Depressor Nerve Research Articles

Methods for exploring the morpho-functional relations of the aortic depressor nerve in experimental diabetes

The present study investigated morpho-functional relations of the aortic depressor nerve (ADN) 5, 15 and 120 days after the onset of streptozotocin-induced diabetes in rats. Time control animals received vehicle. Under pentobarbital anesthesia, ADN activity was recorded simultaneously with arterial pressure. After the recordings, nerves were prepared for light microscopy study and morphometry. ADN function was accessed by means of pressure-nerve activity curve (fitted by sigmoidal regression) and cross-spectral analysis between mean arterial pressure (MAP) and ADN activity. The relation between morphological (myelinated fibers number and density, total myelin area, total fiber area and percentage of occupancy) and functional (gain, signal/noise relation, frequency) parameters were accessed by linear regression analysis and correlation coefficient calculations. Functional parameters obtained by means of the sigmoidal regression curve as well as by cross-spectral analysis were similar in diabetic and control rats. Morphometric parameters of the ADN were similar between groups 5 days after the onset of diabetes. Average myelin area and myelinated fiber area were significantly smaller on diabetic rats 15 and 120 days after the onset of diabetes, being the myelinated fiber and respective axons area and diameter also smaller on 120 days group. Nevertheless, G ratio (ratio between axon and fiber diameter) was nearly 0.6 and not different between groups or experimental times. No significant relationship between morphological and functional parameters was detected in all experimental groups. The present study suggests that ADN diabetic neuropathy was time-dependent, with damage to myelinated fibers to be the primary event, not evidenced by physiological methods.

Attenuated baroreflex control of sympathetic nerve activity in obese Zucker rats by central mechanisms

Adult obese Zucker rats (OZRs) have reduced sympathetic responses to evoked changes in arterial pressure (AP) compared to lean Zucker rats (LZRs). This study examined whether attenuated sympathetic baroreflexes in OZRs may be due to altered sensory or central mechanisms. The OZRs had elevated baseline splanchnic sympathetic nerve activity (SNA) and mean AP (MAP) compared to age-matched LZRs under urethane anaesthesia (P < 0.05). Aortic depressor nerve activity (ADNA) was measured while AP was altered by infusions of phenylephrine or nitroprusside (+/-60 mmHg over 60-90 s) in rats treated with atropine and propranolol to eliminate changes in heart rate. Although baseline ADNA was higher in the hypertensive OZRs, the relationship between MAP and ADNA was comparable in OZRs and LZRs. In contrast, electrical stimulation of the ADN afferent fibres (5 s train, 2 ms pulses, 4 V, 0.5-48 Hz) produced dramatically smaller reductions in SNA and MAP in OZRs compared to LZRs (P < 0.05). After blockade of alpha-adrenergic receptors to prevent sympathetically mediated depressor responses, OZRs still had reduced sympathetic responses to stimulation of the ADN. In addition, stimulation of vagal afferent nerves electrically or with phenylbiguanide (1, 2, 4 and 8 microg, i.v.) produced smaller inhibitions of SNA in OZRs compared with LZRs (P < 0.05). These data suggest that attenuated sympathetic baroreflexes are the result of altered central mechanisms in OZRs, and not deficits in the responsiveness of aortic baroreceptors to AP. Furthermore, central deficits in the regulation of SNA in OZRs extend to other sympathoinhibitory reflexes initiated by vagal afferent nerves.

