reduced the Vo2 response and prevented the decrease in V/Vo2 following water loading by oral gavage, but did not affect the transient stimulation of V. Unlike larger mammals, decreased osmolality does not stimulate respiration in the SD rat.

Inhibition of the cortisol response to systemic angiotensin II by forebrain lesions involving the anterior wall of the third ventricle.

The influence of bilaterally narrow, medial forebrain lesions on the increase in plasma cortisol concentration normally seen in response to intravenous angiotensin II was studied in five goats. For comparison, the pre- and post-lesion cortisol responses to intravenous endotoxin were also evaluated. The cortisol response to angiotensin was extinguished in two goats, whereas a slightly attenuated response to endotoxin was still obtained post-lesioning. In these animals the lesions embraced the subfornical organ (SFO), the organum vasculosum of the lamina terminals (OVLT) and the interjacent anterior wall of the third ventricle. In two other goats, in which the SFO was completely destroyed but the OVLT remained largely intact, the lesions caused about 50% reduction of the cortisol response to angiotensin without any concomitant reduction of the response to endotoxin. It is concluded that ACTH-cortisol release in response to systemic angiotensin II is not mediated exclusively by receptors for the octapeptide confined to the SFO. Angiotensin receptors in the OVLT seem to be equally important in this respect.

Angiotensin acts at the subfornical organ to increase plasma oxytocin concentrations in the rat.

We have examined the effects of systemic angiotensin II (AII) on plasma oxytocin (OXY) concentrations in freely moving male Sprague-Dawley rats. We have also examined the role of the subfornical organ (SFO) as a CNS site at which circulating AII acts to influence secretion of this neurohypophysial peptide. OXY concentrations were measured by radioimmunoassay in plasma samples obtained by drawing blood samples through indwelling atrial catheters. In SFO intact animals (n = 8) AII infusion (1.0 microgram/kg/min) resulted in increases in plasma OXY concentrations from baseline values of 6.8 +/- 2.5 pg/ml to postinfusion concentrations of 44.9 +/- 11.9 pg/ml. In a second series of experiments electrolytic lesions were placed in the region of the SFO prior to testing the effects of AII infusion on OXY concentrations. Two further experimental groups were thus established according to the histologically verified location of lesions in either the rostral or caudal SFO. In the caudal SFO lesioned group AII infusion resulted in increases in plasma OXY concentrations from control values of 6.9 +/- 1.4 pg/ml to postinfusion levels of 45.1 +/- 9.8 pg/ml. These changes were not significantly different from the SFO intact group. In contrast rostral SFO lesions resulted in significantly elevated basal concentrations of OXY (17.4 +/- 3.4 pg/ml, n = 6) while postinfusion concentrations were found to be 22.8 +/- 4.9 pg/ml indicating that AII infusion was without effect following such lesions. These data are in accordance with the hypothesis that circulating AII acts at the SFO to influence SFO efferents which in turn activate OXY secreting neurons in the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei. These neuroendocrine cells then release this peptide into the systemic circulation from the posterior pituitary.