Differential effect of central command on aortic and carotid sinus baroreceptor-heart rate reflexes at the onset of spontaneous, fictive motor activity.

Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in conscious cats and spontaneous contraction in decerebrate cats. The purpose of this study was to examine whether central command attenuates the sensitivity of the carotid sinus baroreceptor-HR reflex at the onset of spontaneous, fictive motor activity in paralyzed, decerebrate cats. We confirmed that aortic nerve (AN)-stimulation-induced bradycardia was markedly blunted to 26 ± 4.4% of the control (21 ± 1.3 beats/min) at the onset of spontaneous motor activity. Although the baroreflex bradycardia by electrical stimulation of the carotid sinus nerve (CSN) was suppressed (P < 0.05) to 86 ± 5.6% of the control (38 ± 1.2 beats/min), the inhibitory effect of spontaneous motor activity was much weaker (P < 0.05) with CSN stimulation than with AN stimulation. The baroreflex bradycardia elicited by brief occlusion of the abdominal aorta was blunted to 36% of the control (36 ± 1.6 beats/min) during spontaneous motor activity, suggesting that central command is able to inhibit the cardiomotor sensitivity of arterial baroreflexes as the net effect. Mechanical stretch of the triceps surae muscle never affected the baroreflex bradycardia elicited by AN or CSN stimulation and by aortic occlusion, suggesting that muscle mechanoreflex did not modify the cardiomotor sensitivity of aortic and carotid sinus baroreflex. Since the inhibitory effect of central command on the carotid baroreflex pathway, associated with spontaneous motor activity, was much weaker compared with the aortic baroreflex pathway, it is concluded that central command does not force a generalized modulation on the whole pathways of arterial baroreflexes but provides selective inhibition for the cardiomotor component of the aortic baroreflex.

Dual tachycardias associating double-exit left aortic sinus cusp tachycardia with paroxysmal atrial fibrillation: evidence of a link between both arrhythmias by means of the autonomic nervous system.

INTRODUCTION: Dual tachycardias associating paroxysmal atrial fibrillation (AF) with double-exit left aortic sinus cusp tachycardia (LASCT) are described for the first time in a patient referred for AF ablation. CASE: Both tachycardias were successfully ablated under Carto-Merge guidance. Noteworthy, vagal denervation during AF ablation was responsible for an immediate decrease in LASCT occurrence and inducibility. CONCLUSION: This case highlights the critical role that the autonomic nervous system plays within the cardiac arrhythmia framework.

Differential contribution of aortic and carotid sinus baroreflexes to control of heart rate and renal sympathetic nerve activity.

We examined the roles of aortic and carotid sinus baroreceptors in control of heart rate (HR) and renal sympathetic nerve activity (RSNA) in 17 decerebrate rats. The baroreflex curves between the changes in mean arterial blood pressure (MAP) and HR or RSNA in response to intravenous injection of phenylephrine (10-20 µg/kg) or nitroprusside (10 µg/kg) were identified before and following sequential denervation of all four baroafferent nerves. The slope of the MAP-HR curve in the pressor range was decreased (P < 0.05) to 31 ± 7% of the control following denervation of bilateral aortic nerves, whereas it remained substantial (72 ± 10%) following denervation of bilateral carotid sinus nerves. The slope for HR became negligible following complete denervation of all four baroafferent nerves. In contrast, the slope of the MAP-RSNA curve decreased as the sequential baroafferent denervation progressed, irrespective of the denervation order, and it remained well as long as any single baroafferent nerve was intact. The similar influences of sequential baroafferent denervation on the responses of HR and RSNA were observed in the depressor range. Thus, it is likely that aortic and carotid sinus baroreceptors play differential roles in control of HR but they contribute similarly to control of RSNA.

NADPH oxidase contributes to the left ventricular dysfunction induced by sinoaortic denervation in rats.

