Heart rate variability,a target for the effects of angiotensin II in the brain of the trout Oncorhynchus mykiss

This study was conducted on unanesthetized rainbow trout equipped with two ECG electrodes and with an intracerebroventricular (i.c.v.) micro-guide. The ECG signal was recorded during three experimental sessions of 30 min and the heart rate variability (HRV) spectral analysis was performed during stabilized periods of recording. The first recording session was conducted during the control period and the mean heart rate (HR) of the trout was 44+/-2 bpm. The total power spectral density (PSD) of the R-R interval signal of the ECG was 21233+/-4400 ms(2)/Hz. A major high frequency (HF) spectral band centered at 0.16 Hz and a minor low frequency (LF) spectral band centered at 0.04 Hz were the two main components of the PSD. An i.c.v. injection of 0.5 microl of vehicle during the second session had no significant statistical effect, either on the mean HR (43+/-2 bpm), the total PSD (24693+/-6394 ms(2)/Hz) or on the center frequency and power of the two main spectral bands. Conversely, an i.c.v. injection of ANGII (1.5, 6.25 and 50 pmol) during the third recording session induced a significant increase in the mean HR (+3%, +15%, +30%, respectively) but the effect of the peptide was more obvious on the total PSD which was profoundly decreased (-27%, -65%, -76%, respectively). The two main spectral bands of the PSD were totally blunted after the injection of 50 pmol of ANGII. In another group of control trout, intraperitoneal (i.p.) injection of atropine abolished the PSD of the R-R interval signal of the ECG demonstrating that the parasympathetic system is the main contributor of HRV in trout. Our results have thus demonstrated for the first time, at least in a non-mammalian species, that i.c.v. injection of native ANGII profoundly reduces HRV. We hypothesize that ANGII in the brain of the trout alters the pattern of the electrical activity along preganglionic cardiac vagal motoneurons.     

偏头痛患者的自主神经功能及其定量测定

用心率变异频谱分析定量测定６５例偏头痛患者和５０例健康人仰卧位和站立位自主神经系统功能。结果发现，偏头痛患者站立位中频段积分较对照组显著降低（Ｐ〈０．００１），表明其交感神经功能低下，且随着疼痛程度的增加及病程的延长，其交感神经功能低下的程度迹越重，本文还初步探讨了其机理及临床应用意义。     

Thoracic sympathectomy: effects on hemodynamics and baroreflex control

Endoscopic thoracic sympathectomy at T2-T4 is an effective and safe treatment for primary axillary and palmar hyperhidrosis and facial blushing refractory to conventional treatment. T2 and T4 ganglia however are in the direct pathway of sympathetic innervation of the heart and part of the vasomotor nerves. In this study we investigate possible changes in steady-state hemodynamics as well as in beat-to-beat cardiovascular control after thoracoscopic sympathectomy of T2–T4. In 12 patients we measured continuously heart rate (HR) and blood pressure (BP) (non-invasively with Finapres™) during rest and during deep inspiration, in supine and sitting position as well as during a change from lying to standing. Stroke volume (SV) and total peripheral resistance (TPR) were estimated from the BP recordings by the Modelflow method. Markers for cardiovascular control were obtained from power and cross-spectra of BP and HR. After sympathectomy, only in the sitting position was mean HR decreased, while TPR and BP (diastolic and mean) were lower in the supine as well as sitting positions. SV clearly increased. Low frequency power in HR and BP was significantly decreased, just like the max/min ratio in HR after standing up, indicating a diminished capacity in sympathetic vasomotor control. High frequency power of HR as well as baroreflex sensitivity, both parasympathetic markers, did not change in a statistically significant manner. Conclusion: Besides altering steady-state hemodynamics, a thoracic sympathectomy causes relatively small, though measurable changes in cardiovascular control, in particular of peripheral vasomotion. Received: 3 January 2000, Accepted: 15 November 2001     

Closed-loop analysis of cardiovascular variability in rats under restraint stress

