title: Angiotensin II control of regional haemodynamics in rats with aortocaval fistula.
abstract: What is the central question of this study? Hyperdynamic circulation because of arteriovenous fistula results in reduction of blood flow to organs but is a model of low circulatory resistance with activated renin-angiotensin system. The aim was to determine contributions of different subtypes of angiotensin II receptors to regional blood flow and vascular conductance in a hyperdynamic circulatory state. What is the main finding and its importance? The renin-angiotensin system plays a pivotal role in control of regional blood flow in animals with arteriovenous fistula and makes a major contribution to the maintenance of normal arterial blood pressure. In this hyperdynamic circulatory state model, angiotensin II type 1 receptors predominated in regulating regional haemodynamics. Regional perfusion is reduced and the renin-angiotensin system activated in rats with aortocaval fistula. The effects of captopril (angiotensin-converting enzyme inhibitor), losartan (angiotensin II type 1 receptor antagonist) and PD 123319 (angiotensin II type 2 receptor antagonist) on regional blood flow and vascular conductance were assessed in rats with aortocaval fistula and sham-operated rats. Control of blood flow and vascular conductance by angiotensin II was evaluated by serial bolus injections of captopril, losartan and PD 123319 in anaesthetized rats. In rats with fistula, PD 123319 significantly decreased, whereas captopril and losartan increased, mesenteric blood flow. The decrease in mesenteric blood flow induced by PD 123319 was significantly greater in rats with fistula compared with sham operation. Captopril and PD 123319 significantly decreased renal blood flow compared with losartan, which increased it. In sham-operated rats, captopril and losartan significantly increased, whereas PD 123319 decreased, mesenteric and renal conductance. In rats with fistula, captopril and losartan significantly increased, whereas PD 123319 decreased, mesenteric conductance. The significant increase produced by losartan on mesenteric conductance was greater in rats with fistula compared with sham operation. PD 123319 produced a significantly greater decrease in renal conductance of rats with aortocaval fistula compared with sham-operated rats. Captopril, losartan and PD 123319 did not significantly affect perfusion in the hindquarter in rats with fistula or sham-operated. The renin-angiotensin system is more active in the control of regional haemodynamics in rats with aortocaval fistula and acts as a mechanism of maintaining normal arterial blood pressure in these animals. In rats with fistula, angiotensin II type 1 receptors predominate in regulating regional haemodynamics.
authors.affiliation: Division of BioMedical Sciences, Faculty of Medicine, Memorial University, St John's, Newfoundland and Labrador, Canada.
authors.forename: Daniel J
authors.identifier: http://orcid.org/0000-0002-3756-9968
authors.initials: DJ
authors.lastname: Duggan
authors.affiliation: Division of BioMedical Sciences, Faculty of Medicine, Memorial University, St John's, Newfoundland and Labrador, Canada.
authors.forename: Reza
authors.initials: R
authors.lastname: Tabrizchi