Endothelin-1- and acetylcholine-mediated effects in human and rat vessels: impact of perivascular adipose tissue, diabetes, angiotensin II, and chemerin.

IF 1.8 4区医学

Blood Pressure Pub Date : 2024-12-01 Epub Date: 2024-10-10 DOI:10.1080/08037051.2024.2414072

Edwyn O Cruz-López, Lunbo Tan, Daniël G Stolk, Antoon J van den Bogaerdt, Koen Verdonk, A H Jan Danser

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引用次数: 0

Abstract

Objective: To study the role of perivascular adipose tissue (PVAT) in the reactivity of rat and human vessels.

Methods: Iliac and mesenteric arteries were obtained from normotensive Sprague-Dawley rats, hypertensive transgenic (mRen2)27 rats overexpressing mouse renin, and (mRen2)27 rats made diabetic with streptozotocin. Human coronary arteries were obtained from donors. Concentration-response curves were constructed to endothelin-1 and acetylcholine with and without PVAT. The contribution of NO and endothelium-dependent hyperpolarization (EDH) were determined making use of the NO synthase inhibitor L-NAME and the EDH inhibitors apamin + TRAM-34. The endothelin type A and type B (ET_A, ET_B) receptor blockers BQ123 and BQ788, the chemerin inhibitors α-NETA and pravastatin, and the angiotensin receptor blocker losartan were also used.

Results: In rat iliac arteries, PVAT diminished endothelin-induced constriction, while the opposite was true in human coronaries. Coronary effects were unaltered by α-NETA, pravastatin, or losartan. ET_B receptor-mediated relaxation in iliac arteries occurred only with PVAT, and BQ123 blocked endothelin-1-induced constriction. Diabetes upregulated the anticontractile effects of PVAT. In rat mesenteric arteries, acetylcholine-induced relaxation with PVAT relied on NO, and on NO + EDH without PVAT. Diabetes upregulated the EDH component exclusively with PVAT.

Conclusion: PVAT modulates ET-1-induced constriction in a vessel type-dependent manner. Its enhancing effects in coronaries involved neither chemerin nor angiotensin II. Its anticontractile effects in rat iliac arteries involved ET_B receptor-mediated relaxation. Diabetes upregulated PVAT's anticontractile effects. In mesenteric arteries, PVAT counterbalanced the EDH component of the relaxant effect of acetylcholine. Diabetes reversed this effect by upregulating the EDH component.

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人和大鼠血管中内皮素-1 和乙酰胆碱介导的效应：血管周围脂肪组织、糖尿病、血管紧张素 II 和螯合素的影响。

目的：研究血管周围脂肪组织（PVAT）在大鼠和人体血管反应性中的作用：研究血管周围脂肪组织（PVAT）在大鼠和人类血管反应性中的作用：方法：从血压正常的 Sprague-Dawley 大鼠、过度表达小鼠肾素的高血压转基因（mRen2）27 大鼠和用链脲佐菌素治疗糖尿病的（mRen2）27 大鼠身上获取髂动脉和肠系膜动脉。人体冠状动脉取自供体。在有或没有 PVAT 的情况下，构建了内皮素-1 和乙酰胆碱的浓度-反应曲线。使用 NO 合酶抑制剂 L-NAME 和 EDH 抑制剂 apamin + TRAM-34 测定了 NO 和内皮依赖性超极化（EDH）的贡献。此外还使用了内皮素 A 型和 B 型（ETA、ETB）受体阻断剂 BQ123 和 BQ788、螯合素抑制剂 α-NETA 和普伐他汀以及血管紧张素受体阻断剂洛沙坦：结果：在大鼠髂动脉中，PVAT 可减少内皮素诱导的收缩，而在人体冠状动脉中则相反。α-NETA、普伐他汀或洛沙坦对冠状动脉的影响没有改变。ETB 受体介导的髂动脉松弛仅发生于 PVAT，BQ123 阻止了内皮素-1 诱导的收缩。糖尿病会增强 PVAT 的抗收缩作用。在大鼠肠系膜动脉中，乙酰胆碱诱导的 PVAT 松弛依赖于 NO，而无 PVAT 时则依赖于 NO + EDH。糖尿病只能通过 PVAT 上调 EDH 成分：结论：PVAT 以依赖血管类型的方式调节 ET-1 诱导的收缩。它对冠状动脉的增强作用既不涉及螯合素，也不涉及血管紧张素 II。它对大鼠髂动脉的抗收缩作用涉及 ETB 受体介导的松弛。糖尿病会增强 PVAT 的抗收缩作用。在肠系膜动脉中，PVAT 抵消了乙酰胆碱松弛作用中的 EDH 成分。糖尿病通过上调EDH成分逆转了这种效应。

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来源期刊

Blood Pressure Medicine-Cardiology and Cardiovascular Medicine

CiteScore

3.20

自引率

5.60%

发文量

期刊介绍： For outstanding coverage of the latest advances in hypertension research, turn to Blood Pressure, a primary source for authoritative and timely information on all aspects of hypertension research and management. Features include: • Physiology and pathophysiology of blood pressure regulation • Primary and secondary hypertension • Cerebrovascular and cardiovascular complications of hypertension • Detection, treatment and follow-up of hypertension • Non pharmacological and pharmacological management • Large outcome trials in hypertension.