Seo B, Lüscher T F
Department of Research, University Hospital, Basel, Switzerland.
Hypertension. 1995 Apr;25(4 Pt 1):501-6. doi: 10.1161/01.hyp.25.4.501.
We characterized vascular endothelin receptors of the renal artery from adult (12 to 16 weeks of age) and old (72 to 76 weeks) spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). Vessels were suspended in organ chambers (37 degrees C, aerated with 95% O2/5% CO2), and isometric tension was recorded. The endothelin-A (ETA) receptor antagonist FR139317, the combined ETA/ETB receptor antagonist bosentan, and the ETB-selective agonist sarafotoxin S6c were used. In old (and less so in adult) SHR, cumulative concentration-contraction curves to endothelin-1 showed a small contraction resistant to FR139317 (10(-5) mol/L) at 3 x 10(-9) to 10(-8) mol/L endothelin-1, which was completely inhibited by bosentan (10(-5) mol/L). This FR139317-resistant contraction to endothelin-1 was not present in WKY. Furthermore, in the presence of FR139317 (10(-5) mol/L), sarafotoxin S6c induced a stronger contraction in old SHR than in WKY (P < .05). In rings contracted with norepinephrine, sarafotoxin S6c caused endothelium-dependent relaxations in both strains; these relaxations were blocked by N omega-nitro-L-arginine methyl ester, indicating that nitric oxide is the mediator. In WKY but not SHR, release of nitric oxide by sarafotoxin S6c increased with age (P < .05). Thus, both ETA and ETB receptors mediate contraction to endothelin-1 in the renal artery from SHR but not WKY. ETB receptors on vascular smooth muscle seem to be unmasked with age in SHR, whereas those on endothelium (mediating nitric oxide release) exhibit more efficient responses with age in WKY.
我们对成年（12至16周龄）和老年（72至76周龄）自发性高血压大鼠（SHR）以及年龄匹配的Wistar-Kyoto大鼠（WKY）肾动脉的血管内皮素受体进行了特征描述。将血管悬挂于器官浴槽中（37摄氏度，用95% O₂/5% CO₂通气），记录等长张力。使用了内皮素-A（ETA）受体拮抗剂FR139317、ETA/ETB受体联合拮抗剂波生坦以及ETB选择性激动剂萨拉毒素S6c。在老年（成年时程度稍轻）SHR中，内皮素-1的累积浓度-收缩曲线显示，在3×10⁻⁹至10⁻⁸摩尔/升内皮素-1时，对FR139317（10⁻⁵摩尔/升）有轻微收缩抵抗，而波生坦（10⁻⁵摩尔/升）可完全抑制该收缩。WKY中不存在这种对内皮素-1的FR139317抵抗性收缩。此外，在存在FR139317（10⁻⁵摩尔/升）的情况下，萨拉毒素S6c在老年SHR中诱导的收缩比在WKY中更强（P < 0.05）。在与去甲肾上腺素收缩的血管环中，萨拉毒素S6c在两种品系中均引起内皮依赖性舒张；这些舒张被N-ω-硝基-L-精氨酸甲酯阻断，表明一氧化氮是介质。在WKY而非SHR中，萨拉毒素S6c诱导的一氧化氮释放随年龄增加（P < 0.05）。因此，ETA和ETB受体均介导SHR而非WKY肾动脉对内皮素-1的收缩。在SHR中，血管平滑肌上的ETB受体似乎随年龄暴露，而在WKY中，内皮上的ETB受体（介导一氧化氮释放）随年龄表现出更有效的反应。