The aim of this work was to investigate the role nicotinamide adenine dinucleotide phosphate (NADPH) oxidase on left ventricular dysfunction of rats submitted to sinoaortic denervation (SAD). Experiment 1: 8 weeks after SAD of rats, NADPH oxidase in left ventricles was assayed by Western blotting analysis. Experiment 2: Rats were subjected to SAD and received treatment with apocynin (an NADPH oxidase inhibitor, 30 mg/kg/day, intragastric administration) for 8 weeks; 8 weeks after SAD, Nox2 and Nox4 expressions and Rac1 activity of left ventricles were higher in SAD rats than those in sham-operated rats. Although treatment of SAD rats with apocynin did not affect blood pressure, blood pressure variability (BPV), and baroreflex function, it significantly attenuated left ventricular hypertrophy marked by reduced expression of atrial natriuretic factor and ß-myosin heavy chain. Treatment of SAD rats with apocynin abated oxidative stress marked by reduced malondialdehyde formation and suppressed nuclear factor-kappa B (NFκB) activation; inflammation marked by reduced monocyte chemoattractant protein-1 expression and myeloperoxidase activity; attenuated endoplasmic reticulum stress marked by reduced expression of CCAAT-enhancer-binding protein homologous protein, chaperone-glucose-regulated protein 78, and X-box protein 1; and alleviated cardiac fibrosis marked by reduced mRNA levels of collagens I and III and transforming growth factor beta. In conclusion, exaggerated BPV induces chronic myocardial oxidative stress and thereby aggravates cardiac remodeling in rats. These data suggest a potential role of NADPH oxidases in the pathogenesis of cardiac dysfunction induced by exaggerated BPV.

Continuous monitoring of arterial pressure indicates sinoaortic denervated rats are not hypertensive.

The mean arterial pressure (MAP) of nine sinoaortic denervated (SAD) and eight control rats housed in standard-sized metabolic cages was determined continuously via aortic cannulae and computerized data collection over 24 hours. These continuous measurements were compared with direct, mean aortic pressure measurements and indirect, tail-cuff systolic pressure determinations made while these rats were resting in a Lucite restrainer. Denervated rats were studied 1 month after debuffering. Both types of measurements made during restraint indicated that the SAD rats were hypertensive; the MAP averaged 145 +/- 3.4 mm Hg (mean +/- SEM) in SAD rats compared with 119 +/- 2.8 mm Hg in the control group (p less than 0.001), and the tail-cuff pressure in SAD rats was 156 +/- 5.4 vs 121 +/- 2.7 mm Hg in control rats (p less than 0.001). In contrast, continuous monitoring showed that the SAD rats were normotensive; the MAP averaged 119 +/- 4.7 mm Hg in the SAD group and 119 +/- 3.1 mm Hg in the control group. Denervation increased pressure lability; the average 24-hour standard deviation of MAP was 19.0 +/- 1.2 mm Hg in SAD rats vs 8.0 +/- 0.7 mm Hg in control rats (p less than 0.001). Apparently, arterial pressure is elevated during restraint in SAD rats because buffering by the baroreceptor reflex is absent, and pressure measurements made under these conditions give a false indication of hypertension.

Factors determining direct arterial pressure and its variability in hypertensive man.

Intra-arterial pressure was recorded continuously in 26 patients with uncomplicated essential hypertension under standardized conditions. Recordings were analyzed beat by beat to obtain mean pressures and variability, expressed as the standard deviation of the frequency histogram. The major factors influencing variability were the level of pressure and the intensity of physical activity; systolic variability increased with progressive impairment of sino-aortic baroreflexes. Diastolic pressure increased with the level of sympathetic activity as reflected by plasma norepinephrine levels. After allowance for the decrease of plasma renin activity (PRA) with age, direct relationships were observed between PRA (log values) and the level of pressure and systolic variability; plasma angiotensin II values did not correlate. Systolic variability increased with the systolic response to cold but was unrelated to the response to dynamic or isometric exercise. Variability also tended to increase with obesity and was unrelated to age, sex, or race.

Renal morphological changes after sinoaortic denervation in dogs.

