Sinoaortic-denervated Rats Research Articles

Participation of arterial baroreceptors input and peripheral vasopressin in the suppression of renal sympathetic nerve activity induced by central salt loading in conscious rats

We examined whether renal sympathetic nerve activity (RSNA) is suppressed in response to intracerebroventricular (i.c.v.) administration of hypertonic saline (HS) in conscious rats. RSNA was suppressed by i.c.v. administration of HS (0.3 M, 0.67 M, and 1.0 M, 1 μl/min for 20 min) in a concentration-dependent manner, which was attenuated under pentobarbital anesthesia. To elucidate mechanisms responsible for central HS-induced decrease in RSNA, possible involvement of arterial baroreceptors and peripheral arginine vasopressin (AVP) secreted from the posterior pituitary gland was examined using sinoaortic denervated (SAD) rats and non-peptide vasopressin receptor antagonists. The maximum suppression of RSNA (−81.5±5.5%) in control rats was significantly attenuated to −32.5±6.7% in SAD rats and to −55.8±5.7% in rats pretreated with intravenous vasopressin V 1 receptor antagonist, OPC-21268 (5 mg/kg, i.v.). However, in SAD rats, pretreatment with vasopressin V 1 receptor antagonist did not further affect the RSNA inhibition induced by central salt loading. The results suggest that the suppression of RSNA during central salt loading is mainly dependent on the arterial baroreceptors input and the `additive' role of peripheral vasopressin.

Contribution of baroreceptors and chemoreceptors to ventricular hypertrophy produced by sino-aortic denervation in rats.

1. To test whether sino-aortic denervation (SAD)-induced right ventricular hypertrophy (RVH) is a consequence of baroreceptor or chemoreceptor denervation, we compared the effects of aortic denervation (AD), carotid denervation (CD), SAD and a SAD procedure modified to spare the carotid chemoreceptors (mSAD), 6 weeks after denervation surgery in rats. A sham surgery group served as the control. 2. The blood pressure (BP) level was unaffected by AD, CD or SAD, but increased (9 %) following mSAD. The mean heart rate level was not affected. Short-term BP variability was elevated following AD (81 %), SAD (144 %) and mSAD (146 %), but not after CD. Baroreflex heart rate responses to phenylephrine were attenuated in all denervation groups. 3. Significant RVH occurred only following CD and SAD. These procedures also produced high mortality (CD and SAD) and significant increases in right ventricular pressures and haematocrit (CD). 4. Significant left ventricular hypertrophy occurred following CD, SAD and mSAD. Normalized left ventricular weight was significantly correlated with indices of BP variability. 5. These results suggest that SAD-induced RVH is a consequence of chemoreceptor, not baroreceptor, denervation. Our results also demonstrate that a mSAD procedure designed to spare the carotid chemoreceptors produced profound baroreflex dysfunction and significant left, but not right, ventricular hypertrophy.

Sino-aortic denervation augments the increase in blood pressure seen during paradoxical sleep in the rat.

Using a computer assisted telemetric system, we have re-examined the effect of sino-aortic denervation (SAD) on the changes in arterial blood pressure (AP) and heart rate (HR) during sleep in the rat suitably recovered from the operation. Eight 1 hourly polygraphic recordings were performed 4 weeks after the initial SAD surgery. In the SAD rats, the increase in AP during paradoxical sleep (PS) was much larger than that in sham-operated rats. HR in the SAD rats increased on-going from slow-wave sleep to PS, but it showed no change in sham-operated rats. The present study suggests that chronic SAD causes the enhanced AP increase during PS concomitantly with the persistent hypertension and tachycardia across sleep-wake states.

