OVLT lesion decreases basal arterial pressure and the chronic hypertensive response to AngII in rats on a high-salt diet

Abstract

We have reported that lesion of the organum vasculosum of the lamina terminalis (OVLT) has no effect on basal levels of mean arterial pressure (MAP) but abolishes the hypertensive effects of angiotensin II (AngII) in rats consuming a normal-salt diet. These results suggest that the OVLT does not contribute to regulation of MAP under conditions of normal salt intake, but it is an important brain site for the hypertensive actions of AngII. The OVLT has been proposed as a major sodium sensor in the brain and the hypertensive effects of AngII are exacerbated by high-salt intake. Therefore, the objective of this study was to investigate the role of the OVLT during AngII-induced hypertension in rats fed a high-salt diet. Male Sprague-Dawley rats underwent sham (Sham; n = 9) or OVLT lesion (OVLTx; n = 8) surgery and were placed on a high-salt (2% NaCl) diet. MAP was measured by radio telemetry during three control days, 10 days of AngII infusion (10 ng/kg/min, i.v.), and a 3-day recovery period. MAP was significantly lower in OVLTx (97 ± 2 mmHg) compared to Sham (106 ± 1 mmHg) rats during the control period (P < 0.05). Moreover, the chronic pressor response to AngII was markedly attenuated in OVLTx rats. MAP increased 58 ± 3 mmHg in Sham rats by Day 10 of AngII compared to a 40 ± 7 mmHg increase in OVLTx rats (P < 0.05). We conclude that (1) the OVLT regulates the basal levels of MAP in rats consuming a high-salt and (2) the OVLT is an important brain site of action for the pathogenesis of AngII-salt hypertension in the rat. Supported by HL076312.

Keywords: Angtiotensin II; OVLT; circumventricular organ; hypertension.

Figure 1

Photomicrographs of hypothalamic coronal sections from an organum vasculosum of the lamina terminalis (OVLT) (left) lesioned rat and from a sham (right)-lesioned rat showing an intact OVLT (*).

Figure 2

Average 24-h mean arterial pressure (A) and heart rate (B) recorded during saline infusion (3 days of control and recovery period) and 10 days of AngII infusion (10 ng kg⁻¹ min⁻¹) in organum vasculosum of the lamina terminalis (OVLT) and sham-lesioned rats. *P < 0.05 between lesioned and sham rats.

Figure 3

Change from baseline mean arterial pressure (A) and heart rate (B) recorded during saline infusion (3 days of recovery period) and 10 days of AngII infusion (10 ng kg⁻¹ min⁻¹) in organum vasculosum of the lamina terminalis (OVLT) and sham-lesioned rats. *P < 0.05 between lesioned and sham rats.

Figure 4

Average 24-h sodium intake (A) sodium output (B) and sodium balance (C) during saline infusion (3 days of control and recovery period) and 10 days of treatment in organum vasculosum of the lamina terminalis (OVLT) and sham-lesioned rats.

Figure 5

Average 24-h water intake (A) urine output (B) and water balance (C) during saline infusion (3 days of control and recovery period) and 10 days of treatment in organum vasculosum of the lamina terminalis (OVLT) and sham-lesioned rats.