The cardiovascular response of normal rats to dual lesion of the subfornical organ and area postrema at rest and to chronic losartan

Abstract

The subfornical organ (SFO) and the area postrema (AP), two of the sensory circumventricular organs (CVO), are known to play a role in the chronic central control of blood pressure. In previous studies in which these regions were independently lesioned, the chronic hypotensive effects of the AT(1) receptor blocker losartan (10 mg/kg/day) were attenuated by ~15 mm Hg. In the present study, we sought to investigate the effect of concurrent lesion of both the SFO and the AP on the cardiovascular effects of chronic losartan infusion in order to test the hypothesis that a greater attenuation of the hypotensive effects of losartan would be observed in rats with dual lesions. To do so, arterial pressure and heart rate responses to 10-day infusion of losartan were compared in sham rats and those with dual lesions of the AP and SFO. Two important findings resulted from this study. First, dual lesion rats exhibited a sustained and significant decrease in resting blood pressure (83+/-1 mm Hg vs. 104+/-1 mm Hg, respectively) and heart rate (356+/-3 bpm vs. 398+/-6 bpm, respectively) compared to sham animals. Secondly, rats with concurrent lesion of both the AP and the SFO demonstrated a significantly attenuated response to losartan compared to sham animals but showed no greater attenuation of losartan's chronic hypotensive effects than animals with lesion of either the SFO or the AP (approximately 15 mm Hg). Although these results do not support the stated hypothesis, they do suggest redundancy and compensatory roles of the AP and SFO in basal cardiovascular control.

Figure 1

Baseline averages of mean arterial pressure (top) and heart rate (bottom) in SFOAPx and SFOAPshm rats during control period. * P<0.05 between groups.

Figure 2

Daily averages of change in mean arterial pressure (top) and heart rate (bottom) relative to baseline control averages of SFOAPx and SFOAPshm rats during chronic infusion of losartan (10/mg/kg/d). * P<0.05 between groups.

Figure 3

Daily averages of total food intake in SFOAPx and SFOAPshm rats during control period and chronic infusion of losartan (10 mg/kg/d).

Figure 4

Daily averages of total sodium intake (top), sodium excretion (middle) and sodium balance (bottom) for SFOAPx and SFOAPshm rats during control period and chronic infusion of losartan (10 mg/kg/d).

Figure 5

Daily averages of total water intake (top), urine output (middle) and water balance (bottom) for SFOAPx and SFOAPshm rats during control period and chronic infusion of losartan (10 mg/kg/d).