Expression of c‐Fos protein in the nucleus of tractus solitary (NTS) and paraventricular nucleus of the hypothalamus (PVN) elicited by electrical stimulation of the aortic depressor nerve in conscious L‐NAME‐induced hypertensive rats

To detect possible alterations of the baroreflex arch, we assessed the expression of c‐Fos in the NTS and PVN of L‐NAME‐induced hypertensive rats submitted to electrical stimulation of the aortic depressor nerve (ADN) in conscious state. Rats were treated for 14 days with L‐NAME (n=7), D‐NAME (n=5) or tap water (CONTROL; n=6). The animals were equipped with catheters in the femoral artery and vein, and a pair of electrodes for intermittent (5s on/10s off) electrical stimulation (1mA, 2ms and 60Hz) during 20 min. L‐NAME treated rats showed higher arterial pressure and heart rate than D‐NAME and CONTROL rats. The hypotensive response and bradycardia due to electrical stimulation did not differ among groups. The density of c‐Fos in the intermediate and commissural caudal NTS, and magnocelular and parvocelular portions of the PVN was higher in L‐NAME treated rats. In conclusion, electrical stimulation of the ADN activated more effectively neurons in the NTS and PVN of L‐NAME induced hypertensive rats. These findings suggest a greater buffering effect of the NTS upon the PVN in this hypertensive model.Supported by CAPES, CNPq and FAPESP.

Diet‐induced obesity differentially affects baroreflex‐mediated sympathetic and parasympathetic outflow

Diet‐induced obesity (DIO) impairs the baroreflex control of heart rate (HR), which may arise from differential influences of the sympathetic (SNS) and parasympathetic (PNS) nervous systems. To test this hypothesis, Δ mean arterial pressure (MAP) and Δ HR to 30‐sec maximal stimulation of the aortic baroreceptors (aortic depressor nerve; 20V, 100Hz) were recorded before and after muscarinic receptor blockade (MB; methscopolamine, iv bolus 500ug/kg) in inactin‐anesthetized male SD rats. Rats were fed a normal (N, 13.5% kcal fat) or high fat diet (HFD, 33% kcal fat) for 4–5 weeks. Rats fed the HFD were separated into obesity prone (OP) or resistant (OR) groups, based on the top and bottom tertile of weight gain, respectively. Baseline values did not differ between groups.As shown in the table above, Δ HR and Δ MAP were blunted in OP rats compared to N and OR rats (†p&lt;0.05 vs OP). Removal of PNS influence with MB attenuated Δ HR and Δ MAP in N and OR rats (*p&lt;0.05 control vs MB), which were similar to the OP rat control responses. MB had no effect on the OP group. These findings suggest that DIO impairs aortic baroreceptor activation of the PNS, but may minimally impact the SNS. Funded by AHA (Brooks) and NIH (McCully NS045553, Brooks HL088552, Andresen HL41119). Δ HR (bpm) Δ MAP (mmHg) Control MB Control MB N (n=6) −53±7† −28±4* −57±6† −47±4* OR (n=6) −45±6† −31±3* −60±5† −48±4* OP (n=6) −30±6 −28±6 −41±8 −47±4

ASIC2 dependent activation of the baroreceptors is required for the arterial baroreflex

We have shown that deletion of acid‐sensing ion channel (ASIC2) impairs baroreflex (BR) control of the circulation. This impairment may result from loss of baroreceptor sensitivity or loss of central neuronal responsiveness, or both. In these experiments we tested the contribution of the two components by inducing a reflex increase in arterial pressure with bilateral carotid occlusion (BCO) in WT (n=6) and congenic ASIC2 null mice (n=6). BCO reduces abruptly the arterial pressure (BP) in the carotid sinuses triggering a reflex increase in systemic BP which in turn is buffered by activation of the intact aortic baroreceptors and the aortic depressor nerves (ADNs). We found that the reflex increase in BP integrated over a 20 second period of BCO averaged 134±14 and 141±15 mmHg·sec in WT and ASIC2−/− respectively. However, following bilateral section of the ADNs, the increase in BP more than doubled in WT mice (to 283.4±20.3 mmHg·sec), but was unchanged in KO mice (143.8±13.8 mmHg·sec) suggesting that the buffering influence of the ADNs seen in the WT prior to their section was dependent on the presence of ASIC2. We then tested the central mediation of the BR by electrically stimulating ADN and recording the reflex decreases in heart rate (HR) and BP. As seen below, the centrally mediated activation of the BR was similar in the ASIC2 KO (n=9) and WT (n=7) mice. Responses to ADN stim. WT ASIC2−/− ΔHR (beats/min) 10 Hz −16.9±2.5 −16.1±2.4 20 Hz −52.8±10.8 −45.2±5.9 30 Hz −81.3±15.9 −81.1±11.6 ΔBP (mmHg) 10 Hz −5.6±2.4 −8.7±3.3 20 Hz −17.5±4.5 −19.1±5.7 30 Hz −26.4±5.4 −30.1±5.5 We conclude that ASIC2 is an essential determinant of the arterial baroreflex primarily by virtue of its contribution to mechanosensitivity of the arterial baroreceptors and not by altering the central mediation of the baroreflex. This work was supported by NIH grant HL14388

