Angiotensin II type 2 receptor - Mediated vasodilation in human coronary microarteries

被引:149
|
作者
Batenburg, WW
Garrelds, IM
Bernasconi, CC
Juillerat-Jeanneret, L
van Kats, JP
Saxena, PR
Danser, AHJ
机构
[1] Erasmus MC, Dept Pharmacol, NL-3015 GE Rotterdam, Netherlands
[2] Erasmus MC, Dept Thorac Surg, NL-3015 GE Rotterdam, Netherlands
[3] Erasmus MC, Heart Valve Bank, NL-3015 GE Rotterdam, Netherlands
[4] Univ Lausanne, Inst Pathol, Lausanne, Switzerland
关键词
angiotensin; bradykinin; microcirculation; nitric oxide; vasodilation;
D O I
10.1161/01.CIR.0000128696.12245.57
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background - Angiotensin (Ang) II type 2 (AT(2)) receptor stimulation results in coronary vasodilation in the rat heart. In contrast, AT(2) receptor - mediated vasodilation could not be observed in large human coronary arteries. We studied Ang II - induced vasodilation of human coronary microarteries (HCMAs). Methods and Results - HCMAs (diameter, 160 to 500 mum) were obtained from 49 heart valve donors ( age, 3 to 65 years). Ang II constricted HCMAs, mounted in Mulvany myographs, in a concentration-dependent manner (pEC(50), 8.6 +/- 0.2; maximal effect [E-max], 79 +/- 13% of the contraction to 100 mmol/L K+). The Ang II type 1 receptor antagonist irbesartan prevented this vasoconstriction, whereas the AT(2) receptor antagonist PD123319 increased Emax to 97 +/- 14% (P < 0.05). The increase in Emax was larger in older donors ( correlation Delta E-max versus age, r = 0.47, P < 0.05). The PD123319-induced potentiation was not observed in the presence of the NO synthase inhibitor L-NAME, the bradykinin type 2 (B-2) receptor antagonist Hoe140, or after removal of the endothelium. Ang II relaxed U46619-preconstricted HCMAs in the presence of irbesartan by maximally 49 +/- 16%, and PD123319 prevented this relaxation. Finally, radioligand binding studies and reverse transcription - polymerase chain reaction confirmed the expression of AT(2) receptors in HCMAs. Conclusions - AT(2) receptor - mediated vasodilation in the human heart appears to be limited to coronary microarteries and is mediated by B-2 receptors and NO. Most likely, AT(2) receptors are located on endothelial cells, and their contribution increases with age.
引用
收藏
页码:2296 / 2301
页数:6
相关论文
共 50 条
  • [31] Angiotensin II type 1 receptor-mediated peroxide production in human macrophages
    Yanagitani, Y
    Rakugi, H
    Okamura, A
    Moriguchi, K
    Takiuchi, S
    Ohishi, M
    Suzuki, K
    Higaki, J
    Ogihara, T
    HYPERTENSION, 1999, 33 (01) : 335 - 339
  • [32] Angiotensin II type 2 receptor mediated angiotensin II and high glucose induced decrease in renal prorenin/renin receptor expression
    He, Ming
    Zhang, Lin
    Shao, Ying
    Xue, Hong
    Zhou, Li
    Wang, Xiao-Fang
    Yu, Chen
    Yao, Tai
    Lu, Li-Min
    MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2010, 315 (1-2) : 188 - 194
  • [33] Enhanced Angiotensin Type 2 Receptor-Mediated Vasodilation and Blood Flow in Uterine Arteries of Pregnant Rats
    Mishra, Jay
    More, Amar
    Hankins, Gary
    Sathishkumar, Kunju
    REPRODUCTIVE SCIENCES, 2015, 22 : 65A - 65A
  • [34] Angiotensin II induces the generation of procoagulant microparticles by human mononuclear cells via an angiotensin type 2 receptor-mediated pathway
    Cordazzo, Cinzia
    Neri, Tommaso
    Petrini, Silvia
    Lombardi, Stefania
    Balia, Cristina
    Cianchetti, Silvana
    Carmazzi, Yuri
    Paggiaro, Pierluigi
    Pedrinelli, Roberto
    Celi, Alessandro
    THROMBOSIS RESEARCH, 2013, 131 (04) : E168 - E174
  • [35] FUNCTIONAL ANGIOTENSIN II TYPE 2 RECEPTORS MEDIATE BOTH VASOCONSTRICTION AND VASODILATION IN THE HUMAN FOREARM CIRCULATION
    Schinzari, F.
    Tesauro, M.
    Rovella, V.
    Mores, N.
    Cardillo, C.
    JOURNAL OF HYPERTENSION, 2010, 28 : E11 - E11
  • [36] Vascular angiotensin II actions mediated by angiotensin II type 2 receptors
    Ruth E. Hannan
    Robert E. Widdop
    Current Hypertension Reports, 2004, 6 : 117 - 123
  • [37] The angiotensin II type 2 receptor in the brain
    Horiuchi, Masatsugu
    Mogi, Masaki
    Iwai, Masaru
    JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM, 2010, 11 (01) : 1 - 6
  • [38] Is the angiotensin II type 2 receptor cerebroprotective?
    Fournier, A
    Achard, JM
    Boutitie, F
    Mazouz, H
    Mansour, J
    Oprisiu, R
    Fernandez, L
    Messerli, F
    CURRENT HYPERTENSION REPORTS, 2004, 6 (03) : 182 - 189
  • [39] The angiotensin II type 2 receptor and the kidney
    Siragy, Helmy M.
    JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM, 2010, 11 (01) : 33 - 36
  • [40] Is the angiotensin ii type 2 receptor cerebroprotective?
    Albert Fournier
    Jean Michel Achard
    Florent Boutitie
    Hakim Mazouz
    Janette Mansour
    Roxana Oprisiu
    Leonardo Fernandez
    Franz Messerli
    Current Hypertension Reports, 2004, 6 : 182 - 189