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

Abstract

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.

Fig. 1.

Histological sections and schematic diagrams at the level of the subfornical organ (SFO). Representative coronal sections at the level of the SFO (arrows) from a sham-lesioned (A) and an SFO-lesioned rat (B) and corresponding coronal (C) and sagittal diagrams (D) are shown. All rats included in the final data analysis had lesions encompassing the stippled areas shown on the schematic. Staining in A and B is hematoxylin and eosin (×40 magnification). 3V, third ventricle; cc, corpus callosum; f, fornix; PVA, anterior part of the paraventricular thalamic nucleus; sm, stria medullaris; TS, triangular septal nucleus; vhc, ventral hippocampal commissure; Ch, choroid plexus. Diagrams in C and D are modified from the rat brain atlas of Paxinos and Watson (38a).

Fig. 2.

Changes in arterial pressure after lesioning of the SFO in individual rats. Systolic and diastolic arterial pressures in conscious sham-clipped (n = 6, top) and 2 kidney, 1 clip (2K,1C; n = 6, bottom) rats before (•) and 4 days after (○) lesioning of the SFO. Values for individual rats as well as means ± SE are shown. *P < 0.01 vs. prelesion in the same group. #P < 0.01 vs. prelesion in the sham-clipped group.

Fig. 3.

Representative reflex responses of renal sympathetic nerve activity (RSNA) in each of the 4 groups of rats. Reflex response of RSNA to phenylephrine (PE)-induced increases and nitroprusside (NP)-induced decreases in mean arterial pressure (MAP) are shown for sham-clipped, sham-lesioned (A), sham-clipped SFO-lesioned (SFOx; B), 2K,1C sham-lesioned (C), and 2K,1C SFOx rats (D).

Fig. 4.

Baroreflex curves of the heart rate (HR) response in the 4 groups of rats. Mean baroreflex curves of the HR response are shown for sham-clipped, sham-lesioned (•), sham-clipped SFOx (○), 2K,1C sham-lesioned (▾), and 2K,1C SFOx rats (▿). Inset depicts the baroreflex gain in the same groups. Symbols on the curves represent resting values (means ± SE). See Tables 2 and 3 for complete statistics and numbers in each group.

Fig. 5.

Baroreflex curves of the RSNA response in the 4 groups of rats. Mean baroreflex curves of the RSNA response are shown for sham-clipped, sham-lesioned (•), sham-clipped SFOx (○), 2K,1C sham-lesioned (▾), and 2K,1C SFOx rats (▿). Inset depicts the baroreflex gain in the same groups. Symbols on the curves represent resting values (means ± SE). See Tables 2 and 3 for complete statistics and numbers in each group.

Fig. 6.

MAP averaged over 24 h from telemetry recordings in the 4 groups of rats. MAP was for measured 5 days before and 5 days after SFOx or sham lesioning in 2K,1C or sham-clipped rats. Values are means ± SE; numbers in each group are as given in Table 3. *P < 0.05 vs. 2K,1C SFOx group. See results for other comparisons.