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| 標題: | Angiotensin II blockers improve cardiac coronary flow under hemodynamic pressure overload |
| 作者: | Chang, Wei-Ting
Fisch, Sudeshna
Dangwal, Seema
Chen, Michael
Cheng, Susan
Chen, Zhih-Cherng
Liao, Ronglih |
| 貢獻者: | Natl Cheng Kung Univ, Coll Med, Inst Clin Med
Chi Mei Med Ctr, Dept Cardiol
Southern Taiwan Univ Sci & Technol, Dept Biotechnol
Harvard Med Sch, Dept Med, Brigham & Womens Hosp, Boston
Stanford Univ, Stanford Cardiovasc Inst, Dept Med, Sch Med
Smidt Heart Inst Cedars Sinai Med Ctr, Barbra Streisand Womens Heart Ctr
Chia Nan Univ Pharm & Sci, Dept Pharm |
| 關鍵字: | Coronary flow velocity
Hypertension
Angiotensin receptor blockers
Calcium channel blockers
Cardiac fibrosis |
| 日期: | 2021 |
| 上傳時間: | 2023-11-11 11:56:10 (UTC+8) |
| 出版者: | SPRINGERNATURE |
| 摘要: | Coronary flow velocity (CFV) is reduced in pathologic cardiac hypertrophy. This functional reduction is linked to adverse cardiac remodeling, hypertension and fibrosis, and angiotensin II (AngII) is a key molecular player. Angiotensin receptor blockers (ARBs) are known to attenuate adverse cardiac remodeling and fibrosis following increased afterload, while the mechanism by which these drugs offer clinical benefits and regulate hemodynamics remains unknown. To establish a direct connection between coronary flow changes and angiotensin-induced hypertension, we used a Doppler echocardiographic method in two distinct disease models. First, we performed serial echocardiography to visualize coronary flow and assess heart function in patients newly diagnosed with hypertension and currently on ARBs or calcium channel blockers (CCBs). CFV improved significantly in the hypertensive patients after 12 weeks of ARB treatment but not in those treated with CCBs. Second, using murine models of pressure overload, including Ang II infusion and aortic banding, we mimicked the clinical conditions of Ang II- and mechanical stress-induced hypertension, respectively. Both Ang II infusion and aortic banding increased the end-systolic pressure-volume relationship and cardiac fibrosis, but interestingly, only Ang II infusion resulted in a significant reduction in CFV and corresponding activation of pressure-sensitive proteins, including connective tissue growth factor, hypoxia-inducible factor 1 alpha and signal transducer and activator of transcription 3. These data support the existence of a molecular and functional link between AngII-induced hemodynamic remodeling and alterations in coronary vasculature, which, in part, can explain the clinical benefit of ARB treatment in hypertensive patients. |
| 關聯: | HYPERTENS RES, v.44, n.7, pp.803-812 |
| 顯示於類別: | [藥學系(所)] 期刊論文
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