Dose-dependent systemic and renal haemodynamic effects of angiotensin II in conscious lambs: role of angiotensin AT1 and AT2 receptors.
The present experiments were designed to measure the effects of acute administration of angiotensin (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 s before (Control) and for 60 s after intravenous (i.v.) administration of one of 11 doses of ANG II (0-200 ng kg(-1)). Administration of ANG II was associated with a dose-dependent increase in MAP to a maximal effective concentration (EC100) of 100 ng kg(-1) in lambs aged 1 and 6 weeks. Administration of ANG II has caused a dose-dependent decrease in RBF, with EC100 values of 50 ng kg(-1) in 1-week-old lambs, and 25 ng kg(-1) in 6-week-old lambs. Responses to ANG II at the EC(50) were also measured in the presence of the specific ANG II AT(1) 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. In addition, MAP decreased and RBF increased in both age groups after administration of ZD 7155, but not PD 123319; the effects were similar in both age groups. These data provide new information that pressor and renal vasoconstrictor effects of ANG II during the first 6 weeks of postnatal life in lambs are elicited by activation of AT1 but not AT2 receptors.
Chappellaz
Mona L
ML
Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
Smith
Francine G
FG
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009287:Naphthyridines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology*; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects*; D012756:Sheep
D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D009287:Naphthyridines; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; C095905:ZD 7155; D000804:Angiotensin II; C073402:PD 123319