Quantitative relationship between fluctuations of blood pressure and sympathetic nerve activity in pentobarbital anesthetized rats

Transfer function analysis was used to examine the coupling between the sympathetic nerve activity (SNA) and the blood pressure (BP) fluctuations. In pentobarbital anesthetized Wistar rats, linear regression of the relationship between frequency (X-axis) and the logarithmic transfer magnitude, i.e. log (BP power density/renal SNA power density) (Y-axis), in the low frequency range (0.016–0.85 Hz) revealed an excellent fit ( r=0.97–0.98). Comparing the regression lines, rats under large dose of pentobarbital anesthesia (40 mg/kg, i.v. single dose) had significantly smaller intercept and slope values compared to rats under small dose of pentobarbital anesthesia (12.5 mg/kg). When intercept and slope values were compared between intact and acutely sinoaortic denervated rats, no significant difference were found. The results suggest that sympathetic modulation of vasomotor tone may be a major factor in generating BP fluctuations between 0.016 and 0.85 Hz in rats. Furthermore, these results support the possibility of using low frequency spectral power of BP to quantitatively estimate the fluctuations of SNA for rats under pentobarbital anesthesia if anesthetic depth is controlled.

Adrenoceptor Involvement in the Cardiovascular Responses to B-HT 920 in Sinoaortic Denervated Rats

1. A study was made relating the involvement of α-adrenoceptors in the cardiovascular responses to intracerebroventricular (ICV) injection of B-HT 920, a clonidine-type drug, in conscious sham-operated and sinoaortic-denervated rats. 2. Wistar rats were used, 7 days after the sham operation or sinoaortic denervation. For ICV injection of drugs, a guide cannula had been previously implanted in the left lateral ventricle. 3. In sham-operated rats, cardiovascular responses to B-HT 920 (10–60 μg) were increased blood pressure and bradycardia; but, in sinoaortic-denervated rats, after the pressor response, a decrease in blood pressure also was seen. The responses to this agent were greater in sinoaortic-denervated rats than in sham-operated animals. Treatment with the α 2-adrenoceptor antagonist yohimbine (30 μg), the imidazoline receptor antagonist idazoxan (15 μg) and the α 1A-adrenoceptor antagonist 5-methylurapidil (15 μg) blocked the responses to B-HT 920 (30 μg). The α 1-adrenoceptor antagonist prazosin (15 μg) and the α 1B-adrenoceptor antagonist chloroethylclonidine (100 μg) did not modify the responses to agonist. 4. Sinoaortic denervation enhances the cardiovascular responses to B-HT 920. Moreover, the effects of ICV administration of B-HT 920 could be mediated by several types of brain receptors: imidazoline receptors and α 1A- and α 2-adrenoceptors.

Muscarinic Receptor Subtype Involvement in Brain Cholinergic Stimulation by Intracerebroventricular Neostigmine in Sinoaortic Denervated Rats

1. The present studies evaluated the participation of central muscarinic receptors in the cardiovascular effects of centrally injected neostigmine, a quaternary anticholinesterase, in conscious, sham-operated rats and in sinoaortic denervated animals. 2. The dose-dependent pressor effect of neostigmine (0.1 to 1 μg ICV) was greater in sinoaortic denervated rats than in sham-operated animals, but only a dose-dependent bradycardic effect was seen in sham-operated rats. 3. Doses of 3.3 nmol (ICV) of both the M 1 muscarinic antagonist, pirenzepine, and the M 3 muscarinic antagonist, 4-DAMP, prevented the pressor response to 1 μg of neostigmine in sham-operated rats and in sinoaortic denervated animals; however, the M 2 muscarinic antagonist, AF-DX116, partially blocked this response in sham-operated rats while failing to do so in sinoaortic denervated rats. In sham rats, doses of 3.3 nmol (ICV) of both pirenzepine and 4-DAMP prevented the bradycardic response to 1 μg (ICV) of neostigmine, whereas AF-DX116 induced a partial blockade. 4. 4-DAMP, at the dose of 0.3 nmol (ICV), but not pirenzepine at the same dose, prevented the pressor effect of neostigmine (0.1 to 1 μg ICV) in both groups of rats. Both muscarinic antagonists at this dose prevented the bradycardia elicited by the anticholinesterase (0.1 to 1 μg ICV), but 4-DAMP showed a greater antagonistic action on this cardiac effect than pirenzepine. In sham-operated rats, ICV injection of 0.3 nmol of AF-DX116 failed to modify the cardiovascular responses to 0.3 μg of neostigmine. 5. Results suggest mainly an involvement of brain M 3-subtype muscarinic receptors in the cardiovascular effect of intracerebroventricular administration of anticholinesterase neostigmine in both groups of rats.