Causal transfer function analysis was applied to the heart rate variability and blood pressure variability in normotensive male Sprague-Dawley rats those were measured before, during, and after acute restraint stress. The causal transfer gain (CTG) from systolic blood pressure (SBP) to RR interval (RRI) and CTG from RRI to SBP were estimated. The mean value of the CTG from SBP to RRI in the low-frequency (LF) band (0.27-0.74 Hz) was significantly lower during the restraint period than during the baseline period and remained significantly lower during the recovery period. The mean value of the CTG from RRI to SBP in the LF band, in contrast, was significantly higher during the restraint period than during the baseline period, and during the recovery period it tended to return relatively rapidly to the baseline level. Arterial pressure tended to increase only at the onset of the restraint stress and then to decline not only during the restraint period but also during the recovery period, finally leveling off significantly below the baseline level. These results suggest that restraint stress suppresses the baroreflex control gain not only during the restraint period but also during the recovery period and that this results in the arterial hypotension during the recovery period.     

Facilitation of baroreflex-induced bradycardia by stimulation of specific hypothalamic sites in the rat

Hypothalamic stimulation generally inhibits baroreflex-induced bradycardia. However, we have noted discrete areas of the rat hypothalamus which facilitate reflex bradycardia. The effects of hypothalamic stimulation on baroreflex-induced changes in heart rate were investigated in urethane-anesthetized rats (1.2 g/kg, i.p.; n = 6) instrumented with femoral arterial and venous catheters. Bipolar electrodes (250 micron diameter) were implanted stereotaxically in the hypothalamus. Baroreflex-induced bradycardia was elicited by phenylephrine (PE) injection (8-20 micrograms/kg). Responses to stimulation (STIM) (50-150 microA, 80 Hz, 0.5 ms), PE, and Stim + PE were studied for 1 min. In the ventral medial and anterior hypothalamus, STIM caused transient increases in blood pressure and no changes in heart rate. Peak blood pressure was lower during STIM + PE than during PE (144 +/- 5 vs 164 +/- 3 mm Hg; P less than 0.05). However, STIM + PE resulted in a lower heart rate compared to PE (194 +/- 22 22 vs 270 +/- 17 bpm; P less than 0.05). At 1 min, the heart rate in STIM + PE rats remained lower than in PE rats (205 +/- 37 vs 319 +/- 16 bpm; P less than 0.05). Atropine administration indicated that the facilitation was primarily parasympathetic in nature. These results identify specific hypothalamic regions which facilitate baroreflex-induced bradycardia by parasympathetic mechanisms.     

Differentiation of autonomic nervous activity in different stages of coma displayed by power spectrum analysis of heart rate variability

The analysis of heart rate (HR) variability offers a noninvasive method to investigate autonomic nervous system activity in comatose patients. We analyzed three components of the HR variability in a group of comatose patients: the low-frequency band (LF), representing mainly sympathetic influence, the mid-frequency band (MF), representing sympathetic and parasympathetic influence, and the high-frequency band (HF), representing the parasympathetic influence. A value for sympathovagal balance was defined as LF/HF and MF/HF ratio. Moreover, the skin conductance level (SCL) and the skin conductance resistance (SCR) variability were recorded. The patient group consisted of 22 patients with traumatic brain injuries. Coma depth was assessed by the Glacow Coma Scale and artifact-free HR, SCL, and SCR were measured 75 times in the patient group. The results documented a significant gain in sympathetic nervous system activity corresponding with the state of emerging from coma. This gain was most pronounced in the HF component of the HR and in the sympathovagal balance between LF/HF. The findings in SCL and SCR variability endorsed this result. It is concluded that emerging from coma is accompanied by an increasing influence of the sympathetic nervous system on HR control. This leads to a change in the sympathovagal balance, i.e., a reintegration of parasympathetic and sympathetic activity. Received: 7 February 1996 / Accepted: 8 October 1997     

Cerebral asymmetry in the control of cardiovascular functioning: Evidence from lateral vibrotactile stimulation

Research has supported hemispheric specialisation in the regulation of cardiovascular functioning, with the left hemisphere being associated with parasympathetic functioning and the right hemisphere with sympathetic functioning. We sought to investigate this relationship further using vibrotactile stimulation applied to the palms. Our prediction was that vibrotactile stimulation applied to the left hand would result in increased heart rate and blood pressure, and that stimulation applied to the right hand would result in decreased heart rate and blood pressure. The results indicated significant differences in heart rate change scores in the predicted direction. No differences were noted for systolic or diastolic blood pressure. Hence the findings provide partial support for the lateralisation of autonomic functions.     

