Analysis of afferent, central, and efferent components of the baroreceptor reflex in mice

Abstract

Studies of genetically modified mice provide a powerful approach to investigate consequences of altered gene expression in physiological and pathological states. The goal of the present study was to characterize afferent, central, and efferent components of the baroreceptor reflex in anesthetized Webster 4 mice. Baroreflex and baroreceptor afferent functions were characterized by measuring changes in renal sympathetic nerve activity (RSNA) and aortic depressor nerve activity (ADNA) in response to nitroprusside- and phenylephrine-induced changes in arterial pressure. The data were fit to a sigmoidal logistic function curve. Baroreflex diastolic pressure threshold (P(th)), the pressure at 50% inhibition of RSNA (P(mid)), and baroreflex gain (maximum slope) averaged 74 +/- 5 mmHg, 101 +/- 3 mmHg, and 2.30 +/- 0.54%/mmHg, respectively (n = 6). The P(th), P(mid), and gain for the diastolic pressure-ADNA relation (baroreceptor afferents) were similar to that observed for the overall reflex averaging 79 +/- 9 mmHg, 101 +/- 4 mmHg, and 2.92 +/- 0.53%/mmHg, respectively (n = 5). The central nervous system mediation of the baroreflex and the chronotropic responsiveness of the heart to vagal efferent activity were independently assessed by recording responses to electrical stimulation of the left ADN and the peripheral end of the right vagus nerve, respectively. Both ADN and vagal efferent stimulation induced frequency-dependent decreases in heart rate and arterial pressure. The heart rate response to ADN stimulation was nearly abolished in mice anesthetized with pentobarbital sodium (n = 4) compared with mice anesthetized with ketamine-acepromazine (n = 4), whereas the response to vagal efferent stimulation was equivalent under both types of anesthesia. Application of these techniques to studies of genetically manipulated mice can be used to identify molecular mechanisms of baroreflex function and to localize altered function to afferent, central, or efferent sites.

Mouse gene targeting in cardiovascular physiology

“…Nearly all values of cardiovascular parameters obtained in mice are well within the range predicted by allometric scaling equations from rats and humans (15). The baroreceptor reflex (22) and the regulation of fluid and electrolyte homeostasis by the renin-angiotensin system (8), two of the major blood pressure regulating systems (30,32), seem to function in a very similar fashion as in larger mammals.…”

“…Most relevant techniques and experimental protocols to assess cardiovascular function have now been adapted to the small size of the mouse. These include chronic measurements of blood pressure (6,14,21,23) and cardiac output (16), the analysis of the different components of the baroreceptor reflex (22), and renal function and balance studies (21). Many aspects of the murine cardiovascular system-anatomic and physiological-are identical to larger mammals.…”

Chronic intermittent hypoxia impairs baroreflex control of heart rate but enhances heart rate responses to vagal efferent stimulation in anesthetized mice

“…CIH significantly accelerated the HR responses to electrical stimulation at lower frequencies (P Ͻ 0.05). At high frequencies (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40), no difference was found between groups.…”

“…Previously, Ma et al (31) found that pentobarbital sodium selectively impaired reflex control of the HR and did not exert a major effect on reflex control of peripheral sympathetic nerve activity or vascular resistance in mice. Furthermore, the baroreflex response (sympathoexcitation) of renal sympathetic nerve activity (RSNA) during hypotension is largely attenuated, but baroreflex RSNA response (sympathoinhibition) during PE injection is rather complete in pentobarbital-anesthetized mice (31). Consistent with these observations, sympathoexcitation of RSNA during MABP decrease is dramatically blunted in inactin-anesthetized rats, but sympathoinhibition of RSNA to the increase of MABP seems similar to that in conscious rats (33,34).…”

Central Gene Transfer of Interleukin-10 Reduces Hypothalamic Inflammation and Evidence of Heart Failure in Rats After Myocardial Infarction

“…A technical limitation to be considered in interpreting the peripheral measures of HF is that the hemodynamic measurements and blood sampling were performed under pentobarbital anesthesia, Pentobarbital anesthesia is known to blunt sympathetic and cardiovascular responses, 50 and that effect may have diminished the differences between groups. Nonetheless, significant differences were observed in hemodynamics measurements and in plasma NE values in MI versus SHAM rats, and in MI rats treated with AdIL-10 versus ␤Gal.…”