Influence of sino-aortic barodenervation on the cardiovascular effects of imidazoline-like drugs

Earlier findings have shown that hypotensive effects of centrally acting drugs, such as clonidine, are enhanced in animals after denervation of arterial baroreceptors. The purpose of this study was to investigate the dynamic of changes in arterial pressure, heart rate and hypotensive effects of clonidine, rilmenidine and moxonidine in Wistar rats after sino-aortic denervation (SAD) using radio-telemetry. SAD was followed by significant elevation of arterial pressure lability (the standard deviation of the mean arterial pressure), while the baseline mean arterial pressure (MAP) and heart rate in barodenervated rats (12 days after SAD) was similar to intact rats. The hypotension produced by clonidine, rilmenidine and moxonidine was much greater in SAD rats than in intact rats. The study suggests that baroreflex mechanisms are not only important for maintaining levels of blood pressure in the very short term, but also for buffering the effects of centrally acting antihypertensive drugs.

Baroreflex control of sympathetic activity in experimental hypertension.

The arterial baroreceptor reflex system is one of the most powerful and rapidly acting mechanisms for controlling arterial pressure. The purpose of the present review is to discuss data relating sympathetic activity to the baroreflex control of arterial pressure in two different experimental models: neurogenic hypertension by sinoaortic denervation (SAD) and high-renin hypertension by total aortic ligation between the renal arteries in the rat. SAD depresses baroreflex regulation of renal sympathetic activity in both the acute and chronic phases. However, increased sympathetic activity (100%) was found only in the acute phase of sinoaortic denervation. In the chronic phase of SAD average discharge normalized but the pattern of discharges was different from that found in controls. High-renin hypertensive rats showed overactivity of the renin angiotensin system and a great depression of the baroreflexes, comparable to the depression observed in chronic sinoaortic denervated rats. However, there were no differences in the average tonic sympathetic activity or changes in the pattern of discharges in high-renin rats. We suggest that the difference in the pattern of discharges may contribute to the increase in arterial pressure lability observed in chronic sinoaortic denervated rats.

Effect of sinoaortic denervation on arterial pressure changes evoked by bed nucleus stimulation

To assess whether evoked changes in arterial pressure after stimulation of the bed nucleus of the stria terminalis (BST) are opposed by baroreceptor input to the central nervous system, the rostral BST of sinoaortic-denervated (SAD), urethane- (1.3 g/kg) anesthetized, male Sprague-Dawley rats was probed for cardiovascular reactive sites. Electrical stimuli (50 μA, 50 Hz), delivered through stereotaxically placed glass semimicroelectrodes, were directed to the rostral medial BST. Sham-operated animals served as controls. Stimulation sites were correlated with cytoarchitecturally distinct areas within the rostral BST, and changes in mean arterial pressure (MAP) were subjected to statistical analysis. Consistent with our previous observations, stimulation of the rostral BST produced changes ( p < 0.05) in MAP in both sham-operated and SAD rats. Medial stimulation produced pressor responses; lateral stimulation produced depressor responses. In contrast, neither the magnitude nor the duration of the stimulation-evoked changes in MAP were affected by SAD. Thus, in the urethane-anesthetized rat, the rostral medial BST influence on cardiovascular function is not affected by changes in baroreceptor activity.

Influence of arterial baroreceptors and intracerebroventricular guanabenz on synchronized renal nerve activity.

