Novel angiotensin receptor subtypes in fowl
Nishimura, H.; Walker, O.E.; Patton, C.M.; Madison, A.B.; Chiu, A.T.; Keiser, J.
American Journal of Physiology 267(5 Pt 2): R1174-R1181
1994
ISSN/ISBN: 0002-9513 PMID: 7977843 Document Number: 432274
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. (Val-5)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 (iv) with the ANG receptor subtype 1 (AT-1) antagonist Dup-753 (losartan, 10 mg/kg) or the subtype 2 (AT-2) 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, (Val-5)ANG II caused dose-dependent vasodepressor actions inhibited by neither losartan (10 mg/kg) nor PD-123319 (10 mg/kg). Likewise, (Val-5)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 (Val-5)ANG II (3.3 times 10-8 M) and slightly by PD-123319 (3.7 times 10-5 M), but not by losartan or EXP-3174, an active metabolite of losartan. These results suggest that the ANG receptors on fowl endothelium, vascular smooth muscles, and presumably in adrenergic nerve endings differ from the AT-1 and AT-2 subtypes.