The present study investigates morphological renal lesions in sinoaortic-denervated dogs 1 (n = 6) and 18 (n = 5) months after sinoaortic denervation compared with sham-operated controls (n = 8). After 1 month, a marked hyalinization and moderate thickening of the media of arterioles and small interlobular arteries were observed. These changes associated with edema and intimal thickening led to a narrowing of the lumen. In glomeruli, increase of mesangial matrix was focally present in all cases and associated with mesangial proliferation. In four of six cases, some glomeruli appeared retracted, with a large urinary space. A focal area of interstitial fibrosis occurred in just one case. After 18 months, similar but more pronounced vascular lesions were present, with marked hyperplasia of the media. Glomerular changes were characterized by mesangial lesions associated with focal glomerular sclerosis and thickening of Bowman's capsule. Tubulointerstitial lesions were more prominent in this group, with the presence of tubular epithelial changes and casts. Focal interstitial fibrosis, infiltrates, or both were demonstrated in all cases. These morphological lesions were associated with an increase in arterial blood pressure, proteinuria, and natriuresis and a decrease in urinary kallikrein. These results show that chronic sinoaortic denervation in dogs is associated with renal lesions similar to those observed in other well-established experimental and clinical hypertensive states.

Effect of sinoaortic deafferentation on renal wrap hypertension.

The purpose of this study was to determine whether sinoaortic deafferentation (SAD) alters the severity of hypertension or sympathoadrenal contribution to mean blood pressure (MAP) during renal wrap hypertension. Male Sprague-Dawley rats were implanted with radiotelemetry transmitters for 24-hour recording of MAP and heart rate. All rats underwent either SAD or sham SAD (Intact) surgery and were allowed to recover for 10 to 14 days. The rats were then assigned to a normotensive (Sham) group or a hypertensive (Wrap) group in which 1-kidney figure-8 renal wrap was performed. SAD increased the acute MAP response to renal wrap (Intact-Sham=5+/-1 mm Hg, Intact-Wrap=45+/-3 mm Hg, SAD-Sham=3+/-3 mm Hg, SAD-Wrap=58+/-4 mm Hg) and increased the lability of MAP (SD of MAP; Intact-Sham=3.8+/-0.2, Intact-Wrap=4.2+/-0.3, SAD-Sham=9. 6+/-1.4, SAD-Wrap=9.7+/-1.4). MAP was not different between SAD and Intact rats during 4 weeks after renal wrap or sham surgery; however, induction of hypertension produced additional MAP variability that was independent of SAD (Intact-Sham=4.6+/-0.4, Intact-Wrap=6.2+/-0.6, SAD-Sham=6.3+/-0.5, SAD-Wrap=10.8+/-1.5). In a separate group of rats, the sympathoadrenal contribution to MAP was assessed by the depressor response to ganglionic blockade and plasma norepinephrine at rest and after neuronal uptake inhibition with desipramine. The depressor response to ganglionic blockade was significantly increased by renal wrap and by SAD (Intact-Sham=-49+/-2 mm Hg, Intact-Wrap=-73+/-4 mm Hg, SAD-Sham=-77+/-5 mm Hg, SAD-Wrap=-96+/-6 mm Hg). In the 3 groups with enhanced ganglionic blockade responses, desipramine caused a significant increase in plasma norepinephrine. These results indicate that SAD does not alter the development of renal wrap hypertension but does increase the sympathoadrenal contribution to MAP in both normotensive and hypertensive animals.

Paroxysmal hypertension due to sinoaortic baroreceptor denervation in humans.

A 41-year-old man with a remote history of neck and mediastinal radiation was seen with severe paroxysms of hypertension, headache, and cutaneous flushing after bilateral carotid bypass surgery. Investigation revealed marked parallel fluctuations in blood pressure and heart rate and elevation of plasma norepinephrine to 1164 pg/ml during a paroxysm. We systematically evaluated his arterial and cardiopulmonary baroreceptor reflex function by assessing changes in heart rate, arterial pressure, and efferent muscle sympathetic nerve activity, which was measured directly by the microneurographic technique. Elevating resting arterial pressure from 130/88 to 164/100 mm Hg with phenylephrine or lowering it to 88/56 mm Hg with nitroprusside produced no reflex changes in heart rate or efferent sympathetic nerve activity. In contrast, decreases in cardiac filling pressures with lower body negative pressure produced a marked increase in sympathetic nerve activity. These findings indicate complete loss of the afferent limb of the arterial baroreceptor reflex but preservation of the cardiopulmonary baroreceptor reflex. They suggest that both carotid and aortic baroreceptors were impaired by the previous radiation and surgery. Despite the loss of arterial baroreceptor function, the patient did not have sustained hypertension. The paroxysms of hypertension appear to be due to spontaneous fluctuations in central sympathetic drive not buffered by arterial baroreceptors in a manner similar to that seen in sinoaortic-denervated animals.

