Kenju Miki

Acute shifts of baroreflex control of renal sympathetic nerve activity induced by treadmill exercise in rats

The present study aimed to investigate whether there was a resetting of the baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate (HR) during exercise. Wistar female rats (n= 11) were chronically implanted with catheters for the measurement of systemic arterial (Pa) and central venous pressures and with electrodes for measurement of RSNA and electrocardiogram (ECG) at least 3 days before study. The baroreflex curve for RSNA was determined by changing Pa using rapid intravenous infusions of phenylephrine and nitroprusside. The baroreflex response curves for RSNA and HR were characterized by an inverse sigmoid function curve from which the response range, gain, centring point and minimum response were estimated. Exercise shifted the Pa‐RSNA baroreflex curve upward and to the right and was associated with increases in response range of 122 ± 44 % (P < 0.05), maximum response of 173 ± 40 % (P < 0.05), maximum gain of 149 ± 66 % (P < 0.05) and midpoint pressure of 15 ± 5 mmHg (P < 0.05) compared with the pre‐exercise level. After cessation of exercise, the Pa‐RSNA baroreflex curve was suppressed vertically with a significant decrease in maximum response of 57 ± 14 % (P < 0.05) compared with the pre‐exercise level. These data suggest that the right‐upward shift of baroreflex control of sympathetic nerve activity may play a critical role in raising and stabilizing Pa during exercise. The suppression of the baroreflex control of sympathetic nerve activity may partly explain the post‐exercise inhibition of sympathetic nerve activity and contribute to the post‐exercise hypotension.

Chronic Angiotensin II Infusion Causes Differential Responses in Regional Sympathetic Nerve Activity in Rats

Angiotensin II (AngII)–induced hypertension in experimental animals has been proposed to be attributed in part to activation of the sympathetic nervous system. This sympathetic activation appears to be accentuated in animals consuming a high-salt diet (AngII-salt hypertension). However, accurate quantification of sympathetic activity is difficult, and controversy remains. It is particularly important to ask which are the critical vascular beds targeted by increased sympathetic nerve activity (SNA) in AngII-salt hypertension. To address this issue, mean arterial pressure and renal SNA or lumbar SNA were continuously recorded during a 5-day control period, 11 days of AngII (150 ng/kg per minute, SC), and a 5-day recovery period in conscious rats on a high-salt (2% NaCl) diet. Although mean arterial pressure reached a new steady-state level of 30 to 35 mm Hg above control levels by the end of the AngII period, renal SNA decreased by 40% during the first 7 days of AngII and then returned toward control levels by day 10 of AngII. In contrast, lumbar SNA remained at control levels throughout the AngII period. In another experiment we measured hindlimb norepinephrine spillover in conscious rats on normal (0.4%) or high- (2.0%) salt diets before and during 14 days of AngII administration. AngII had no significant affect on hindlimb norepinephrine spillover in either group. We conclude that chronic AngII modulates renal and lumbar SNAs differentially in rats consuming a high-salt diet and that AngII-salt hypertension in the rat is not caused by increased SNA to the renal or hindlimb vascular beds.

Method for Continuous Measurements of Renal Sympathetic Nerve Activity and Cardiovascular Function During Exercise in Rats

The sympathetic nervous system is believed to play a major role in regulating cardiovascular function during exercise. However, only a few direct measurements of sympathetic nervous activity during whole body dynamic exercise have been attempted. In the present study, we have established a method to allow routine measurement of renal sympathetic nerve activity (RSNA) and cardiovascular function during treadmill exercise in rats. We trained Wistar rats to run on the treadmill for a week before the surgery. At least 2 days before the experiment, electrodes for recording RSNA, electrocardiogram and electromyogram, and catheters for the measurements of systemic arterial and central venous pressures were implanted under aseptic conditions. Satisfactory signal to noise ratios were obtained in 80%, 60% and 40% of the group at 1‐3 days, 4‐7 days and 8‐10 days after the surgery, respectively. RSNA was successfully recorded without contamination by external noise during treadmill exercise. Treadmill exercise resulted in an abrupt increase in RSNA, by 82% at 0.5 min, and then reached a stable level of ∼40% during the period of 5‐30 min after the onset of treadmill exercise. This experimental model allows us to study the neural mechanisms involved in the regulation of cardiovascular function during dynamic exercise in rats.

