Received June 15, 2005
Revised July 5, 2005
Accepted after revision August 3, 2005
Dose-dependent systemic and renal haemodynamics effects of angiotensin II (ANG II) in conscious lambs: Role of AT1 and AT2 receptors
Mona Lynne Chappellaz 1
Francine Gabriel Smith 1*
1 University of Calgary
* To whom correspondence should be addressed. E-mail: fsmith{at}ucalgary.ca.
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Abstract |
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The present experiments were designed to measure the effects of acute administration of ANG II on mean arterial pressure (MAP) and renal blood flow (RBF) in conscious, chronically instrumented lambs at two different stages of postnatal maturation, and to determine the receptors through which these effects of ANG II are elicited. Experiments consisted of haemodynamic measurements for 10 seconds before (Control) and for sixty sec after administration of one of 11 doses of ANG II (0 to 200 ng·kg-1), administered in random order, at least twice, with 5 - 10 min between each dose. Administration of ANG II was associated with a dose-dependent increase in MAP to the EC100 of 100 ng·kg-1 in lambs aged both one and six weeks, and a dose-dependent decrease in RBF to the EC100 of 50 ng·kg-1 in one week old lambs and 25 ng·kg-1 in lambs aged six weeks. Responses to EC50 ANG II were also measured in the presence of the specific ANG II AT1 receptor antagonist, ZD 7155, the specific AT2 receptor antagonist, PD 123319, and vehicle. Administration of ZD 7155 but not PD 123319 or vehicle abolished the MAP and RBF responses to ANG II in both age groups of lambs. In addition, MAP decreased and RBF increased in both age groups of lambs after administration of ZD 7155, but not PD 123319, effects being similar in both age groups. These data provide new information that pressor and renal vasoconstrictor effects of ANG II during the first six weeks of postnatal life in lambs are elicited by activation of AT1 but not AT2 receptors.
Key Words:
Angiotensin, Neonate, Renal