Cardiac volume receptor reflex in borderline hypertensive rats.

With increased dietary NaCl intake (8% NaCl), borderline hypertensive rats (BHR) develop hypertension and exhibit an exaggerated natriuresis in response to intravenous isotonic saline volume expansion. The exaggerated natriuresis is mediated by the concurrent exaggerated withdrawal of efferent renal sympathetic nerve activity since prior renal denervation eliminates the exaggerated natriuretic response. It was the objective of the present study to examine cardiac volume receptor reflex control of efferent renal sympathetic nerve activity in BHR made hypertensive by increased dietary NaCl intake. BHR were fed either 1% or 8% NaCl from age 4 to 16 weeks. BHR fed 8% NaCl were hypertensive (148 +/- 9 mmHg) compared with BHR fed 1% NaCl (115 +/- 6 mm Hg, p < 0.05). In one protocol, measurements of right atrial pressure and efferent renal sympathetic nerve activity were made in sinoaortic-denervated BHR before and during a 10% body weight intravenous isotonic saline volume load. Compared with 1% NaCl BHR, 8% NaCl BHR showed both a greater maximal inhibition of efferent renal sympathetic nerve activity (-67 +/- 4% versus -31 +/- 3% of control, p < 0.05) and gain (-22.0 +/- 2.3 versus -9.7 +/- 1.7%/mm Hg, p < 0.05). In a second protocol, measurements of efferent renal sympathetic nerve activity were made in sinoaortic-denervated BHR before and during graded frequency stimulation of the central portion of the sectioned vagus nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Sympathoexcitatory response to cyclosporin A and baroreflex resetting.

We postulate that the sympathoexcitatory response associated with the immunosuppressive agent cyclosporin A is due to an upward resetting of the arterial baroreflex. We performed studies in conscious intact and sinoaortic-denervated rabbits instrumented with catheters and renal nerve electrodes. In intact rabbits, cyclosporin A (20 mg/kg i.v., 30 minutes) produced significant increases in renal sympathetic nerve activity (100% to 269 +/- 74%, P < .05) but did not increase mean arterial pressure. In intact rabbits, we determined arterial baroreflex curves relating renal sympathetic nerve activity and heart rate to mean arterial pressure by producing ramp increases (intravenous phenylephrine) and decreases (intravenous nitroprusside) in mean arterial pressure. Cyclosporin A treatment produced a shift of the midrange of the baroreflex control of heart rate (78.0 +/- 4.1 to 84.6 +/- 4.7 mm Hg, P < .05) and renal sympathetic nerve activity (74.6 +/- 3.9 to 87.0 +/- 4.8 mm Hg, P < .05). Vehicle administration produced no effects on arterial baroreflex curves relating renal sympathetic nerve activity and heart rate to mean arterial pressure. Compared with vehicle treatment, cyclosporin A reduced the maximum gain of heart rate (-5.6 +/- 0.6 versus -3.1 +/- 0.8 beats per minute per millimeter of mercury, P < .05) but had no effect on the maximum gain of renal sympathetic nerve activity. In conscious sinoaortic-denervated rabbits, cyclosporin A had no effect on mean arterial pressure (95.7 +/- 7.3 to 91.8 +/- 10.8 mm Hg), renal sympathetic nerve activity (100% to 110 +/- 6%). and heart rate (287 +/- 10 to 279 +/- 8 beats per minute). However, when the same sinoaortic-denervated rabbits were anesthetized with sodium pentobarbital, cyclosporin A (20 mg/kg i.v.) produced increases in renal sympathetic nerve activity (100% to 189 +/- 27%). These data indicate (1) that the sympathoexcitatory response to cyclosporin A depends on baroreceptor afferent input in the conscious state and (2) that this response involves an upward resetting of the arterial baroreflex.

Sympathoinhibitory responses to 2-methylserotonin during changes in sodium intake.