The contributions of changes in the number of active fibres and the peak interval of synchronized neural discharges to arterial baroreflex regulated alterations in renal sympathetic nerve activity were examined in intact conscious rats. Stimulation of central nervous system alpha 2 adrenoreceptors with intracerebroventricular guanabenz (10, 20, 40 micrograms) was used to alter renal sympathetic nerve activity by a non-reflex mechanism in both intact and sinoaortic denervated (SAD) rats. Synchronized renal sympathetic nerve discharge was analysed with the sympathetic peak detection algorithm. When arterial pressure was increased from 50 mmHg to 150 mmHg in intact rats, the peak height (number of simultaneously active fibres) of synchronized discharges decreased in a sigmoidal fashion while the peak interval remained unchanged. Guanabenz produced a dose dependent inhibition of renal sympathetic nerve activity due to both a decrease in peak height and an increase in peak interval of synchronized discharges in both intact and SAD rats. Arterial baroreflex mediated changes in renal sympathetic nerve activity are due to changes in the number of simultaneously active nerve fibres. Central nervous system alpha 2 adrenoreceptor stimulation decreases renal sympathetic nerve activity by decreasing the number of active fibres and increasing the peak interval, acting on additional neural pathways not involved in buffering acute arterial pressure changes.

Effort voluntary control in diagnosis and treatment of Parkinson's diseases

Recent lines of inquiry indicate that sedatives can influence the immune system, leading to the concept of sedative-induced immunomodulation. It has been hypothesized that sedatives may alter immune responses by modulating the sympathetic nervous system, however, little information is known regarding the effects of sedatives on regulation of splenic sympathetic nerve discharge (SND), a significant omission based on the functional role that changes in splenic SND exert on splenic cytokine gene expression. The present investigation determined the effect of systemic Dexmedetomidine (Dex) administration on the level of directly-recorded splenic SND and tested the hypothesis that the intravenous administration of Dex would inhibit splenic SND in anesthetized rats. The present results demonstrate for the first time that intravenous Dex administration significantly reduces splenic sympathetic nerve outflow in baroreceptor-intact and sinoaortic-denervated rats, indicating that Dex administration alters the central regulation of splenic SND. The present results provide new information regarding the effect of a centrally-acting alpha2-adrenergic agonist on the level of sympathetic nerve outflow to a secondary lymphoid organ that plays a critical role in peripheral immune responses.

Intermittent hypoxia (IH) improves hypoxic ventilatory sensitivity and blood dopamine (DA) in patients with Parkinson's disease (PD)

Recent lines of inquiry indicate that sedatives can influence the immune system, leading to the concept of sedative-induced immunomodulation. It has been hypothesized that sedatives may alter immune responses by modulating the sympathetic nervous system, however, little information is known regarding the effects of sedatives on regulation of splenic sympathetic nerve discharge (SND), a significant omission based on the functional role that changes in splenic SND exert on splenic cytokine gene expression. The present investigation determined the effect of systemic Dexmedetomidine (Dex) administration on the level of directly-recorded splenic SND and tested the hypothesis that the intravenous administration of Dex would inhibit splenic SND in anesthetized rats. The present results demonstrate for the first time that intravenous Dex administration significantly reduces splenic sympathetic nerve outflow in baroreceptor-intact and sinoaortic-denervated rats, indicating that Dex administration alters the central regulation of splenic SND. The present results provide new information regarding the effect of a centrally-acting alpha2-adrenergic agonist on the level of sympathetic nerve outflow to a secondary lymphoid organ that plays a critical role in peripheral immune responses.

Central actions of adrenomedullin on cardiovascular parameters and sympathetic outflow in conscious rats.

Adrenomedullin (ADM) is reported to be a peripherally acting hypotensive peptide, but its central actions are unclear. We investigated the effects of centrally administered ADM on blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA) in conscious rats and sinoaortic-denervated (SAD) rats. We also investigated the receptors interacting with ADM using two putative antagonists. Intracerebroventricular administration of ADM in doses of 0.1 and 0.5 nmol/kg caused tachycardia and early inhibition of RSNA. Central ADM (1.0 nmol/kg) induced hypertension, tachycardia, and a decrease followed by an increase in RSNA. In SAD rats, increases in BP, HR, and RSNA at the late phase were enhanced by central ADM (1.0 nmol/kg), whereas the early decrease in RSNA remained. Thus the inhibition of RSNA via central ADM may be unrelated to the arterial baroreceptor reflex. Pretreatment with antagonists human calcitonin gene-related peptide-(8-37) and human ADM-(22-52) significantly suppressed the central actions of ADM. The findings suggest that ADM is involved as a neuropeptide in the receptor-mediated central regulation of the cardiovascular system and RSNA.

