Related Experiment Videos
UL-FS 49 (zatebradine) does not affect arterial baroreflex in conscious normal or aortic-constricted rats
M Sakamoto1, F M Siri, S B Solomon
1Department of Anesthesiology, Kumamoto University School of Medicine, Kumamoto City, Japan.
Insights
The novel bradycardic agent UL-FS 49 effectively reduces heart rate without impacting arterial baroreflex sensitivity (BRS) in normal rats and those with hypertension and left ventricular hypertrophy.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Baroreflex Regulation
Background:
- Heart rate reduction is crucial in managing cardiac conditions like ischemia and angina.
- Left ventricular hypertrophy can impair cardiovascular reflexes, including the arterial baroreflex.
- UL-FS 49 is a new bradycardic agent with a proposed selective action on the sinoatrial node.
Purpose of the Study:
- To investigate the effects of UL-FS 49 on arterial baroreflex sensitivity (BRS).
- To assess UL-FS 49's impact in normal rats and in a model of left ventricular hypertrophy and hypertension.
Main Methods:
- Arterial baroreflex sensitivity (BRS) was measured in normal rats, sham-operated rats, and rats with abdominal aortic constriction (AC)-induced left ventricular hypertrophy.
- BRS was calculated as the slope of the relationship between mean arterial pressure and RR interval.
- The effects of varying doses of UL-FS 49 on BRS were evaluated in all groups.
Main Results:
- Rats with AC exhibited significantly elevated mean arterial pressure and left ventricular mass.
- As anticipated, BRS was significantly reduced in the AC group compared to controls.
- UL-FS 49 demonstrated dose-dependent bradycardic effects across all groups but did not significantly alter BRS.
Conclusions:
- UL-FS 49 exerts potent bradycardic effects without compromising arterial baroreflex function.
- The arterial baroreflex is largely unaffected by UL-FS 49 in normal rats and in models of hypertension and left ventricular hypertrophy.
Abstract:
Heart-rate reduction is an important element of patient management during cardiac bypass surgery and in therapeutic measures for combating ischemia and relieving pain in patients with angina. UL-FS 49 is a novel bradycardic agent that purportedly acts solely on the sinoatrial node without potentially deleterious effects on arterial pressure and cardiac inotropism. However, little is known about influences of this agent on neuronal tissue and cardiovascular reflexes. Moreover, left ventricular hypertrophy, which often accompanies cardiovascular disease, is known to attenuate the arterial baroreflex and could have effects interactive 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 with left ventricular hypertrophy 14 days after abdominal aortic constriction (AC), and sham-operated controls (SH). Arterial baroreflex sensitivity (BRS) was estimated as the slope of the relation between mean arterial pressure (independent variable) and the RR interval (dependent variable). At the time of study, the AC group had significantly greater mean arterial pressure than either SH or N (159 +/- 2, 122 +/- 3, and 124 +/- 3 mm Hg, respectively; mean +/- SEM, p < 0.01) and significantly greater left ventricular mass to body mass ratio than did SH (3.73 +/- 0.11, 2.33 +/- 0.11 mg/g; p < 0.01). As expected, BRS was significantly 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). Despite its potent dose-dependent bradycardic effects in all three groups, UL-FS 49 did not affect BRS significantly in any group. These results show that the arterial baroreflex is largely unaffected by UL-FS 49 in both normal rats and rats with systemic hypertension and left ventricular hypertrophy.