Baroreflexes of the rat. VI. Sleep and responses to aortic nerve stimulation in the dmNTS

The sensitivity of the baroreflex determines its stability and effectiveness in controlling blood pressure (BP). Sleep and arousal are reported to affect baroreflex sensitivity, but the findings are not consistent across studies. After statistically correcting the effect of sleep on the baselines in chronically neuromuscular-blocked (NMB) rats, we found that sleep affects BP and heart period (HP) baroreflex gain similarly. This finding is consistent with baroreflex modulation of HP and BP before divergence of the sympathetic and parasympathetic pathways. Therefore, we hypothesized that the gain modulation occurs in the dorsal medial nucleus of the solitary tract (dmNTS). The present study used long-term dmNTS recordings in NMB rats and single-pulse aortic depressor nerve stimulation. Under these conditions, the magnitude of A-fiber evoked responses (ERs), recorded from second- or higher-order dmNTS baroreflex neurons, was reliably augmented during high-amplitude low-frequency EEG activity (slow-wave sleep) and reduced during low-amplitude high-frequency EEG activity (arousal; DeltaER = 11%, t = 9.49, P < 0.001, degrees of freedom = 1,016). This result has methodological implications for techniques that use changes in HP to estimate baroreflex BP gain and general implications for understanding the relationship between sleep and cardiovascular control.

Evidence that blood pressure remains under the control of arterial baroreceptors in renal hypertensive rats

The purpose of the present study was to determine the range of the influence of the baroreflex on blood pressure in chronic renal hypertensive rats. Supramaximal electrical stimulation of the aortic depressor nerve and section of the baroreceptor nerves (sinoaortic denervation) were used to obtain a global analysis of the baroreceptor-sympathetic reflex in normotensive control and in chronic (2 months) 1-kidney, 1-clip hypertensive rats. The fall in blood pressure produced by electrical baroreceptor stimulation was greater in renal hypertensive rats than in normotensive controls (right nerve: -47 +/- 8 vs -23 +/- 4 mmHg; left nerve: -51 +/- 7 vs -30 +/- 4 mmHg; and both right and left nerves: -50 +/- 8 vs -30 +/- 4 mmHg; P < 0.05). Furthermore, the increase in blood pressure level produced by baroreceptor denervation in chronic renal hypertensive rats was similar to that observed in control animals 2-5 h (control: 163 +/- 5 vs 121 +/- 1 mmHg; 1K-1C: 203 +/- 7 vs 170 +/- 5 mmHg; P < 0.05) and 24 h (control: 149 +/- 3 vs 121 +/- 1 mmHg; 1K-1C: 198 +/- 8 vs 170 +/- 5 mmHg; P < 0.05) after sinoaortic denervation. Taken together, these data indicate that the central and peripheral components of the baroreflex are acting efficiently at higher arterial pressure in renal hypertensive rats when the aortic nerve is maximally stimulated or the activity is abolished.

