Abstract P204: Food Restriction Increases the Cardiovascular Response Evoked by Angiotensin-[1-10] and Angiotensin-[1-7] in Female Fischer Rats

Anorexia is associated with cardiovascular dysfunction including hypotension, bradycardia and cardiac arrhythmias. In a rat model of food restriction (FR)-induced hypotension and bradycardia, we previously demonstrated that the activity of endothelial α1 adrenergic receptors and brain type 1 angiotensin receptors (AT1R) were increased. The aim of this study was to determine the role of the vasodilator, angiotensin (Ang)-[1-7] and the precursor Ang-[I-10] in the periphery and brain. Methods: Female Fischer rats (220g, 4 mo) were maintained for 14 days on a FR diet, that was 40% of the control group (C) food intake. Cannulas were implanted in the lateral ventricle (LV) on day 7. On day 14, the animals were catheterized with a polyethylene tube in the femoral artery for recording of mean arterial pressure (MAP) and heart rate (HR). Results: After 14 days, body weight (g) [C: 202±2, n=13 vs. FR: 176±2, n=14; p<0.05], MAP (mm Hg) [C: 105±1, n=35 vs. FR: 102±2, n=36; p<0.05] and HR (bpm) [C: 386±5, n=35 vs. FR: 353±8, n=36, p<0.001) were reduced in the FR compared to control rats. Injection of Ang-[1-7] caused a greater increase in MAP (Δ mm Hg) in the FR compared to C group when delivered either into the LV (25pmol) (C: Δ -2±1, n=8 vs. FR: Δ 7±1, n=10; p<0.05) or the femoral vein (1910pmol) [C: Δ 1±1, n=9 vs. FR: Δ 3±1, n=6; p<0.05]. Moreover, there was a greater increase in HR (Δ bpm) in the FR compared to the C group after LV injection (C: Δ 9±3, n=8 vs FR: Δ 29±9, n=10; p<0.05). Injection of Ang-[I-10] caused a greater increase in MAP (Δ mm Hg) in the FR compared to C group when delivered into the LV (25pmol) (C: 5±1, n=7 vs. FR: 13±2, n=7; p<0.005) or i.v (1910pmol) (C: Δ 1±1, n=7 vs. FR: Δ 15±2, n=8; p<0.05); however, there was no effect on HR. This Ang-[l-10]-induced increase in MAP was attenuated by administering captopril into the LV, in both the FR and C groups, suggesting this increase in MAP was mediated by angiotensin converting enzyme. Conclusion: These results suggest that increased Ang-[1-7] and Ang-[I-10] activity both in the periphery and brain play a role in the increased sympathetic activity observed in anorexia.