AJP - Regulatory, Integrative and Comparative Physiology, Vol 267, Issue 5 1174-R1181, Copyright © 1994 by American Physiological Society
Novel angiotensin receptor subtypes in fowl
H. Nishimura, O. E. Walker, C. M. Patton, A. B. Madison, A. T. Chiu and J. Keiser
Department of Physiology and Biophysics, University of Tennessee, Memphis 38163.
We reported previously that blood vessels of domestic fowl contain
angiotensin (ANG) receptors on 1) endothelium, mediating vasorelaxation via
endothelium-derived relaxing factor and guanosine 3',5'-cyclic
monophosphate; 2) vascular smooth muscles, mediating neither relaxation nor
contraction; and 3) presumably adrenergic nerve endings, transmitting
vasopressor action via a release of norepinephrine. We aimed in the present
study to determine fowl vascular ANG receptor subtypes and relate them to
function. [Val5]ANG II (native fowl ANG II) increased mean arterial
pressure of anesthetized, ganglion-blocker-treated fowl. The dose-pressor
response curve for fowl ANG II was not altered by pretreatment (i.v.) with
the ANG receptor subtype 1 (AT1) antagonist Dup-753 (losartan, 10 mg/kg) or
the subtype 2 (AT2) antagonist PD-123319 (10 mg/kg). Furthermore,
cumulative doses (1-20 mg/kg) of losartan or PD-123319 did not selectively
inhibit ANG II-induced pressor responses. In reserpine- and
prazosin-treated anesthetized fowl, [Val5]ANG II caused dose-dependent
vasodepressor actions inhibited by neither losartan (10 mg/kg) nor
PD-123319 (10 mg/kg). Likewise, [Val5]ANG II-induced vasorelaxation of fowl
aortic rings in vitro was not inhibitable by PD-123319 or losartan (10(-5)
M). Specific binding of 125I-labeled ANG II to the aortic endothelium was
markedly displaced by ANG II, but not selectively by PD-123319 or losartan.
Specific binding of 125I-ANG II ligand to the membrane fraction of aortic
smooth muscles was displaced (50% inhibitory concentration) by [Val5]ANG II
(3.3 x 10(-8) M) and slightly by PD-123319 (3.7 x 10(-5) M), but not by
losartan or EXP-3174, an active metabolite of losartan.(ABSTRACT TRUNCATED
AT 250 WORDS)