Chronic aortic denervation decreases anxiety and impairs social memory in rats

Aims The present study investigates anxiety-like behaviour and social cognitive performance in rats with chronic aortic denervation. Main methods The aortic depressor nerve was bilaterally transected in Wistar rats, causing an almost complete disruption of baroreceptors. Bilateral aortic denervated (bAD), sham-operated (SHAM), and intact (CTRL) rats performed an elevated plus-maze test and an olfactory social memory test, one and three months after operation. Blood pressure and heart rate were monitored in all animals. Key findings Systolic blood pressure, blood pressure lability and heart rate were elevated in bAD rats compared to SHAM and CTRL rats. In the elevated plus-maze test, bAD rats spent clearly more time in investigating open arms and performed more open arm entries than SHAM and CTRL rats during both testing sessions. The olfactory social memory test revealed that acquisition time during first contact with a juvenile rat did not differ between the groups of rats. The recognition time spent by SHAM and CTRL group of rats was distinctly decreased in comparison to the acquisition time, an indication of social memory. bAD rats investigated the juvenile rat during the second contact to a similar extent than during the first contact, both one and three months after denervation. Significance These results suggest that bilateral aortic denervation induces chronic neurogenic hypertension and elevated blood pressure lability, decreases anxiety-like behaviour and deteriorates social memory in rats while acquiring of social information is not affected.

S7.2 Altered autonomic control of cardiovascular function in obesity: Insights from obese Zucker rats

Human obesity is associated with the development of hypertension and exaggerated cardiovascular responses to stress. Underlying these attributes are elevated sympathetic nerve activity (SNA) and impaired baroreflexes. To begin to determine mechanisms underlying obesity-associated deficits in autonomic control we studied obese Zucker rats (OZR), which are hyperphagic due to a mutated leptin receptor. Compared to lean Zucker rats (LZR), which have functional leptin receptors, the OZR become obese shortly after weaning and develop autonomic deficits as they approach adulthood. Adult OZR have elevated arterial pressure (AP) and SNA compared to LZR. In addition, OZR have exaggerated sympatho-excitatory responses (somatic and diving reflexes) but blunted sympathetic baroreflexes compared to LZR. The following studies were performed in adult OZR and LZR (14–16 wks old) that were anesthetized with urethane (1.7 g/kg LZR weight, iv), ventilated, and paralyzed. Direct recordings of baroreceptor afferent nerve activity (aortic depressor nerve, ADN) showed that ADN responses to evoked changes in AP were comparable in OZR and LZR. In contrast, electrical stimulation of the ADN evoked blunted inhibitions of SNA and AP in OZR compared to LZR. This deficit appears to extend to other sympatho-inhibitory reflexes initiated by the vagus nerve, because stimulation of the vagal afferents (electrical or by iv injection of phenybiguanide, 1–16 µg) elicited smaller decreases in SNA in OZR compared to LZR. These data suggest that impaired baroreflexes in OZR are not due to the ability to sense changes in AP, but altered central mechanisms that regulate SNA.

Aortic baroreceptor function and depressed baroreflex sensitivity following myocardial infarction

Depressed sinoaortic baroreflex control of heart rate following myocardial infarction (MI) is associated with increased morbidity and mortality. The etiology of this autonomic disturbance is unknown but could potentially occur at several levels of the reflex arc. The purpose of this study was to assess whether depressed baroreflex sensitivity (BRS) post-MI is associated with aortic baroreceptor dysfunction.BRS was measured before and 4–8 weeks after anterior MI in 17 chronically-instrumented, trained, conscious dogs. BRS (ms/mm Hg) was defined as the slope of the relationship between changes in systolic blood pressure (SBP) and heart period in response to a bolus dose of phenylephrine (PE). After the effects of MI on BRS were determined, the animals were anesthetized and the aortic depressor nerves (ADN) were isolated from the cervical vagi. Aortic baroreceptor function was measured by direct recording of ADN activity during gradual elevation of SBP induced by PE infusion.BRS was depressed following MI in 7 of these dogs and preserved in the remaining 10. Aortic baroreceptor sensitivity (ABS) defined as the slope of the relationship between changes in ADN activity and SBP was not significantly different between the dogs with depressed BRS compared to the dogs with preserved BRS post-MI.In conclusion, the response of the aortic baroreceptors to an increase in SBP is similar in dogs with and without depressed BRS post-MI. Based on these data, we conclude that depressed reflex control of heart rate following MI is not related to dysfunction of the afferent limb of the sinoaortic baroreflex.

