Potential role of intermittent functioning of baroreflexes in the etiology of hypertension in spontaneously hypertensive rats
Feng Gu, E. Benjamin Randall, Steven Whitesall, Kimber Converso-Baran, Brian E. Carlson, Gregory D. Fink, Daniel E. Michele, Daniel A. Beard
Feng Gu, E. Benjamin Randall, Steven Whitesall, Kimber Converso-Baran, Brian E. Carlson, Gregory D. Fink, Daniel E. Michele, Daniel A. Beard
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Research Article Cardiology

Potential role of intermittent functioning of baroreflexes in the etiology of hypertension in spontaneously hypertensive rats

Abstract

The spontaneously hypertensive rat (SHR) is a genetic model of primary hypertension with an etiology that includes sympathetic overdrive. To elucidate the neurogenic mechanisms underlying the pathophysiology of this model, we analyzed the dynamic baroreflex response to spontaneous fluctuations in arterial pressure in conscious SHRs, as well as in the Wistar-Kyoto (WKY), the Dahl salt-sensitive, the Dahl salt-resistant, and the Sprague-Dawley rat. Observations revealed the existence of long intermittent periods (lasting up to several minutes) of engagement and disengagement of baroreflex control of heart rate. Analysis of these intermittent periods revealed a predictive relationship between increased mean arterial pressure and progressive baroreflex disengagement that was present in the SHR and WKY strains but absent in others. This relationship yielded the hypothesis that a lower proportion of engagement versus disengagement of the baroreflex in SHR compared with WKY contributes to the hypertension (or increased blood pressure) in SHR compared with WKY. Results of experiments using sinoaortic baroreceptor denervation were consistent with the hypothesis that dysfunction of the baroreflex contributes to the etiology of hypertension in the SHR. Thus, this study provides experimental evidence for the roles of the baroreflex in long-term arterial pressure regulation and in the etiology of primary hypertension in this animal model.

Authors

Feng Gu, E. Benjamin Randall, Steven Whitesall, Kimber Converso-Baran, Brian E. Carlson, Gregory D. Fink, Daniel E. Michele, Daniel A. Beard

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Figure 5

Temporal trends in MAP during on and off states.

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Temporal trends in MAP during on and off states. Trends in MAP recorded ...
Trends in MAP recorded during all on and off states longer than 20 seconds are illustrated for 15-week-old SHR animals during baroreflex-off states (A) and -on states (B), for 15-week WKY animals during baroreflex-off states (C) and -on states (D), and for 15-week SD animals during baroreflex-off periods (E) and -on periods (F). In these time series, time 0 represents the onset of the switch to an on or off state. The solid black curves represent the mean trends for each case and the gray area represents ±1 SEM. The averages of MAP at the beginning and after 20 seconds in the off state are plotted for 7-, 10-, and 15-week SHR (A), WKY (C), and SD (E) animals. The averages of MAP at the beginning and after 20 seconds in the on state are plotted for 7-, 10-, and 15-week SHR (B), WKY (D), and SD (F) animals. The MAP tends to decrease during the first 20 seconds in on states and increase during the first 20 seconds in off states in SHR and WKY animals. These trends are not apparent in SD animals. Changes in pressure observed over the first 20 seconds of off and on states are summarized for SHR, WKY, and SD animals at 7, 10, and 15 weeks of age (G). The rate of pressure increase during off states increases and the rate of pressure decrease during on states decreases with age in the SHR. In panel A through panel F, data are shown as mean ± SEM. In panel G, data are shown in box-and-whisker plots (10%–90%). Paired 2-tailed Student’s t test: *P < 0.05, **P < 0.01.