Subfornical organ differentially modulates baroreflex function in normotensive and two-kidney, one-clip hypertensive rats

During activation of the renin-angiotensin system, hindbrain circumventricular organs such as the area postrema have been implicated in modulating the arterial baroreflex. This study was undertaken to test the hypothesis that the subfornical organ (SFO), a forebrain circumventricular structure, may also modulate the baroreflex. Studies were performed in rats with two-kidney, one-clip (2K, 1C) hypertension as a model of endogenously activated renin-angiotensin system. Baroreflex function was ascertained during ramp infusions of phenylephrine and nitroprusside in conscious sham-clipped and 5-wk 2K, 1C rats with either a sham or electrolytically lesioned SFO. Lesioning significantly decreased mean arterial pressure in 2K, 1C rats from 158 +/- 7 to 131 +/- 4 mmHg but not in sham-clipped rats. SFO-lesioned, sham-clipped rats had a significantly higher upper plateau and range of the renal sympathetic nerve activity-mean arterial pressure relationship compared with sham-clipped rats with SFO ablation. In contrast, lesioning the SFO in 2K, 1C rats significantly decreased both the upper plateau and range of the baroreflex control of renal sympathetic nerve activity, but only the range of the baroreflex response of heart rate decreased. Thus, during unloading of the baroreceptors, the SFO differentially modulates the baroreflex responses in sham-clipped vs. 2K, 1C rats. Since lesioning the SFO did not influence plasma angiotensin II (ANG II), the effects of the SFO lesion are not caused by changes in circulating levels of ANG II. These findings support a pivotal role for the SFO in the sympathoexcitation observed in renovascular hypertension and in baroreflex regulation of sympathetic activity in both normal and hypertensive states.