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.

Role of renal nerves in development of hypertension in DOCA-salt model in rats: a telemetric approach.

Centrally mediated hyperactivity of the autonomic nervous system contributes to DOCA hypertension; however, the targeted peripheral vascular bed(s) remain unclear. We propose that if renal sympathetic activity is a factor in the development of DOCA-salt hypertension, then renal denervation (RDNX) should attenuate the hypertensive response. In protocol 1, uninephrectomized RDNX (n = 9) and sham-denervated (n = 6) Sprague-Dawley rats were allowed free access to 0.9% NaCl solution and 0.1% NaCl diet. Mean arterial pressure (MAP) and heart rate were telemetrically recorded for 4 days before and 36 days after DOCA (100 mg/rat) implantation; sodium and water balances were recorded daily. Protocol 2 was similar except that saline intake in sham rats (n = 7) was matched to that observed in RDNX rats of protocol 1 for 30 days; for the last 10 days, the rats were allowed free access to saline. Before DOCA in protocol 1, MAP was lower (P < 0.05) in RDNX rats (99 +/- 1 mmHg) compared with sham rats (111 +/- 3 mmHg); however, heart rate and sodium and water balances were similar between groups. RDNX attenuated the MAP response to DOCA by approximately 50% (DeltaMAP = 22 +/- 3 mmHg, where Delta is change in MAP) when compared with sham rats (DeltaMAP = 38 +/- 6). RDNX rats consumed significantly less saline than sham rats, and cumulative sodium and water balances were reduced by 33% and 23%, respectively. In protocol 2, a similar pattern in MAP elevation was observed in RDNX and saline-restricted, sham-denervated rats even when saline restriction was removed. These results indicate that the renal sympathetic nerves are important in hypertension development but that other factors are also involved.