The vagal-mediated reflex responses elicited by the selective serotonin type 3 receptor agonist 2-methyl-serotonin were examined by administration (6.25, 12.5, 25, and 50 micrograms/kg i.v.) of 2-methylserotonin to sinoaortic-denervated rats with either intact or sectioned vagi. To study the influence of dietary sodium intake on 2-methylserotonin-induced vagal reflex responses, we performed experiments in rats fed either a high or low sodium diet. Left ventricular end-diastolic pressure was significantly higher in animals on high than low salt diet. However, mean arterial pressure and heart rate were similar in high and low salt groups. In rats with intact vagi, 2-methylserotonin produced a dose-dependent increase in afferent vagal nerve activity and a dose-dependent decrease in efferent renal sympathetic nerve activity, mean arterial pressure, and heart rate. The sympathoinhibitory responses of decreased efferent renal sympathetic nerve activity, mean arterial pressure, and heart rate were abolished by vagotomy and were not affected by changes in dietary sodium intake. We conclude that the sympathoinhibitory effect of 2-methylserotonin is due to stimulation of vagal afferents with inhibitory action on peripheral sympathetic nerve activity and that the sympathoinhibitory responses are unaffected by changes in dietary sodium intake.

Reflex control of blood pressure and heart rate by arterial baroreceptors and by cardiopulmonary receptors in the unanaesthetized cat.

Studies in unanaesthetized animals have reported that section of the carotid sinus and aortic nerves is accompanied by an increased blood pressure variability but not by a sustained blood pressure rise, thus questioning the role of arterial baroreceptors in the long term control of mean blood pressure values. However, sino-aortic denervation (SAD) does not produce denervation of all baroreceptor areas, and it has been suggested that aortic baroreceptor fibres in the vagus and cardiopulmonary vagal afferents that restrain sympathetic vasoconstrictor tone prevent blood pressure from permanently rising. In unanaesthetized cats we recorded blood pressure intra-arterially for 8-12 h when baroreflexes were intact, 7 days after SAD and 1-2 days additional bilateral cervical vagotomy. Blood pressure signals were analysed by computer to provide means and coefficients of variation (CV, variabilities) for each recording period. In intact cats, mean blood pressure was 99 +/- 7 mmHg (average +/- s.e.) and CV 6 +/- 1%. SAD did not alter mean blood pressure but markedly increased CV (12 +/- 2%; P less than 0.01). Additional vagotomy did not alter mean blood pressure (104 +/- 6 mmHg), nor did it alter the increased CV observed after SAD alone. Vagotomy failed to affect mean blood pressure and CV even when performed in cats with intact carotid and aortic nerves. The lack of effect of vagotomy did not depend on simultaneous section of afferent and efferent fibres, because selective blockade of the latter by atropine also failed to affect mean blood pressure and CV.(ABSTRACT TRUNCATED AT 250 WORDS)

Inflammation is involved in the organ damage induced by sinoaortic denervation in rats.

OBJECTIVE: The present study was designed to test the hypothesis that inflammation is involved in the end-organ damage (EOD) induced by sinoaortic denervation (SAD) in rats. METHOD: SAD was performed in male Sprague-Dawley rats at the age of 10 weeks. Under anaesthesia, aortic nerves were cut and the sinus region of the carotid artery was stripped and painted with 10% phenol. Pathological evaluation of EOD and the determination of plasma or tissue levels of the factors related to inflammation, including thromboxane B2 (TXB2) interleukin-1 (IL-1), tumour necrosis factor alpha (TNF-alpha) and reactive oxygen species (ROS) were performed at 16 weeks after SAD. Pathological evaluation of EOD included heart weight ratio, myocardial and blood vessel hydroxyproline and collagen volume fraction, glomerular injury score and number of infiltrating inflammatory cells. Indomethacin (20 mg/kg per day, orally) or vitamin E (100 mg/kg per day, orally) was administered for 12 weeks, beginning from 4 weeks after SAD, to observe their effects on SAD-induced EOD. RESULTS: There were significant fibrosis and inflammatory infiltration in the myocardium and blood vessels, represented by higher hydroxyproline and collagen volume fraction, and a large amount of inflammatory cells in the tissues of SAD rats. Heart weight and kidney glomerular injury score were significantly higher in SAD than in sham-operated rats. Plasma TXB2, TNF-alpha, IL-1 and tissue ROS increased significantly after SAD. Indomethacin and vitamin E significantly decreased the contents of some factors related to inflammation in SAD rats. Both drugs also alleviated myocardial and vessel fibrosis, inflammatory infiltration and kidney damage. CONCLUSION: Inflammation is involved in the organ damage induced by SAD in rats.