Role of neuropeptide Y (NPY) in cardiovascular responses to stress

Neuropeptide Y (NPY), a putative sympathetic neurotransmitter and neuromodulator, is released during sympathetic nerve stimulation and causes vasoconstriction and cardiodepression. Whether the release of NPY contributes to stress-induced cardiovascular responses was assessed by studying i/ plasma levels of circulating NPY-immunoreactivity (NPY-ir) during various stress paradigms and ii/ mechanisms of action of NPY in the cardiovascular system of the rat. Plasma NPY-ir was increased by all stress situations, such as transfer to a new environment (by 52%), exposure to cold water (4⁰C) (by 117%) and hemorrhage (4 ml/300 g body weight) (by 231%). The cold water, stressinduced, maximal increase in circulating plasma NPY-ir was delayed in relation to the peak pressor response by 10–20 min. Administration of NPY caused dose-dependent pressor responses that were greater in pithed rats - which have all centrally mediated circulatory reflexes removed - than in conscious rats. Infusion of a low pressor (8.5 ± 1.5 mm Hg) dose of norepinephrine into conscious rats potentiated NPY-mediated pressor responses 2-fold and also tended to increase bradycardic effect of a higher dose of NPY (by 19%). Thus hypertensive and bradycardic actions of NPY appear to depend on the level of adrenergic activity and on the interactions at the level of vascular smooth muscle, heart, and baroreceptor reflexes. During a hyperadrenergic state such as stress, cardiovascular effects of NPY may be greatly accentuated. NPY may enhance and prolong the stressinduced hypertensive responses while antagonizing adrenergic cardiostimulation.     

心率变异光谱分析定量测定偏头痛患者自主神经功能及其意义初探

心率变异光谱分析定量测定６５例偏头痛患者和５０例健康人仰卧位和站立位自主神经系统（ＡＮＳ）功能。结果发现，偏头痛患者站立位中频段积分较对照组显著降低（Ｐ＜０．００１），表明其交感功能低下，且随着疼痛程度的增加及病程的延长，其交感功能低下的程度亦越重。本文还初步探讨了其机理及临床应用意义。     

Morphine blocks the bradycardia associated with severe hemorrhage in the anesthetized rat

Progressive hemorrhage in the absence of tissue injury produces a biphasic response: an initial tachycardia, vasoconstriction and maintenance of arterial blood pressure by the baroreflex, followed by bradycardia, vasodilatation and hypotension due to the activation of a second ‘depressor’ reflex. The present study has investigated the effect of morphine (a μ-opioid receptor agonist) on the cardiac chronotropic response to a progressive hemorrhage at 2% total estimated blood volume (BV) min⁻¹ in the anesthetized rat. In control rats (20 μl saline intracerebroventricularly, i.c.v.) heart period initially decreased significantly (P < 0.05) by a maximum of 5.4 ± 0.8 ms from a baseline of 147.3 ± 2.2 ms after a blood loss of 8.3 ± 1.5% BV, and then increased significantly by a maximum of 43.0 ± 5.5 ms above the baseline after the loss of 34.5 ± 1.6% BV. Blood pressure was initially maintained and then fell during the hemorrhage. The increase in heart period was prevented by treatment with morphine (10 μg i.c.v.), and the fall in blood pressure delayed significantly. These effects of morphine were prevented by pretreatment with naloxone (20 μg i.c.v.). Intravenous (i.v.) administration of morphine (10 μg) had no effect on the response to hemorrhage. However, a clinically relevant dose of 0.5 mg · kg⁻¹ morphine (i.v.) abolished the bradycardia and delayed the fall in blood pressure associated with hemorrhage. These results indicate that morphine, acting on central nervous opioid receptors, can abolish the bradycardia and delay the hypotension associated with progressive hemorrhage, a pattern of response reminiscent of the effects of musculo-skeletal injury on the response to blood loss.     

