title: Long-term treatment of spontaneously hypertensive rats with PD123319 and electrophysiological remodeling of left ventricular myocardium.
abstract: To investigate the effects of PD123319, an antagonist of angiotensin II subtype-2 receptor (AT2R), on the electrophysiological characteristics of the left ventricular hypertrophic myocardium in spontaneously hypertensive rats (SHR). A total of twenty-four 10-week-old male SHR were divided into two groups: PD123319 and non-PD123319 groups (n = 12 in each). Twelve 10-week-old Wistar-Kyoto rats served as the control group. Systolic blood pressure, left ventricular mass index (LVMI), ventricular effective refractory period, and ventricular fibrillation threshold were also measured after 8 weeks. INa, ICaL, Ito, and membrane capacitance were measured in the left ventricular myocytes after 8 weeks by whole-cell patch clamp. PD123319 increased LVMI compared with the non-PD123319 group (PD123319 vs. non-PD123319, 3.83 ± 0.11 vs. 3.60 ± 0.19 mg/g; P < 0.01). PD123319 also decreased the ventricular fibrillation threshold compared with the non-PD123319 group (PD123319 vs. non-PD123319, 14.75 ± 0.65 vs. 16.0 ± 0.86 mA; P < 0.01). PD123319 enhanced membrane capacitance compared with the non-PD123319 group (PD123319 vs. non-PD123319, 283.63 ± 5.80 vs. 276.50 ± 4.28 pF; P < 0.05). PD123319 increased the density of ICaLcompared with the non-PD123319 group (PD123319 vs. non-PD123319, -6.76 ± 0.48 vs. -6.13 ± 0.30 pA/pF; P < 0.05). PD123319 decreased the density of Itocompared with the non-PD123319 group (PD123319 vs. non-PD123319, 11.49 ± 0.50 vs. 12.23 ± 0.36 pA/pF; P < 0.05). Long-term treatment with PD123319 worsened the development of myocyte hypertrophy and associated electrophysiological alterations in spontaneously hypertensive rat.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ying
authors.affiliation: Department of Respiratory Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Guan
authors.initials: G
authors.lastname: Kai-Pan
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Long
authors.initials: L
authors.lastname: Wei-Qing
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Long-Yun
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Wu
authors.initials: W
authors.lastname: De-Xi
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. hzbin2603@163.com.
authors.forename: Huang
authors.initials: H
authors.lastname: Zhi-Bin
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D057912:Angiotensin II Type 2 Receptor Blockers / Q000633:toxicity*; D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D025802:Electric Capacitance; D006352:Heart Ventricles / Q000187:drug effects* / Q000503:physiopathology; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced* / Q000503:physiopathology; D007093:Imidazoles / Q000633:toxicity*; D008297:Male; D011725:Pyridines / Q000633:toxicity*; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000139:chemically induced* / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D057912:Angiotensin II Type 2 Receptor Blockers; D000959:Antihypertensive Agents; D007093:Imidazoles; D011725:Pyridines; C073402:PD 123319
keywords: Electrophysiology; Hypertension; Hypertrophy; PD123319