Lumbar sympathetic nerve activity and hindquarter blood flow during REM sleep in rats

The present study aimed to investigate the response of lumbar sympathetic nerve activity (LSNA) to the onset of rapid eye movement (REM) sleep and its contribution to the regulation of muscle blood flow during REM sleep in rats. Electrodes for the measurements of LSNA, electroencephalogram, electromyogram and electrocardiogram and a Doppler flow cuff for the measurements of blood flow in the common iliac and mesenteric arteries, also catheters for the measurements of systemic arterial and central venous pressures were implanted chronically. REM sleep resulted in a step increase in LSNA, by 22 ± 9% (mean ±s.e.m., P < 0.05), a reduction of iliac vascular conductance, by −16 ± 3% (P < 0.05) and a gradual increase in systemic arterial pressure, reaching a maximum value of 8.1 ± 2.0 mmHg (P < 0.05) at 89 s after onset of REM sleep, while mesenteric vascular conductance increased simultaneously by 5 ± 2% (P < 0.05). There was a significant (Pearsons correlation coefficient = 0.94, P < 0.05) inverse linear relationship between LSNA and the iliac blood flow. Unilateral lumbar sympathectomy blunted the reduction of iliac blood flow induced by the onset of REM sleep. The present observations suggest that the onset of REM sleep appears to be associated with a vasodilation in viscera and a vasoconstriction in skeletal muscle, such that systemic arterial pressure increases during REM sleep in rats.

Acute shifts in baroreflex control of renal sympathetic nerve activity induced by REM sleep and grooming in rats.

The present study aimed to determine the impact of  REM sleep and grooming on the baroreflex stimulus–response curve for renal sympathetic nerve activity (RSNA). At least 3 days before study, Wistar female rats (n= 12) were chronically implanted with catheters to measure systemic arterial pressure (Pa) and to intravenously infuse vasoactive drugs. In addition, electrodes were placed for measurements of RSNA, electroencephalogram, trapezius electromyogram and electrocardiogram. The baroreflex curve for RSNA was determined by changing Pa using rapid intravenous infusions of phenylephrine and nitroprusside and then fitted to an inverse sigmoid function curve. REM sleep induced a vertical suppression of the Pa–RSNA baroreflex curve, which was characterized by significant decreases in the maximum response (by 72.0%, P < 0.05) and the maximum gain (by 4.02% mmHg−1, P < 0.05) compared with NREM sleep level. Grooming shifted the Pa–RSNA baroreflex curve upward and to the right, which was associated with increases in the maximum response (by 45.2%, P < 0.05), the minimum response (by 20.7%, P < 0.05) and the pressure at the centring point (by 11.1 mmHg, P < 0.05). These data suggest that the Pa–RSNA baroreflex curve was shifted acutely and differently in a state‐dependent manner during natural sleep and wake cycle in rats.

The contribution of brain angiotensin II to the baroreflex regulation of renal sympathetic nerve activity in conscious normotensive and hypertensive rats

Angiotensin II receptor density in the brain is elevated when dietary salt intake is raised or in the state of hypertension. The aim of this study was to evaluate whether the angiotensin II modulation of the baroreceptor control of renal sympathetic nerve activity was altered under these conditions. Wistar rats, fed either a regular (0.25% w/w sodium) or high‐salt diet (3.1% w/w sodium), or stroke‐prone spontaneously hypertensive rats (SHRSPs) were implanted with cannulae in the carotid artery, jugular vein and the cerebroventricle and with recording electrodes on the renal sympathetic nerves. Three days later, baroreceptor gain curves were generated for renal sympathetic nerve activity and heart rate before and following intracerebroventricular (i.c.v.) administration of losartan (15 μg) to block angiotensin AT1 receptors. The rats fed a regular diet had a mean blood pressure of 116 ± 3 mmHg and heart rate of 467 ± 25 beats min−1, which remained unchanged after the i.c.v. administration of losartan. The sensitivity or curvature coefficient of the baroreceptor curve for renal sympathetic nerve activity was increased by 36% (P < 0.05) following losartan. In the rats fed a high‐salt diet, all cardiovascular variables and the losartan‐induced increase in the baroreceptor curvature coefficient for renal sympathetic nerve activity (29%) were similar to values in rats on the regular sodium diet. The heart rate baroreceptor curvature coefficient was not altered in either the rats fed a regular or a high‐salt diet. The slope of the renal sympathetic nerve activity baroreflex gain curve in the SHRSPs was less and the increase following administration of losartan (54%) was greater than in the Wistar rats. These data indicate that in the conscious state, the tonic inhibitory action of brain angiotensin II on the baroreflex regulation of renal sympathetic nerve activity was unaffected by raised dietary sodium, but its role was enhanced in the SHRSPs.

Functional role of diverse changes in sympathetic nerve activity in regulating arterial pressure during REM sleep.

