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 8weeks. I Na, I CaL, I to, and membrane capacitance were measured in the left ventricular myocytes after 8weeks 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±0.19mg/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±0.86mA; P<0.01). PD123319 enhanced membrane capacitance compared with the non-PD123319 group (PD123319 vs. non-PD123319, 283.63±5.80 vs. 276.50±4.28pF; P<0.05). PD123319 increased the density of I CaL compared with the non-PD123319 group (PD123319 vs. non-PD123319, -6.76±0.48 vs. -6.13±0.30pA/pF; P<0.05). PD123319 decreased the density of I to compared 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.