Impaired Baroreflex Control of Renal Sympathetic Nerve Activity (RSNA) and Elevated Basal RSNA in Type 1 Diabetic Mice (OVE26)

To investigate the effects of chronic diabetes on baroreflex control of renal sympathetic nerve activity (RSNA) and basal RSNA, OVE26 diabetic (transgenic mouse line which develops hyperglycemia within the first three weeks after birth) and FVB control mice 5‐6 months old were studied. Under anesthesia, RSNA in response to sodium nitroprusside (SNP) ‐ and phenylephrine (PE)‐induced mean arterial pressure changes (ΔMAP) were measured. Baroreflex‐induced inhibition of RSNA during PE infusion was characterized using the sigmoid logistic function curve. Baroreflex‐induced excitation of RSNA during SNP infusion was characterized by the RSNA vs. ΔMAP relationship. MAP responses to the left aortic depressor nerve (ADN) stimulation were evaluated. Basal RSNA was estimated as the resting RSNA divided by the maximal RSNA measured during SNP‐infusion. Compared to FVB control, we found in OVE26 mice that (1) RSNA in response to MAP increase during PE infusion was dramatically reduced, as characterized by the maximal gain of the RSNA sigmoid logistic function curve (FVB: ‐20.0 ± 5.1; OVE26: ‐7.6 ± 0.8 %/mmHg, p&lt;0.05); (2) RSNA in response to MAP decrease during SNP infusion was also attenuated (p&lt;0.05); (3) MAP responses to ADN stimulation were reduced (p&lt;0.05); (4) the basal RSNA was elevated (P&lt;0.05). We concluded that chronic diabetes impairs baroreflex control of RSNA and elevates basal RSNA in OVE26 diabetic mice. The use of the transgenic OVE26 diabetic mouse model may underlie a foundation for the further understanding of diabetes‐induced autonomic neuropathy. Supported by NIH HL79636.

Electrical stimulation of the aortic depressor nerve in conscious rats still causes a hypotensive effect after blockade of the autonomic nervous system and nitric oxide production

Previous observations indicated that α1 ‐ adrenergic receptor blockade did not blunt, completely, the hypotensive response to electrical stimulation of the aortic depressor nerve (ADN) in conscious normotensive and L‐NAME hypertensive rats. In the present study it was examined whether the reflex bradycardia played a role in the above hypotensive response. Rats received catheters into the femoral artery and vein and a pair of electrodes around the ADN under pentobarbital anesthesia. ADN stimulation (1mA, 2 ms, 5 to 90 Hz) was applied during 20s, before and after triple pharmacological blockade (prazosin + atropine + atenolol). The hypotensive response to ADN stimulation was greater in L‐NAME hypertensive (‐26±4 to ‐70±10 mmHg; N=6) as compared to normotensive (‐21±3 to ‐54±2 mmHg; N=8) rats, while the bradycardic responses were similar (‐40±12 to ‐147±39 bpm and ‐17±3 to ‐94±19 bpm). After the triple pharmacological blockade the bradycardic response was abolished. Nevertheless, the hypotensive response was not completely blunted and the significant remnant fall in mean arterial pressure was similar in normotensive (12±2 to 27±2 mmHg) and L‐NAME hypertensive rats (13±2 to 27±3 mmHg). These results show that the bradycardic response did not affect the residual fall in pressure induced by ADN stimulation and suggest the activation of a non‐adrenergic vasodilatory mechanism which does not involve nitric oxide.