STUDY OBJECTIVES This study aimed to investigate whether REM sleep evoked diverse changes in sympathetic outflows and, if so, to elucidate why REM sleep evokes diverse changes in sympathetic outflows. MEASUREMENTS Male Wistar rats were chronically implanted with electrodes to measure renal (RSNA) and lumbar sympathetic nerve activity (LSNA), electroencephalogram, electromyogram, and electrocardiogram, and catheters to measure systemic arterial and central venous pressure; these parameters were measured simultaneously and continuously during the sleep-awake cycle in the same rat. RESULTS REM sleep resulted in a step reduction in RNSA by 36.1% ± 2.7% (P < 0.05), while LSNA increased in a step manner by 15.3% ± 2% (P < 0.05) relative to the NREM level. Systemic arterial pressure increased gradually (P < 0.05), while heart rate decreased in a step manner (P < 0.05) during REM sleep. In contrast to REM sleep, RSNA, LSNA, systemic arterial pressure, and heart rate increased in a unidirectional manner associated with increases in physical activity levels in the order from NREM sleep, quiet awake, moving, and grooming state. Thus, the relationship between RSNA vs. LSNA and systemic arterial pressure vs. heart rate observed during REM sleep was dissociated compared with that obtained during the other behavioral states. CONCLUSIONS It is suggested that the diverse changes in sympathetic outflows during REM sleep may be needed to increase systemic arterial pressure by balancing vascular resistance between muscles and vegetative organs without depending on the heart.

Sympathetic nerve activity during sleep, exercise, and mental stress

This brief review describes recent findings on the differential regulation of sympathetic nerve activity and its role in regulating systemic arterial pressure during rapid eye-movement sleep, non-rapid-eye movement sleep, exercise and freezing behavior (mental stress). We describe the mechanisms underlying the differential regulation of sympathetic outflows and how they act in concert to orchestrate adjustments of cardiovascular function for the whole body, which are optimized to match changes in organ activity in daily activity.

Differential effects of behaviour on sympathetic outflow during sleep and exercise

The responses of renal and lumbar sympathetic outflow to changes in behavioural states were reviewed in this paper. During rapid eye movement (REM) sleep, renal sympathetic nerve activity was decreased while lumbar sympathetic nerve activity increased. These diverse changes in sympathetic nerve activity observed during REM sleep help explain the responses in regional blood flow to REM sleep; that is renal blood flow increased while muscle blood flow decreased. By contrast, exercise increased both renal and muscle sympathetic nerve activity. The degree of physical activity was correlated with the magnitude of the increases in renal and muscle sympathetic nerve activity. There was a significant (P < 0.05) linear relationship between renal sympathetic nerve activity and systemic arterial pressure over the transition between non‐rapid eye movement (NREM) sleep, quiet awake, moving and grooming states in the rats. This suggests that sympathetic outflows seem to be modulated quantitatively to meet cardiovascular demand caused by changes in the level of physical activity. It is therefore concluded that sympathetic outflow seems to be regulated in a state‐specific manner during sleep and exercise.

Role of cardiac‐renal neural reflex in regulating sodium excretion during water immersion in conscious dogs

The present study was undertaken to determine the role of cardiopulmonary mechanoreceptors in inducing the sustained reduction of renal sympathetic nerve activity (RSNA) and concomitant changes in sodium excretion occurring during water immersion (WI) in intact dogs. Seven cardiac‐denervated dogs were chronically instrumented for measuring RSNA, systemic arterial (Pa), central venous (Pcv) and left atrial pressures (Pla). WI initially decreased RSNA in cardiac denervated dogs by 10.0 ± 5.5 %; thereafter the RSNA fell to a nadir of 18.5 ± 5.6 % (P < 0.05) at 40–80 min of WI and then returned toward the pre‐immersion level. Renal sodium excretion increased significantly by 211 ± 69 % (P < 0.05) only during the first 20–40 min of WI. WI increased Pa, Pcv and Pla in a step manner from 94 ± 3 to 108 ± 3 mmHg (P < 0.05), from 1.4 ± 0.5 to 12.3 ± 1.0 mmHg (P < 0.05) and from 4.9 ± 0.6 to 15.4 ± 1.2 mmHg (P < 0.05), respectively. These responses in RSNA and sodium excretion to WI in the cardiac‐denervated dogs were significantly (P < 0.05) attenuated compared with those in a previous group of intact dogs. These data suggest that the attenuated responses of neural and excretory response to WI observed in cardiac‐denervated dogs can be attributed to an interruption of afferent input originating from the cardiopulmonary mechanoreceptors to the central nervous system.