Blood Pressure (Dec 2024)

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

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

DOI
https://doi.org/10.1080/08037051.2024.2414072
Journal volume & issue
Vol. 33, no. 1

Abstract

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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 (ETA, ETB) 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. ETB 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 ETB 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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