Hydrogen Peroxide Mediates Post‐Excitatory Depression of Baroreceptor Afferent Activity in Vivo

Acute hypertension leads to 'post‐excitatory depression' (PED) of baroreceptor (BR) activity after the period of elevated blood pressure (BP), a phenomenon that contributes to BR resetting. The molecular mechanism of PED is not fully understood. We recently demonstrated that electrical stimulation of isolated BR neurons in vitro generates reactive oxygen species that cause PED of action potential firing after the period of neuronal activation (Hypertension 43(6):1349, 2004). In the present study, we tested the hypothesis that the reactive oxygen species hydrogen peroxide (H2O2) mediates BR PED in vivo. The left aortic depressor nerve (ADN) was draped over a recording/stimulating electrode and crushed centrally to prevent reflex changes in BP in anesthetized C57BL/6 mice. Afferent ADN (BR) activity was recorded before and after a brief period of ADN stimulation (3V, 2ms pulses at 20Hz for 10s). Afferent BR activity was markedly inhibited after the 10s period of electrical stimulation, averaging 50±5% and 80±8% of baseline levels 5 and 60s after the stimulation was terminated (n=7). This PED was abolished after administration of the membrane permeable H2O2 scavenger PEG‐catalase (4000 U, IV) with activity averaging 100±4 and 126±7% of baseline 5 and 60s after ADN stimulation (n=7). PED was unaffected by administration of the saline vehicle in a separate group of mice (n=6). We conclude that H2O2 generated during activation of BR afferents causes PED. This autocrine‐feedback inhibition of BR activity may contribute to rapid BR resetting in acute hypertension. (HL14388, VA)

Impaired baroreflex control of renal sympathetic nerve activity in type 1 diabetic mice (OVE26)

To investigate the effects of chronic diabetes on baroreflex control of renal sympathetic nerve activity (RSNA), OVE26 diabetic (transgenic mouse line which develops hyperglycemia within the first 3 weeks after birth) and FVB control mice 5–6 months old were studied. Under anesthesia, RSNA in response to sodium nitroprusside (SNP)– and phenylephrine (PE)-induced mean arterial pressure changes (ΔMAP) were measured. Baroreflex-induced inhibition of RSNA during PE infusion was characterized using the sigmoid logistic function curve. Baroreflex-induced excitation of RSNA during SNP infusion was characterized by the RSNA vs. ΔMAP relationship. Mean arterial pressure (MAP) responses to the left aortic depressor nerve (ADN) stimulation were evaluated. Compared to FVB control, we found in OVE26 mice that (1) RSNA in response to MAP increase during PE infusion was dramatically reduced, as characterized by the maximal gain of the RSNA sigmoid logistic function curve (FVB: −20.0±5.1; OVE26: −7.6±0.8%/mm Hg, P<0.05); (2) RSNA in response to MAP decrease during SNP infusion was also attenuated ( P<0.05); (3) MAP responses to ADN stimulation were reduced ( P<0.05). We concluded that chronic diabetes impairs baroreflex control of RSNA in OVE26 diabetic mice. The use of the transgenic OVE26 diabetic mouse model may underlie a foundation for the further understanding of diabetes-induced autonomic neuropathy.

The dmNTS is not the source of increased blood pressure variability in baroreflex denervated rats

