The vasodilatory action of telmisartan on isolated mesenteric artery rings from rats

Document Type: Original Article

Authors

Department of Hematology, Navy General Hospital of PLA, Beijing, China

Abstract

Objective(s): Angiotensin Ⅱ type 1 receptor blockers (ARBs) represent one of the widely used antihypertensive agents. In addition to anti-hypertension effect, some ARBs also show other molecular effects such as activating peroxisome proliferator-activated receptor-γ and so on. Here we studied the effects of telmisartan on the rat isolated mesenteric artery rings pre-contracted by phenylephrine (PE).
Materials and Methods:Rat mesenteric artery rings were pre-contracted with 10 μM PE, and cumulative concentration-response curves to telmisartan were obtained. The endothelium-dependent mechanisms were investigated by mechanical removal of the endothelium. K+ channels were investigated by pretreatment of the artery rings with various K+ channel blockers.
Results:Telmisartan produced concentration-dependent relaxation of the artery rings pre-contracted by 10 μM PE. Denudation of the endothelium did not affect the relaxant effect of telmisartan. Pretreatment with BaCl2 nearly inhibited the relaxation induced by the 0.5, 1, 5 and 10 μM telmisartan, but did not affect the relaxation induced by the 50 and 100 μM telmisartan. While the relaxation induced by telmisartan was not affected by pretreatment with TEA, 4-AP and glibenclamide.
Conclusion:These findings demonstrated that telmisartan produces concentration dependent vasodilation in isolated rat mesenteric artery rings with or without endothelium pre-contracted by PE. KIR channel may be involved in such a relaxant effect of telmisartan.

Keywords


1.Ferrario CM, Strawn WB. Role of the renin-angiotensin-aldosterone system and proinfla-mmatory mediators in cardiovascular disease. Am J Cardiol 2006;98:121-128.

2.Underwood PC, Adler GK. The renin angiotensin aldosterone system and insulin resistance in humans. Curr Hypertens Rep 2013; 15:59-70.

3.Proudfoot JM, Croft KD, Puddey IB, Beilin LJ. Angiotensin II type 1 receptor antagonists inhibit basal as well as low-density lipoprotein and platelet-activating factor-stimulated human monocyte chemoattractant protein-1. J Pharmacol Exp Ther 2003; 305:846-853.

4.Clasen R, Schupp M, Foryst-Ludwig A, Sprang C, Clemenz M, Krikov M, et al. PPARgamma-activating angiotensin type-1 receptor blockers induce adiponectin. Hypertension 2005; 46:137-143.

5.Stangier J, Su CA, Roth W. Pharmacokinetics of orally and intravenously administered telmisartan in healthy young and elderly volunteers and in hypertensive patients. J Int Med Res 2000; 28:149-167.

6.Benson SC, Pershadsingh HA, Ho CI, Chittiboyina A, Desai P, Pravenec M, et al. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity. Hypertension 2004; 43:993-1002.

7.Matsuda K, Uruno A, Kogure N, Sugawara K, Shimada H, Nezu M, et al. Angiotensin II receptor blockers differentially affect CYP11B2 expression in human adrenal H295R cells. Mol Cell Endocrinol 2014; 383:60-68.

8.Tu DN, Liao YH, Zou AR, Du YM, Run Q, Wang XP, et al. Electropharmacological properties of telmisartan in blocking hKv1.5 and HERG potassium channels expressed on Xenopus laevis oocytes. Acta Pharmacol Sin 2008; 29:913-922.

9.Yamada S, Ano N, Toda K, Kitaoka A, Shiono K, Inoue G, et al. Telmisartan but not candesartan affects adiponectin expression in vivo and in vitro. Hypertens Res 2008; 31:601-606.

10. Huang Y, Chan FL, Lau CW, Tsang SY, Chen ZY, He GW, et al. Roles of cyclic AMP and Ca2+-activated K+ channels in endothelium-independent relaxation by urocortin in the rat coronary artery. Cardiovasc Res 2003; 57:824-833.

11. Gavras H, Lever AF, Brown JJ, Macadam RF, Robertson JI. Acute renal failure, tubular necrosis, and myocardial infarction induced in the rabbit by intravenous angiotensin II. Lancet 1971; 2:19-22.

12. Brunner HR, Laragh JH, Baer L, Newton MA, Goodwin FT, Krakoff LR, et al. Essential hypertension: renin and aldosterone, heart attack and stroke. N Engl J Med 1972; 286:441-449.

13. Mallat SG. Dual renin-angiotensin system inhibition for prevention of renal and cardiovascular events: do the latest trials challenge existing evidence? Cardiovasc Diabetol 2013; 12:108.

14. Michel MC, Foster C, Brunner HR, Liu L. A systematic comparison of the properties of clinically used angiotensin II type 1 receptor antagonists. Pharmacol Rev 2013; 65:809-848.

15. Li MW, Wang XP, Gao CY, Zou AR. Effects of telmisartan on voltage-gated Kv1.3 and Kv1.5 potassium channels expressed in Xenopus oocytes. Zhonghua Xin Xue Guan Bing Za Zhi 2009; 37:165-168.

16. Luo J, Ma KT, Zhang YM, Si JQ, Liang P, Li J. Effects of telmisartan on 4-Aminopyridine-sensitive voltage dependant potassium channel of lymphocyte derived from spontaneously hypertensive rat. Zhonghua Xin Xue Guan Bing Za Zhi 2010; 38:751-754.

17.  Mitchell JA, Ali F, Bailey L, Moreno L, Harrington LS. Role of nitric oxide and prostacyclin as vasoactive hormones released by the endothelium. Exp Physiol 2008; 93:141-147.

18. Nagao T, Vanhoutte PM. Endothelium-derived hyperpolarizing factor and endothelium-dependent relaxations. Am J Respir Cell Mol Biol 1993; 8:1-6.

19. Chen GP, Ye Y, Li L, Yang Y, Qian AB, Hu SJ. Endothelium-independent vasorelaxant effect of sodium ferulate on rat thoracic aorta. Life Sci 2009; 84:81-88.

20. Ko EA, Han J, Jung ID, Park WS. Physiological roles of K+ channels in vascular smooth muscle cells. J Smooth Muscle Res 2008; 44:65-81.

21. Rembold CM. Regulation of contraction and relaxation in arterial smooth muscle. Hypertension 1992; 20:129-137.