Chronic angiotensin II infusion causes differential responses in regional sympathetic nerve activity in rats

Abstract

Angiotensin II (AngII)-induced hypertension in experimental animals has been proposed to be attributed in part to activation of the sympathetic nervous system. This sympathetic activation appears to be accentuated in animals consuming a high-salt diet (AngII-salt hypertension). However, accurate quantification of sympathetic activity is difficult, and controversy remains. It is particularly important to ask which are the critical vascular beds targeted by increased sympathetic nerve activity (SNA) in AngII-salt hypertension. To address this issue, mean arterial pressure and renal SNA or lumbar SNA were continuously recorded during a 5-day control period, 11 days of AngII (150 ng/kg per minute, SC), and a 5-day recovery period in conscious rats on a high-salt (2% NaCl) diet. Although mean arterial pressure reached a new steady-state level of 30 to 35 mm Hg above control levels by the end of the AngII period, renal SNA decreased by 40% during the first 7 days of AngII and then returned toward control levels by day 10 of AngII. In contrast, lumbar SNA remained at control levels throughout the AngII period. In another experiment we measured hindlimb norepinephrine spillover in conscious rats on normal (0.4%) or high- (2.0%) salt diets before and during 14 days of AngII administration. AngII had no significant affect on hindlimb norepinephrine spillover in either group. We conclude that chronic AngII modulates renal and lumbar SNAs differentially in rats consuming a high-salt diet and that AngII-salt hypertension in the rat is not caused by increased SNA to the renal or hindlimb vascular beds.

Figure 1

Representative data showing hourly values (top panel) for mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) in a single rat before, during and after AngII administration. Bottom shows 5 second traces for arterial pressure (AP) and RSNA on indicated days.

Figure 2

Group data shows the responses of mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA) and heart rate (HR) to AngII or vehicle administration in rats consuming a high salt diet. * = p < 0.05 compared to Control period (within group). # = p < 0.05 between groups.

Figure 3

Representative data showing hourly values (top panel) for mean arterial pressure (MAP) and lumbar sympathetic nerve activity (LSNA) in a single rat before, during and after AngII administration. Bottom shows 5 second traces for arterial pressure (AP) and LSNA on indicated days.

Figure 4

Group data showing the responses of mean arterial pressure (MAP), lumbar sympathetic nerve activity (LSNA) and heart rate (HR) to AngII or vehicle administration in rats consuming a high salt diet. * = p < 0.05 compared to Control period (within group). # = p < 0.05 between groups.

Figure 5

Response of mean arterial pressure (MA), hind-limb norepinephrine (NE) spillover, hind-limb flow and hind-limb resistance to AngII in rats on a normal (0.4%) salt diet (grey bars) or high salt (2.0%) salt diet (black bars). * = p < 0.05 compared to Control period (within group). # = p < 0.05 between groups.