A consistent and prominent feature, observed across many species, including our neuromuscular blocked (NMB) rat preparation, is that obliterating the baroafferent inputs to the brainstem, e.g., by sinoaortic denervation (SAD), significantly increases blood pressure variability (BPV). The sources of the BPV, however, are not completely understood, but involve both the central and the peripheral mechanisms. The key central noise source is likely in the brainstem. Previously, in NMB rats, we showed that the maximum gain of the baroreflex system is in the very low frequency (VLF) range of 0.01–0.2 Hz. In this study, using the same NMB preparation, we demonstrated that, after SAD, there was a significant increase in the VLF power of the expiratory systolic blood pressure (EsBP) spectrum, but a decrease in the VLF power of the expiratory heart inter-beat-interval (EIBI) spectrum. Because dmNTS is the only major common anatomic node for the vascular sympathetic and the cardiac parasympathetic pathways, the opposite changes in the post-SAD VLF powers of the EsBP and EIBI spectra suggest that dmNTS is unlikely the major noise source for the post-SAD BPV. Supporting this finding, we found that the dmNTS evoked response to single pulse baroreflex afferent aortic depressor nerve (ADN) stimuli was substantially more reliable than the evoked systolic blood pressure responses to the same stimuli.

Effects of baroreceptor activation on respiratory variability in rat

Controversy surrounds the respiratory responses to baroreceptor activation. Although many reflexes that effect respiration (e.g. chemoreflexes and nociceptive reflexes) frequently affect cardiovascular parameters, the effect of baroreflex stimulation within normal physiological limits is generally considered to affect only blood pressure and heart rate. Even though previous authors have reported that baroreceptor activation can affect respiratory activity, the effects on respiratory frequency and amplitude are highly variable, and changes in perfusion evoked by blood pressure manipulation could account for the observed effects. Here, we determined the respiratory effects of activating arterial baroreceptors by intravenous injection of phenylephrine or angiotensin II, or by electrical stimulation of the aortic depressor nerve (ADN). In urethane-anesthetized vagotomized rats, 1, 2 and 4s trains of tetanic ADN stimulation evoked 3.1+/-1.1%, 11.2+/-13.6% and 21.9+/-8.9% increases in inspiratory (TI) time and 26.5+/-18%, 23.4+/-15.7% and 34.6+/-20.9% increases in expiratory (TE) time, respectively (P<0.05 in both cases), but no effect on the amplitude of bursts recorded in the phrenic nerve. Similar effects were observed following pressor trials evoked by intravenous PE (TE: +26.1+/-9.1%, P<0.01), but not Ang II. Intermittent ADN stimulation (single pulse, 1 Hz) significantly increased the variability of TI during periods of low respiratory drive (P<0.05) without significantly affecting any other parameters. We propose that a specific baroreceptor-respiratory response exists that is independent of changes in blood flow. In contrast to the effects of baroreceptor stimulation on sympathetic nerve activity, the baro-respiratory response is subtle and highly dependent on respiratory drive.

Vestibular control of arterial blood pressure during head-down postural change in anesthetized rabbits

This study was undertaken to elucidate neural control of the arterial blood pressure (ABP) in head-down postural change which causes both stimulation to the vestibular system and head-ward fluid shift. Experiments were carried out with urethane-anesthetized rabbits. The animal was mounted on a tilting table, tilted to 45 degrees head-down in 5 s, and kept at the position for 5 min. The head-down rotation (HDR) induced a transient decrease in ABP (10 +/- 3 mmHg; mean +/- SE), and then the pressure gradually recovered toward the pre-HDR level during the 5 min at the head-down position. Pretreatment with hexamethonium bromide, a ganglionic transmission blocker, suppressed the HDR-induced drop of ABP, suggesting that the ABP drop was induced by an inhibition of autonomic neural outflows. Renal sympathetic nerve activity (RSNA) decreased considerably after 1.6 +/- 0.2 s from the onset of HDR, which was followed by the ABP drop. Aortic depressor nerve activity (ADNA), an afferent for baroreceptor reflex, increased significantly during the rotation, but the peak of ADNA increase was 3.2 +/- 0.5 s after the initiation of the HDR. Therefore, the suppression of RSNA seems to be induced mainly by a quicker mechanism than baroreceptor reflex. In order to test the possibility, we examined changes in ABP and RSNA during HDR using vestibular-lesioned rabbits. In these rabbits, RSNA and ABP did not change significantly during HDR. These results suggest that vestibular organs play a role in the transient drop in ABP induced by HDR through the suppression of sympathetic nerve outflows.