Relationships between kallikrein secretion, kallikrein excretion and beta-adrenoceptors in kidney cortical slices from neurogenic hypertensive dogs.

1. Sinoaortic denervation (SAD) in dogs is characterized by an increase in blood pressure and heart rate as well as the development of renal morphological lesions similar to those observed in essential hypertension in human subjects. To assess the effect of SAD on the secretion of kallikrein kinin systems (KKS), we studied the in vitro secretion of kallikrein by renal cortical slices of normal and neurogenic hypertensive dogs (1 and 18 months after SAD). The method using renal cortical slices allowed the study of secretion of kallikrein independently of renal perfusion pressure. The number of renal beta-adrenoceptors was measured by [125I]-cyanopindolol binding. 2. SAD was associated with a marked increase in urinary kallikrein excretion at one month and a significant decrease at 18 months when compared with controls. Both changes were statistically significant (P < 0.05). Concurrently, a progressive increase in in vitro kallikrein secretion was observed (+80 +/- 10% and +179 +/- 48%, 1 and 18 months after SAD, respectively). Moreover, the cortical slices obtained from sinoaortic denervated dogs contained more kallikrein than the control cortical slices (+32 +/- 16% and +55 +/- 7%, 1 and 18 months after SAD, respectively). 3. Renal beta-adrenoceptor number significantly (P < 0.05) decreased 18 months after SAD from 18 +/- 2 to 8 +/- 3 fmol mg-1 protein without any change in affinity constant. 4. Although there was no test of association, because the number of renal beta-adrenoceptors decreased whereas kallikrein secretion increased, the present data could suggest a beta-adrenoceptor-mediated inhibition of kallikrein secretion. These results show that although the urinary kallikrein is decreased, the tissue secretory capacities are enhanced. This could suggest a renal compensatory mechanism possibly involved in tissue protection in dogs after SAD, although such a mechanism is not sufficient to reverse hypertension.

Fos immunoreactivity in the diagonal band and the perinuclear zone of the supraoptic nucleus after hypertension and hypervolaemia in unanaesthetized rats.

We used Fos immunocytochemistry to study the effects of hypertension and hypervolaemia on neurones in the diagonal band of Broca and the perinuclear zone of the supraoptic nucleus, two nuclei that are both involved in the baroreceptor regulation of vasopressin neurones in the supraoptic nucleus. In addition, we used sino-aortic denervation to examine the role of arterial baroreceptors in the response to these haemodynamic changes. Sham-operated and sino-aortic denervated rats were infused with phenylephrine sufficient to increase blood pressure for 2 h. Control rats were infused with the same volume of isontonic saline. Only Sham sino-aortic denervated rats showed reflex bradycardia in response to the increased blood pressure. Volume expansion was produced by infusing the rats with isotonic saline equal to 10% of their body weight for 10 min, which significantly increased central venous pressure. In the diagonal band of Broca and the perinuclear zone, the number of Fos-positive neurones was significantly increased after phenylephrine infusion. Sino-aortic denervation blocked the significant increase in both regions. After volume expansion, a significant increase in Fos staining was observed only in the perinuclear zone of the supraoptic nucleus. This increase was not blocked by sino-aortic denervation. Our results indicate that both the diagonal band of Broca and the perinuclear zone of the supraoptic nucleus are activated by stimulating arterial baroreceptors; however, the perinuclear zone of the supraoptic nucleus is stimulated during volume expansion. Furthermore, the activation of perinuclear zone of the supraoptic nucleus after volume expansion is not dependent on intact arterial baroreceptors.

Association of blood pressure variability with induction of atherosclerosis in cholesterol-fed rats.

