Maeso R, Rodrigo E, Muñoz-Garcia R, Navarro-Cid J, Ruilope L M, Lahera V, Cachofeiro V
Department of Physiology, School of Medicine, Universidad Complutense, Madrid, Spain.
J Hypertens. 1997 Dec;15(12 Pt 2):1677-84. doi: 10.1097/00004872-199715120-00072.
Our study was designed to investigate whether angiotensin II subtype 1 (AT1) receptors are involved in the constrictor responses evoked by endothelin-1 and the thromboxane A2 analogue U46619 in aortic rings from spontaneously hypertensive rats (SHR), by studying the effect of the AT1 receptor antagonist losartan. In addition, since nitric oxide seems to participate in the mechanism of action of losartan, we studied the effect of the nitric oxide synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on the action of losartan.
Dose-response curves of either endothelin-1 (10(-10) to 10(-7) mol/l) or U46619 (10(-10) to 10(-6) mol/l) were studied in the presence or absence of losartan (10(-5) mol/l) in aortic rings from SHR. Likewise, similar experiments were done in aortic rings pretreated with the nitric oxide synthesis inhibitor, L-NAME (10(-4) mol/l).
Pre-incubation with losartan significantly reduced the contractile response to endothelin-1 compared with control rings, without modifying the value represented by 50% of the maximal response (pD2). The concentration-response curve to U46619 was shifted to the right in the presence of losartan, reducing the pD2 compared with control rings. The presence of captopril (10(-5) mol/l) in the incubation media did not alter the response to either endothelin-1 or U46619. The diminished response to both endothelin-1 and U46619 in the presence of losartan was reversed in L-NAME-pretreated rings.
Angiotensin II seems to participate in the vasoconstriction induced by both endothelin-1 and the thromboxane A2 analogue through the stimulation of AT1 receptors in SHR aortic rings, because losartan inhibited this effect. Moreover, nitric oxide appears to be involved in this action of losartan.
本研究旨在通过研究血管紧张素II 1型（AT1）受体拮抗剂氯沙坦的作用，探讨AT1受体是否参与自发性高血压大鼠（SHR）主动脉环中内皮素-1和血栓素A2类似物U46619诱发的收缩反应。此外，由于一氧化氮似乎参与氯沙坦的作用机制，我们研究了一氧化氮合成抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）对氯沙坦作用的影响。
在存在或不存在氯沙坦（10⁻⁵ mol/L）的情况下，研究SHR主动脉环中内皮素-1（10⁻¹⁰至10⁻⁷ mol/L）或U46619（10⁻¹⁰至10⁻⁶ mol/L）的剂量反应曲线。同样，在用一氧化氮合成抑制剂L-NAME（10⁻⁴ mol/L）预处理的主动脉环中进行类似实验。
与对照环相比，预先用氯沙坦孵育可显著降低对内皮素-1的收缩反应，但不改变最大反应的50%（pD2）所代表的值。在存在氯沙坦的情况下，对U46619的浓度反应曲线向右移动，与对照环相比降低了pD2。孵育介质中存在卡托普利（10⁻⁵ mol/L）不会改变对内皮素-1或U46619的反应。在L-NAME预处理的环中，氯沙坦存在时对内皮素-1和U46619的反应减弱得以逆转。
血管紧张素II似乎通过刺激SHR主动脉环中的AT1受体参与内皮素-1和血栓素A2类似物诱导的血管收缩，因为氯沙坦可抑制这种作用。此外，一氧化氮似乎参与氯沙坦的这一作用。
