Do angiotensin type 2 receptors modulate haemodynamic effects of type 1 receptors in conscious newborn lambs?
OBJECTIVE
It was hypothesized that in the immediate newborn period, when the renin-angiotensin system (RAS) is activated, angiotensin type 2 receptors (AT2Rs) buffer the haemodynamic effects of angiotensin type 1 receptors (AT1Rs), as occurs in adult animals when the RAS is activated.


METHODS
Arterial (systolic, diastolic, and mean) pressures (SAP, DAP, MAP), mean venous pressures (MVP) and renal blood flows (RBF) were measured in conscious, chronically instrumented lambs aged ~1 (8±2 days, N=8) and 6 weeks (41±4 days, N=11). In each animal, measurements were made before and after administration of the selective AT1R antagonist ZD 7155 (experiment one) and the selective AT2R antagonist PD123319 (experiment two) as well as both antagonists, ZD 7155 and PD 123319 (experiment three).


RESULTS
Haemodynamic responses to combined inhibition of both AT1Rs and AT2Rs were similar to inhibition of AT1Rs alone: there was a significant decrease in SAP, DAP, and MAP and a significant increase in RBF within minutes of concomitant administration of ZD 7155 and PD 123319 in both age groups. These responses were similar to responses to ZD 7155 alone, whereas PD 123319 alone did not alter any of the measured variables.


CONCLUSIONS
AT2Rs do not counterbalance the pressor and renal vasoconstrictor effects elicited by activation of AT1Rs in the immediate newborn period. During this time, AT1Rs appear to predominate in eliciting the haemodynamic effects of angiotensin II (ANG II), whereas the role of the upregulated AT2Rs remains elusive.
University of Calgary, Calgary, Alberta, Canada.
Angela E
AE
Vinturache
University of Calgary, Calgary, Alberta, Canada fsmith@ucalgary.ca.
Francine G
FG
Smith
D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness / Q000187:drug effects; D003971:Diastole / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D008297:Male; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D012756:Sheep; D013599:Systole / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D057912:Angiotensin II Type 2 Receptor Blockers; D044139:Receptor, Angiotensin, Type 2
ANG II; AT1R; AT2R; Neonate; cardiovascular; haemodynamics; physiology