Nishimura H, Walker O E, Patton C M, Madison A B, Chiu A T, Keiser J
Department of Physiology and Biophysics, University of Tennessee, Memphis 38163.
Am J Physiol. 1994 Nov;267(5 Pt 2):R1174-81. doi: 10.1152/ajpregu.1994.267.5.R1174.
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)
我们之前报道过，家禽的血管在以下部位含有血管紧张素（ANG）受体：1）内皮，通过内皮衍生的舒张因子和鸟苷3',5'-环磷酸介导血管舒张；2）血管平滑肌，既不介导舒张也不介导收缩；3）推测为肾上腺素能神经末梢，通过去甲肾上腺素的释放传递升压作用。我们在本研究中的目的是确定家禽血管ANG受体亚型并将它们与功能联系起来。[Val5]ANG II（天然家禽ANG II）增加了经神经节阻滞剂处理的麻醉家禽的平均动脉压。家禽ANG II的剂量-升压反应曲线在经血管紧张素受体亚型1（AT1）拮抗剂Dup-753（氯沙坦，10 mg/kg）或亚型2（AT2）拮抗剂PD-123319（10 mg/kg）静脉预处理后未改变。此外，氯沙坦或PD-123319的累积剂量（1 - 20 mg/kg）并未选择性抑制ANG II诱导的升压反应。在经利血平和哌唑嗪处理的麻醉家禽中，[Val5]ANG II引起剂量依赖性的血管降压作用，氯沙坦（10 mg/kg）和PD-123319（10 mg/kg）均不能抑制。同样，[Val5]ANG II在体外诱导的家禽主动脉环血管舒张也不能被PD-123319或氯沙坦（10⁻⁵ M）抑制。¹²⁵I标记的ANG II与主动脉内皮的特异性结合被ANG II显著取代，但未被PD-123319或氯沙坦选择性取代。¹²⁵I-ANG II配体与主动脉平滑肌膜部分的特异性结合被[Val5]ANG II（3.3×10⁻⁸ M）取代（半数抑制浓度），被PD-123319（3.7×10⁻⁵ M）轻微取代，但未被氯沙坦或氯沙坦的活性代谢物EXP-3174取代。（摘要截断于250字）