ANTICHOLINERGIC ACTION OF CLONIDINE IN RATS WITH SINOAORTIC DENERVATION

A study was carried out relating to the anticholinergic action of clonidine on the cardiovascular responses to i.c.v. injection of neostigmine, a quaternary anticholinesterase, in conscious sham-operated animals and rats with sinoaortic denervation, 7 days after the corresponding operation. Neostigmine (0.1–1 μg i.c.v.) induced a dose-dependent pressor and bradycardic responses in sham-operated rats but induced only an increase in blood pressure in sinoaortic-denervated animals. However, the pressor response in sinoaortic-denervated rats was significantly greater than in sham-operated animals. Clonidine (10 μg kg−1i.v.) induced a fall in mean arterial pressure in sinoaortic-denervated rats but not in sham-operated animals. Moreover, sinoaortic denervation reduced the bradycardic action of this antihypertensive drug. The anticholinesterase activity of clonidine (10 μg kg−1i.v.), given 30 min previously, prevented the bradycardic action of neostigmine (0.1–1 μg i.c.v.) but failed to modify the pressor effect in sham-operated rats. This α2-adrenergic agent reduced the pressor response to i.c.v. administration of neostigmine in sinoaortic-denervated rats. Alternatively, the i.c.v. administration of clonidine (3 μg i.c.v.), given either 15 or 30 min before neostigmine, only prevented the bradycardic effect of the anticholinesterase (0.3 μg i.c.v.) in sham-operated rats but not the pressor action of this drug. In sinoaortic denervated rats, 3 μg of clonidine i.c.v. reduced an increase in blood pressure by i.c.v. injection of the anticholinesterase. The results suggest different central cholinergic mechanisms and different cholinergic–adrenergic interactions on the cardiovascular responses elicited by centrally injected neostigmine in sinoaortic denervated rats.

Central activation by CS-932, a functionally relative M1 agonist

1.The present studies evaluated the participation of central muscarinic receptors in the cardiovascular effects of centrally injected neostigmine, a quaternary anticholinesterase, in conscious, sham-operated rats and in sinoaortic denervated animals.2.The dose-dependent pressor effect of neostigmine (0.1 to 1 μg ICV) was greater in sinoaortic denervated rats than in sham-operated animals, but only a dose-dependent bradycardic effect was seen in sham-operated rats.3.Doses of 3.3 nmol (ICV) of both the M1 muscarinic antagonist, pirenzepine, and the M3 muscarinic antagonist, 4-DAMP, prevented the pressor response to 1 μg of neostigmine in sham-operated rats and in sinoaortic denervated animals; however, the M2 muscarinic antagonist, AF-DX116, partially blocked this response in sham-operated rats while failing to do so in sinoaortic denervated rats. In sham rats, doses of 3.3 nmol (ICV) of both pirenzepine and 4-DAMP prevented the bradycardic response to 1 μg (ICV) of neostigmine, whereas AF-DX116 induced a partial blockade.4.4-DAMP, at the dose of 0.3 nmol (ICV), but not pirenzepine at the same dose, prevented the pressor effect of neostigmine (0.1 to 1 μg ICV) in both groups of rats. Both muscarinic antagonists at this dose prevented the bradycardia elicited by the anticholinesterase (0.1 to 1 μg ICV), but 4-DAMP showed a greater antagonistic action on this cardiac effect than pirenzepine. In sham-operated rats, ICV injection of 0.3 nmol of AF-DX116 failed to modify the cardiovascular responses to 0.3 μg of neostigmine.5.Results suggest mainly an involvement of brain M3-subtype muscarinic receptors in the cardiovascular effect of intracerebroventricular administration of anticholinesterase neostigmine in both groups of rats.

