UL-FS-49 (ZATEBRADINE) DOES NOT AFFECT ARTERIAL BAROREFLEX IN CONSCIOUS NORMAL OR AORTIC-CONSTRICTED RATS

Heart-rate reduction is an important element of patient management dur ing cardiac bypass surgery and in therapeutic measures for combating i schemia and relieving pain in patients with angina. UL-FS 49 is a nove l bradycardic agent that purportedly acts solely on the sinoatrial nod e without potentially deleterious effects on arterial pressure and car diac inotropism. However, little is known about influences of this age nt on neuronal tissue and cardiovascular reflexes. Moreover, left vent ricular hypertrophy, which often accompanies cardiovascular disease, i s known to attenuate the arterial baroreflex and could have effects in teractive with those of UL-FS 49. In this study, the effects of UL-FS 49 on the arterial baroreflex were tested in normal rats (N), rats wit h left ventricular hypertrophy 14 days after abdominal aortic constric tion (AC), and sham-operated controls (SH). Arterial baroreflex sensit ivity (BRS) was estimated as the slope of the relation between mean ar terial pressure (independent variable) and the RR interval (dependent variable). At the time of study, the AC group had significantly greate r mean arterial pressure than either SH or N (159 +/- 2, 122 +/- 3, an d 124 +/- 3 mm Hg, respectively; mean +/- SEM, p < 0.01) and significa ntly greater left ventricular mass to body mass ratio than did SH (3.7 3 +/- 0.11, 2.33 +/- 0.11 mg/g; p < 0.01). As expected, BRS was signif icantly depressed in AC, compared with either SH or N (0.52 +/- 0.16, 1.48 +/- 0.12, 1.69 +/- 0.25 ms/mm Hg, respectively; p < 0.01). Despit e its potent dose-dependent bradycardic effects in all three groups, U L-FS 49 did not affect BRS significantly in any group. These results s how that the arterial baroreflex is largely unaffected by UL-FS 49 in both normal rats and rats with systemic hypertension and left ventricu lar hypertrophy.