Local anaesthetics for acute reversible blockade of the sympathetic baroreceptor reflex in the rat

Sinoaortic denervation is a common method used in the investigation of function in the cardiovascular system. In the rat, this is usually accomplished by transection of the carotid sinus and aortic depressor nerves, which is permanent. We propose a novel, and simple method for acute baroreceptor denervation in the rat in which the region around the carotid sinuses is superfused with local anaesthetic agents. We demonstrate that complete baroreceptor denervation can be achieved for longer (bupivacaine, 30–60 min) or shorter (lignocaine, 10–30 min) periods, without harming the physiological state of the rat.

Galanin microinjection into rostral ventrolateral medulla of the rat is hypotensive and attenuates sympathetic chemoreflex

Galanin is present in neurons in the brain that are important in the control of arterial pressure, and intracisternal administration of galanin evokes hypotension, but the site of action is unknown. In urethane-anesthetized, vagotomized mechanically ventilated Sprague-Dawley rats (n = 34), we investigated the effects of microinjecting galanin (1 mM, 50 nl, 50 pmol) into the rostral ventrolateral medulla on resting splanchnic sympathetic nerve activity, arterial pressure, heart rate, and phrenic nerve activity. Second, we determined the effect of microinjecting galanin into the rostral ventrolateral medulla on the cardiovascular response to stimulation of central and peripheral chemoreceptors, arterial baroreceptors, and the somatosympathetic reflex. Galanin caused a prolonged reduction in resting splanchnic sympathetic nerve activity (-37.0 +/- 7.2% of baseline), mean arterial pressure (-17.0 +/- 3.5 mmHg), and heart rate (-25.0 +/- 9.1 beats/min). Galanin increased the sympathoinhibitory response to aortic depressor nerve stimulation by 51.8%, had no effect on the somatosympathetic reflex, and markedly attenuated the effect of hypercapnia and hypoxia on arterial pressure (by 65% and 92.4% of control, respectively). These results suggest a role for galanin neurotransmission in the integration of the cardiovascular responses to hypoxia, hypercapnia, and the sympathetic baroreflex in the rostral ventrolateral medulla. The data suggest that galanin may be an important peptide in the homeostatic regulation of chemosensory reflexes.

Acute and chronic electrical activation of baroreceptor afferents in awake and anesthetized subjects

Electrical stimulation of baroreceptor afferents was used in the 1960's in several species, including human beings, for the treatment of refractory hypertension. This approach bypasses the site of baroreceptor mechanosensory transduction. Chronic electrical stimulation of arterial baroreceptors, particularly of the carotid sinus nerve (Hering's nerve), was proposed as an ultimate effort to treat refractory hypertension and angina pectoris due to the limited nature of pharmacological therapy available at that time. Nevertheless, this approach was abandoned in the early 1970's due to technical limitations of implantable devices and to the development of better-tolerated antihypertensive medications. More recently, our laboratory developed the technique of electrical stimulation of the aortic depressor nerve in conscious rats, enabling access to hemodynamic responses without the undesirable effect of anesthesia. In addition, electrical stimulation of the aortic depressor nerve allows assessment of the hemodynamic responses and the sympathovagal balance of the heart in hypertensive rats, which exhibit a well-known decrease in baroreflex sensitivity, usually attributed to baroreceptor ending dysfunction. Recently, there has been renewed interest in using electrical stimulation of the carotid sinus, but not the carotid sinus nerve, to lower blood pressure in conscious hypertensive dogs as well as in hypertensive patients. Notably, previous undesirable technical outcomes associated with electrical stimulation of the carotid sinus nerve observed in the 1960's and 1970's have been overcome. Furthermore, promising data have been recently reported from clinical trials that evaluated the efficacy of carotid sinus stimulation in hypertensive patients with drug resistant hypertension.