Chronic baroreflex activation restores spontaneous baroreflex control and variability of heart rate in obesity-induced hypertension

Abstract

The sensitivity of baroreflex control of heart rate is depressed in subjects with obesity hypertension, which increases the risk for cardiac arrhythmias. The mechanisms are not fully known, and there are no therapies to improve this dysfunction. To determine the cardiovascular dynamic effects of progressive increases in body weight leading to obesity and hypertension in dogs fed a high-fat diet, 24-h continuous recordings of spontaneous fluctuations in blood pressure and heart rate were analyzed in the time and frequency domains. Furthermore, we investigated whether autonomic mechanisms stimulated by chronic baroreflex activation and renal denervation-current therapies in patients with resistant hypertension, who are commonly obese-restore cardiovascular dynamic control. Increases in body weight to ∼150% of control led to a gradual increase in mean arterial pressure to 17 ± 3 mmHg above control (100 ± 2 mmHg) after 4 wk on the high-fat diet. In contrast to the gradual increase in arterial pressure, tachycardia, attenuated chronotropic baroreflex responses, and reduced heart rate variability were manifest within 1-4 days on high-fat intake, reaching 130 ± 4 beats per minute (bpm) (control = 86 ± 3 bpm) and ∼45% and <20%, respectively, of control levels. Subsequently, both baroreflex activation and renal denervation abolished the hypertension. However, only baroreflex activation effectively attenuated the tachycardia and restored cardiac baroreflex sensitivity and heart rate variability. These findings suggest that baroreflex activation therapy may reduce the risk factors for cardiac arrhythmias as well as lower arterial pressure.

Keywords: baroreflex; heart rate variability; hypertension; obesity; sympathetic nervous system.

Fig. 1.

Changes in mean arterial pressure (A) and heart rate (B) during Developing Obesity and responses to prolonged baroreflex activation (PBA) and renal denervation during Established Obesity. Values are means ± SE (n = 6). *P < 0.05 vs. mean of days 2–3 of Control (C); †P < 0.05 vs. mean of days 33–34 of Established Obesity; #P < 0.05 vs. mean of days 47–48 of Recovery (REC) after PBA.

Fig. 2.

Changes of baroreflex sensitivity indexes in time domain [sequence analysis (A)] and frequency domain [volume of transfer gain throughout the day across frequencies <0.5 Hz (B) and <0.1 Hz (C)] during Developing Obesity and responses to PBA and renal denervation during Established Obesity. Values are means ± SE (n = 6). *P < 0.05 vs. mean of days 2–3 of Control; †P < 0.05 vs. mean of days 33–34 of Established Obesity; #P < 0.05 vs. mean of days 47–48 of Recovery after PBA.

Fig. 3.

Changes in pulse interval (PI) variability indexes in time domain (short-term variability, A) and frequency domain (volume of power across frequencies <0.5 Hz throughout the day, B) during Developing Obesity and responses to PBA and renal denervation during Established Obesity. Values are means ± SE (n = 6). *P < 0.05 vs. mean of days 2–3 of Control; †P < 0.05 vs. mean of days 33–34 of Established Obesity; #P < 0.05 vs. mean of days 47–48 of Recovery after PBA.

Fig. 4.

Contour plots of sequential power spectra of PI oscillations for frequencies up to 0.5 Hz throughout the day (normalized units). The color range is logarithmic, with orange representing the highest and violet the lowest power.

Fig. 5.

Changes in systolic blood pressure (SBP) variability indexes in time domain (short-term variability, A) and frequency domain (volume of power across frequencies <0.5 Hz throughout the day, B) during Developing Obesity and responses to PBA and renal denervation during Established Obesity. Values are means ± SE (n = 6). *P < 0.05 vs. mean of days 2–3 of Control; †P < 0.05 vs. mean of days 33–34 of Established Obesity; #P < 0.05 vs. mean of days 47–48 of Recovery after PBA.