In this series of experiments, we addressed the question whether ethanol-evoked attenuation of the baroreflex bradycardic response is dependent on either or both sets of the baroreceptor afferents. In the first study, bilateral transection of the aortic nerves in the cervical region,

Figure 21.1 Bar graphs showing that ethanol (0.1, 0.5 and 1.0 g/kg) produces graded decreases in regression coefficient (baroreflex slopes; beats/min/mmHg) in SO, but not in aortic barodenervated (ABD) rats. Values are expressed as mean ± S.E.M.; *p < 0.05 compared to base-line value. Number of rats in each group is shown in parentheses; with permission [28],

Figure 21.1 Bar graphs showing that ethanol (0.1, 0.5 and 1.0 g/kg) produces graded decreases in regression coefficient (baroreflex slopes; beats/min/mmHg) in SO, but not in aortic barodenervated (ABD) rats. Values are expressed as mean ± S.E.M.; *p < 0.05 compared to base-line value. Number of rats in each group is shown in parentheses; with permission [28], or sham operation, was conducted under methohexital anesthesia. Post-operative care was performed as described in accordance with the institutional guidelines [28], Following a 2-3 day recovery, the baroreflex sensitivity was significantly attenuated in aortic denervated as compared with sham operated rats [28], As in our previous studies [21,22], ethanol caused a dose-related attenuation of the baroreflex-mediated bradycardia in sham operated rats (Figure 21.1) [28], However, such an effect of ethanol was absent in aortic barodenervated rats (Figure 21.1). These findings suggest that ethanol selectively acts on the aortic baroreflex arc to depress the baroreflex-mediated bradycardia in intact rats [28], It was important to consider the possibility that consequent changes in body functions caused by aortic

Figure 21.2 Baroreflex curves relating decreases in HR to PE-induced elevations in BP obtained in conscious freely moving ABD or SO rats before and after i. v. administration of an anesthetizing dose of pentobarbital (30 mg/kg). In either group, pentobarbital produced a downward shift in the curve as evident by a reduction in the regression coefficient (baroreflex slope; inset). Values are expressed as mean ± S.E.M.; *p < 0.05 compared to prepentobarbital values (ANOVA). Number of rats in each group is shown in parentheses; with permission [281.

Figure 21.2 Baroreflex curves relating decreases in HR to PE-induced elevations in BP obtained in conscious freely moving ABD or SO rats before and after i. v. administration of an anesthetizing dose of pentobarbital (30 mg/kg). In either group, pentobarbital produced a downward shift in the curve as evident by a reduction in the regression coefficient (baroreflex slope; inset). Values are expressed as mean ± S.E.M.; *p < 0.05 compared to prepentobarbital values (ANOVA). Number of rats in each group is shown in parentheses; with permission [281.

barodenervation may have contributed to the lack of ethanol action on baroreflexes in this animal model. An expected effect of aortic barodenervation is the increase in blood pressure, which we observed while the rats were under anesthesia and for the following 24 hrs after recovery [28], If it persisted, a higher blood pressure in aortic barodenervated rats may have confounded the data interpretation. However, by 48-72 hrs after barodenervation, the time at which the effect of ethanol was investigated, blood pressure had subsided to control levels [28],

Another possibility that needed to be considered was the significantly lower baseline baroreflex sensitivity in aortic barodenervated rats, which persisted even after blood pressure subsided to control levels [28], The depressant effect of ethanol on baroreflex sensitivity may be obscured by the lower baseline BRS value, which may not be lowered any more by any intervention. To address this issue, an anesthetizing dose of pentobarbital was administered to aortic barodenervated and control rats. As shown in Figure 21.2, pentobarbital depressed the baroreflex sensitivity to a similar degree in both preparations [28], These results ruled out the low baroreflex sensitivity, in aortic barodenervated rats, as a cause for the absence of ethanol action. Therefore, the results of this investigation, in conscious rats, suggest a major role for the aortic baroreceptors in the ethanol-evoked attenuation of baroreflex sensitivity [28],

Figure 21.3 The effect of ethanol (1 g/kg) on baroreflex curves relating changes in HR to rises in BP evoked by PE in conscious unrestrained CBD and SO rats. Note that ethanol, but not saline, causes a significant (*p < 0.05, ANOVA) downward shift in the baroreflex curves in both groups of rats as compared to pre-ethanol values. Values shown are the regression coefficients ofbaroreflex curves in beats per minute per millimeter of mercury; the number of rats in each group is shown in parentheses; with permission [29],

Figure 21.3 The effect of ethanol (1 g/kg) on baroreflex curves relating changes in HR to rises in BP evoked by PE in conscious unrestrained CBD and SO rats. Note that ethanol, but not saline, causes a significant (*p < 0.05, ANOVA) downward shift in the baroreflex curves in both groups of rats as compared to pre-ethanol values. Values shown are the regression coefficients ofbaroreflex curves in beats per minute per millimeter of mercury; the number of rats in each group is shown in parentheses; with permission [29],

Figure 21.4 Bar graphs showing the capacity of ethanol (1 g/kg) to produce a significant reduction in the regression coefficient (baroreflex slopes; beats/min/ mmHg) ofPE-baroreflex curves. Values are expressed as mean ± S.E.M.; # and *p < 0.05 compared to base-line and after-saline values, respectively. CBD, carotid barodenervation. The number of rats in each group is shown in parentheses; with permission [29],

Figure 21.4 Bar graphs showing the capacity of ethanol (1 g/kg) to produce a significant reduction in the regression coefficient (baroreflex slopes; beats/min/ mmHg) ofPE-baroreflex curves. Values are expressed as mean ± S.E.M.; # and *p < 0.05 compared to base-line and after-saline values, respectively. CBD, carotid barodenervation. The number of rats in each group is shown in parentheses; with permission [29],

Direct evidence was sought to further support the pivotal role of the aortic baroafferents in ethanol-evoked attenuation ofbaroreflex mediated bradycardia. In this study, the rats were subjected to carotid barodenervation and the aortic nerves were left intact [29], Similar pressor and tachycardic responses to those observed following aortic barodenervation were obtained during the first 24hr [28,29], These hemodynamic responses subsided to control levels by 2-3 days after carotid barodenervation but the baroreflex sensitivity remained significantly attenuated [29], In effect, the latter was similar in magnitude to the level obtained in aortic barodenervated rats [28,29], In support of the hypothesis, ethanol attenuated the baroreflex sensitivity in carotid barodenervated rats in spite of the low basal value (Figures 21,3, 21,4) [29], Taken together, these findings provide evidence that implicates the aortic baroreceptors and their projections in the depressant action of ethanol of baroreceptor-mediated bradycardia [28,29],

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