The influence of increased lability of blood pressure on the development of aortic atherosclerosis was examined. Because sinoaortic denervation (SAD) produced increased lability of blood pressure without blood pressure elevation, the development of atheromatous plaque was examined in SAD rats. These rats were fed a high-cholesterol diet and were denuded of endothelium so that development of atherosclerosis was accelerated. Five groups of male Wistar rats were used: A) controls, B) high-cholesterol diet (HC), C) HC+denudation (DN), D) HC+DN+renal artery clipping (2K1C), and E) HC+DN+sinoaortic denervation (SAD). Denudation was accomplished by scraping the aortic lumen with a balloon catheter, and hypertension was induced by clipping the left renal artery. After recording blood pressure and heart rate for 6 weeks, the rats were killed, blood samples were collected, and thoracic aortas were removed for pathologic examination. All the groups of rats fed a high-cholesterol diet developed marked hypercholesterolemia and hypotriglyceridemia. High-cholesterol diet alone could not induce aortic atherosclerosis, whereas aorta of HC+DN rats showed slight intimal thickening with smooth muscle cell proliferation. On the other hand, aorta of HC+DN + 2K1C rats showed marked atheromatous plaque with prominent cellular proliferation, and aorta of SAD rats also showed mild to moderate atheromatous plaque. Accordingly, we concluded that increased variability in circadian blood pressure per se, as well as hypertension, could induce aortic atherosclerosis in the hypercholesterolemic and endothelium-denuded rats.

Increased extracellular concentration of norepinephrine in the hypothalamus by sinoaortic denervation.

To determine whether baroreflex can affect the norepinephrine system in the hypothalamus, the extracellular concentration of norepinephrine were measured by the brain dialysis technique in sinoaortic denervated rats (SAD). Twenty-four hours after sinoaortic denervation, systolic blood pressure and heart rate were significantly elevated, and norepinephrine concentration in perfusate of the posterior hypothalamus was significantly higher in SAD rats than in sham-operated rats. These results suggest that baroreflex could modify the activity of noradrenergic neuron projecting to the posterior hypothalamus.

Acute responses of renal nerve activity to microgravity induced by free drop in anesthetized rats.

To examine acute cardiovascular and autonomic responses to microgravity (microG), arterial pressure (AP), aortic flow velocity (AFV), central venous pressure (CVP), and renal nerve activity (RNA) were measured in anesthetized rats during 4.5 s of microG produced by free drop. A smooth and immediate reduction in gravity occurred during free drop, microG being achieved 100 ms after the start of the drop. Acute microG elicited an immediate and striking, but transient, decrease in RNA with no significant change in AP and AFV, but a significant decrease in CVP. The decrease in RNA lasted 2 s, then RNA recovered to the control level despite the G value remaining at < 0.001 for 4.5 s. The RNA decrease was attenuated or completely abolished by sinoaortic denervation, vagotomy, or sinoaortic denervation plus vagotomy. These results suggest that acute microG conditions stimulate sinoaortic and cardiopulmonary mechanoreceptors and suppress RNA.

Static muscle contraction elicits a baroreflex-dependent increase in glutamate concentration in the ventrolateral medulla.

In anesthetized cats, static contraction of the hindlimb reflexly increases mean arterial pressure (MAP). This cardiovascular adjustment is reduced by the arterial baroreflex. Both of these reflex responses are mediated through activation of ventrolateral medullary (VLM) regions. We tested the hypothesis that the concentration of glutamate (Glu) increases in the caudal ventrolateral medulla (cVLM) during static hindlimb contractions in anesthetized cats, and that barodenervation reduces this elevation in Glu levels. Static contractions of the triceps surae muscle of one hindlimb were evoked by electrical stimulation of the peripheral ends of cut L7 and S1 ventral roots. After the insertion of the microdialysis probes and a 3-h recovery period, a 2-min static contraction increased MAP by 47 +/- 7 mmHg. The concentration of Glu increased from 606 +/- 189 to 1042 +/- 228 nM. These results were repeatable in that Glu, as well as MAP, rose by a similar amount in two subsequent contractions. By contrast, in a subset of cats paralyzed prior to the third contraction, neither MAP nor Glu were significantly increased over baseline levels during the third stimulation period. In a third group of cats, hindlimb contraction increased MAP and Glu levels. However, the Glu release was attenuated in subsequent contractions after these cats were barodenervated. During the same periods of stimulation, the denervation accentuated the rise in MAP. These data demonstrate that static contraction of the hindlimb increases the extracellular concentration of Glu in the cVLM. Further, our study implicates this neurotransmitter in the baroreflex mediated reduction of the pressor reflex response to static muscle contraction.