Sinoaortic denervation prevents postexercise reductions in arterial pressure and cardiac sympathetic tonus

Arterial pressure, cardiac sympathetic tonus (ST), and heart rate (HR) are reduced after a single bout of dynamic exercise in spontaneously hypertensive rats (SHR). To test if the arterial baroreflex is required for these postexercise responses, intact (n = 9) and sinoaortic-denervated (SAD) rats (n = 5) were chronically instrumented with an arterial catheter for the measurement of arterial pressure and HR and for the infusion of cardiac autonomic antagonists. Five days after instrumentation, cardiac ST and parasympathetic tonus (PT) were determined under two experimental conditions (no exercise and postexercise). SAD rats did not alter no-exercise cardiac ST (intact 47 +/- 3 vs. SAD 50 +/- 3 beats/min); however, no-exercise PT was reduced (intact -24 +/- 2 vs. SAD -4 +/- 4 beats/min, P < 0.05). Acute exercise reduced arterial pressure (postexertional hypotension, -20 +/- 3 mmHg, P < 0.05), cardiac ST (no exercise 47 +/- 3 vs. postexercise 24 +/- 3 beats/min, P < 0.05), and PT (no exercise -24 +/- 2 vs. postexercise -11 +/- 2 beats/min, P < 0.05) in intact SHR. In contrast, SAD prevented postexercise reductions in arterial pressure and cardiac ST (no exercise 50 +/- 3 vs. postexercise 59 +/- 7 beats/min). Furthermore, SAD had no effect on postexercise PT (no exercise -4 +/- 4 vs. postexercise -7 +/- 4 beats/min). These results demonstrate that the arterial baroreflex is required for the reduction in arterial pressure and cardiac ST that occurs in SHR after a single bout of dynamic exercise.

Influence of sympathetic blockade on the acute hypertensive response to aortic constriction.

The objective of the present study was to determine the contribution of the sympathetic nervous system to the hypertensive response to acute (45-min) aortic coarctation in conscious intact or sinoaortic-denervated (SAD) rats. Rats were treated chronically (5 wk) with guanethidine (50 mg.kg-1.day-1 i.p.) to induce sympathetic nerve degeneration or acutely with the alpha 1-adrenergic receptor antagonist prazosin. (1 mg/kg i.v.). Aortic constriction elicited a prompt and sustained rise in mean carotid pressure that was significantly greater in SAD than in intact rats. The increase in pressure was associated with reflex bradycardia only in the intact rats, whereas the heart rate of SAD rats did not change. Guanethidine treatment did not affect the arterial pressure or heart rate responses to aortic coarctation of intact rats but blunted the hypertensive response of SAD rats to the same values exhibited by intact rats. Prazosin administered 10 min after the beginning of aortic coarctation reduced the hypertensive response of SAD rats to the same level as that of intact rats. In conclusion, the data obtained by means of the association of sinoaortic deafferentation with chronic sympathectomy with guanethidine or acute alpha 1-adrenergic receptor blockade with prazosin indicate that the greater hypertensive response of SAD rats involves a lack of suppression of the sympathetic activity in the maintenance of the rise in pressure elicited by aortic coarctation.

Hemodynamic responses to acute aortic coarctation in conscious sinoaortic denervated rats.

The hemodynamic responses to acute (45 min) partial aortic constriction were studied in conscious intact (N = 7) or sinoaortic denervated (SAD) adult male Wistar rats (280-350 g, N = 7) implanted with carotid and femoral arterial catheters, a pneumatic cuff around the abdominal aorta and a pulsed Doppler flow probe to measure changes in aortic resistance. In addition, the hypertensive response and the reflex bradycardia elicited by total (N = 8) vs partial (N = 7) aortic constriction (monitored by maintenance of the pressure distal to the cuff at 50 mmHg) were compared in two other groups of intact rats. Intact rats presented a smaller hypertensive response (26 to 40% above basal level) to partial aortic constriction than SAD rats (38 to 58%). The calculated change in aortic resistance imposed by constriction of the aorta increased progressively only in intact rats, but was significantly smaller (193 to 306%) than that observed (501 to 591%) in SAD rats. Intact rats showed a significant bradycardia (23 to 26% change in basal heart rate) throughout coarctation, whereas the SAD rats did not (1 to 3%). Partial or total occlusion of the aorta induced similar hypertensive responses (37-38% vs 24-30% for total constriction) as well as reflex bradycardia (-15 to -17% vs -22 to -33%) despite a greater gradient in pressure (97-98 vs 129-140 mmHg) caused by total constriction. The present data indicate that the integrity of the baroreflex in intact rats can cause the hypertensive response to level off at a lower value than in SAD rats despite a progressive increase in aortic resistance. In addition, they also indicate that the degree of partial aortic constriction by maintenance of the pressure distal to the cuff at 50 mmHg already elicits a maximal stimulation of the arterial baroreflex.

