Long-term treatment of spontaneously hypertensive rats with PD123319 and electrophysiological remodeling of left ventricular myocardium.

Naunyn-Schmiedeberg's archives of pharmacology

PubMedID: 27629578

Ying X, Kai-Pan G, Wei-Qing L, Long-Yun P, De-Xi W, Zhi-Bin H. Long-term treatment of spontaneously hypertensive rats with PD123319 and electrophysiological remodeling of left ventricular myocardium. Naunyn Schmiedebergs Arch Pharmacol. 2016;.
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. I Na, I CaL, I to, 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 I CaL compared 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 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.