Lesion of the OVLT markedly attenuates chronic DOCA-salt hypertension in rats

Abstract

Lesions of the anteroventral third ventricle (AV3V region) are known to prevent many forms of experimental hypertension, including mineralocorticoid [deoxycorticosterone acetate (DOCA)-salt] hypertension in the rat. However, AV3V lesions include the organum vasculosum of the lamina terminalis (OVLT), portions of the median preoptic nucleus, and efferent fibers from the subfornical organ (SFO), thereby limiting the ability to define the individual contribution of these structures to the prevention of experimental hypertension. Having previously reported that the SFO does not play a significant role in the development of DOCA-salt hypertension, the present study was designed to test the hypothesis that the OVLT is necessary for DOCA-salt hypertension in the rat. In uninephrectomized OVLT-lesioned (OVLTx; n = 6) and sham-operated ( n = 4) Sprague-Dawley rats consuming a 0.1% NaCl diet and 0.9% NaCl drinking solution, 24-h mean arterial pressure (MAP) was recorded telemetrically 5 days before and 21 days after DOCA implantation (100 mg sc per rat). No differences in control MAP were observed between groups. The chronic pressor response to DOCA was attenuated in OVLTx rats such that MAP increased to 133 ± 3 mmHg in sham-operated rats by day 21 of DOCA compared with 120 ± 4 mmHg (means ± SE) in OVLTx rats. These results support the hypothesis that the OVLT is an important brain site of action for the pathogenesis of DOCA-salt hypertension in the rat.

Keywords: DOCA-salt hypertension; myocardial infarction.

Fig. 1.

Timeline of study protocol and surgical procedures. DOCA, deoxycorticosterone acetate; NEPHx, nephrectomy; OVLTx, electrolytic ablation of the organum vasculosum of the lamina terminalis.

Fig. 2.

Photomicrographs of representative cresyl violet-stained 50-µm hypothalamic coronal sections from a sham-operated rat showing an intact organum vasculosum of the lamina terminalis (OVLT, *directly above OVLT, left) and from an OVLT-lesioned rat illustrating area of lesion (right). AC, anterior commissure.

Fig. 3.

Average 24-h mean arterial pressure (MAP, top) and heart rate (HR, bottom) recorded during 5 days of control period (rats began drinking saline) followed by 21 days after DOCA implantation (100-mg pellet sc per rat) in organum vasculosum of the lamina terminalis (OVLT)-lesioned (OVLTx) and sham-operated rats (OVLTsham). *P < 0.05 between lesioned and sham rats.

Fig. 4.

Average 24-h saline intake (top), urine output (middle), and water balance (bottom) during 5 days of control period (rats began drinking saline) followed by 21 days after DOCA implantation (100-mg pellet sc per rat) in organum vasculosum of the lamina terminalis (OVLT)-lesioned (OVLTx) and sham-operated rats (OVLTsham). *P < 0.05 between lesioned and sham rats.

Fig. 5.

Average 24-h sodium intake (top), sodium output (middle), and sodium balance (bottom) during 5 days of control period (rats began drinking saline) followed by 21 days after DOCA implantation (100-mg pellet sc per rat) in organum vasculosum of the lamina terminalis (OVLT)-lesioned (OVLTx) and sham-operated rats (OVLTsham). *P < 0.05 between lesioned and sham rats.