Circadian rhythms of cardiovascular functions are modulated by the baroreflex and the autonomic nervous system in the rat.

We assessed the hypothesis that the baroreflex and the autonomic nervous system are important in the control of the circadian rhythms of cardiovascular functions. We continuously measured blood pressure (BP), heart rate (HR), and locomotor activity in sinoaortic denervated (SAD), sympathectomized, and atropine-injected rats by use of a radiotelemetry system. The circadian rhythm of mean blood pressure (MBP) was selectively disrupted in SAD rats under 12-hour light-dark (LD12:12) cycles as a result of an increase in MBP during the light period and disappeared under constant darkness (DD). The locomotor activity and HR were not remarkably affected by SAD. The circadian rhythm of MBP was suppressed in sympathectomized rats by a decrease in the MBP during the dark period, and the abrupt changes in MBP when the lighting was altered were not seen under LD. Under DD, an MBP rhythm similar to that observed under LD was obtained. Sympathectomized rats also showed lower HR levels during the dark period than intact rats under LD cycles. In atropine-injected rats, the MBP and HR increased, especially during the light period, resulting in a reduction of light-dark differences in MBP and HR. The locomotor activity showed an apparent 24-hour variation in the sympathectomized and atropine-injected rats. The disruption of the baroreflex selectively eliminates the circadian rhythm of BP, and the circadian rhythms of BP and HR are modulated by the autonomic nervous system in rats. The circadian rhythms of BP and HR are regulated by different mechanisms involving the autonomic nervous system.

Effect of carbon dioxide on autonomic cardiovascular responses to systemic hypoxia in conscious rats.

The contribution of the autonomic nervous system to the cardiovascular response to hypoxia with different levels of CO2 was investigated in conscious rats. Wistar rats were chronically instrumented for measurement of arterial blood pressure (ABP), electrocardiogram, and renal sympathetic nerve activity (RSNA). They were exposed to 1) hypocapnic hypoxia (Hypo), 2) isocapnic hypoxia (Iso), and 3) hypercapnic hypoxia (Hyper). Hypo caused a decrease in ABP, an increase in heart rate (HR) and RSNA, and a slight increase in plasma norepinephrine (NE). Iso caused no significant change in ABP or HR but did cause an increase in RSNA and plasma NE. Hyper caused an increase in ABP, a decrease in HR, and an increase in RSNA and plasma NE. In sinoaortic-denervated (SAD) rats, ABP and RSNA decreased and HR tended to decrease during Iso. SAD abolished the bradycardic response during Hyper. Atropine abolished the bradycardic response during Hyper, and HR tended to increase during all three kinds of hypoxia. In all three kinds of hypoxia, ABP and renal sympathetic nervous responses in atropine-treated rats were not significantly different from those in intact rats. These results indicate that Hypo causes sympathetic activation and parasympathetic inhibition while Iso and Hyper cause sympathetic and parasympathetic activation via peripheral chemoreceptors. The MABP-RSNA curve tended to shift to the left and the maximum gain of the baroreflex response tended to decrease during Hypo. In contrast, this curve shifted to the right and the maximum gain of the baroreflex response increased during Iso and Hyper, suggesting that baroreflex function is affected by arterial CO2 levels. We concluded that cardiovascular responses during hypoxia are modified by arterial Pco2 levels and mediated by the autonomic nervous system.