Angiotensin II control of regional haemodynamics in rats with aortocaval fistulae

Duggan, Daniel J. (2013) Angiotensin II control of regional haemodynamics in rats with aortocaval fistulae. Masters thesis, Memorial University of Newfoundland.

[English] PDF - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Download (6MB)

Abstract

Pathological conditions exist in which regional blood supply is reduced due to a decrease in arterial blood vessel lumen diameter. This may be accomplished by humoral or neurogenic vasoconstriction, or by arterial blood vessel hypertrophy. Adequate blood perfusion is important, and it is desirable to improve blood supply in these conditions. Rats with aortocaval fistulae (ACF) are models of heart failure in which regional blood supply is reduced and the renin-angiotensin-aldosterone system (RAAS) is activated. Attenuation of the RAAS was expected to cause a larger decrease in mean arterial pressure (MAP) and larger increases in regional blood flows and conductances (haemodynamics) in ACF rats than in sham-operated (SO) rats. Furthermore, AT₁ receptor antagonism by losartan was expected to cause larger effects on MAP and regional haemodynamics than AT₂ receptor antagonism by PD 123319. -- The continuous influence of angiotensin II on regional haemodynamics was estimated by administering captopril, losartan, and PD 1233 19 to rats with and without ACF. Losartan caused a larger decrease in MAP and generally larger increases in regional haemodynamics in rats with ACF than in SO rats. In rats with ACF, losartan caused a larger decrease in MAP and larger increases in regional conductances than the decreases produced by PD 123319. In SO rats, the increase in MAP produced by PD 123319 was larger than the decrease produced by losartan. The increases in mesenteric and renal conductances produced by losartan were larger than the decreases produced by PD 123319. However, the decrease in iliac conductance produced by PD 123319 was larger than that produced by losartan. -- The results of this study suggest (1) that the RAAS has a greater influence in controlling regional haemodynamics in rats with ACF than in SO rats and (2) that the RAAS is altered in rats with ACF to favor vasoconstriction, possibly as a mechanism of maintaining a normal mean arterial pressure despite a large decrease in total peripheral resistance. Finally, (3) AT₁ receptor antagonism is more effective than ACE inhibition at increasing regional blood flow in rats with ACF. This is important, given the goal of increasing regional blood supply in these rats, and may be true of other pathological conditions in which tissue ischaemia results from systemic vasoconstriction and decreased systemic blood flow.

Actions (login required)

View Item