Cardiovascular and dipsogenic effects of angiotensin II administered i.c.v. in Long-Evans and Brattleboro rats

The concurrent cardiovascular and dipsogenic effects produced by i.c.v. administration of angiotensin II (AII) have been investigated in vasopressin-deficient (Brattleboro) and control (Long-Evans) rats. When animals were allowed to drink during testing, the pressor effect of i.c.v. AII (500 ng) in Long-Evans rats (26 +/- 3/26 +/- 3 mm Hg) was significantly greater than that produced when drinking water was not available (19 +/- 2/18 +/- 2 mm Hg). There was a significant decrease in heart rate only when water was available. There was no pressor response to i.c.v. AII in Brattleboro rats not allowed to drink, whereas blood pressure increased by 17 +/- 3/14 +/- 1 mm Hg in response to i.c.v. AII when drinking water was present. There were no significant changes in heart rate following i.c.v. AII in Brattleboro rats. When baseline drinking was taken into account, Brattleboro rats still drank significantly more water than Long-Evans rats in response to i.c.v. AII. Pretreatment of Long-Evans rats with the V1 vasopressin antagonist, D(CH2)5Tyr(Et)DAVP, decreased the pressor effect of i.c.v. AII to a level not significantly different from that of Brattleboro rats allowed to drink. Under these conditions the amount drunk by Long-Evans rats was not significantly less than that drunk by Brattleboro rats. These results confirm that the central pressor actions of AII are mediated, in part, by release of vasopressin and suggest that the greater dipsogenic effect of i.c.v. AII in Brattleboro compared with Long-Evans rats may be due, partly, to its lesser pressor activity in these animals.     

Estrogen alters the bradycardia response to hypocretin-1 in the nucleus tractus solitarius of the ovariectomized female

Experiments were performed to investigate the effect of 17beta-estradiol (E; 30 pg/ml plasma) treatment (15-25 days) in the ovariectomized (OVX) female Wistar rat on the cardiovascular responses to hypocretin-1 (hcrt-1) in the nucleus tractus solitarius (NTS). In an initial series of experiments, the distribution of hcrt-1-like immunoreactivity within the region of the NTS was mapped in both OVX only and OVX+E animals. Hcrt-1 immunoreactivity was found throughout the NTS region in both groups of females, predominantly within the caudal interstitial, commissural, medial and lateral subnuclei of the NTS. The relative density of hcrt-1 immunoreactivity in all NTS subnuclei was similar in both female groups. Microinjections of hcrt-1 (0.5-10 pmol) into the caudal lateral and medial subnuclei of the NTS complex of the alpha-chloralose of the urethane-anaesthetized E-treated OVX rat elicited a dose-related decrease in heart rate (HR). On the other hand, although a dose-response effect on arterial pressure was evident, significant arterial pressure responses were observed only at the higher dose of hcrt-1 (>2.5 pmol). In the OVX only female rat, microinjection of hcrt-1 into similar NTS sites elicited a bradycardia and depressor response only at the highest dose of hcrt-1, and these responses were significantly smaller in magnitude than those elicited in the OVX+E animal. In addition, in the OVX only animals, a few sites within the caudal commissural subnucleus of the NTS complex were found at which hcrt-1 elicited tachycardia and pressor responses. Finally, it was found that the reflex bradycardia to the activation of arterial baroreceptors as a result of increasing systemic arterial pressure with phenylephrine (2-4 microg/kg) was significantly potentiated in the OVX+E animals only. These data suggest that hcrt-1 in the NTS of the female activates a neuronal circuit that controls the circulation and that the circulating level of E alters the sensitivity of these cardiovascular circuits to hcrt-1.     

Linear and non-linear 24 h heart rate variability in chronic heart failure

It has recently been demonstrated that SDNN of heart rate variability (HRV) is a useful independent prognostic tool in chronic heart failure (CHF). The purpose of the present study was to evaluate if spectral and non-linear analysis of 24-h HRV, considered markers of autonomic cardiac modulation, contain independent prognostic information in CHF patients. Twenty normal subjects and thirty consecutive outpatients with clinically stable CHF were studied for 2 years. Periods of 300 R-R intervals were analyzed from Holter recordings. The power spectral analysis, the slope of the linear relationship between log-power versus log-frequency (1/f), and the complexity content (using corrected conditional entropy; CCE) of the R-R series were calculated. The normalized power of the low frequency spectral component (LF) and the 1/f slope were significantly lower in patients compared to controls (respectively 30.1 +/- 3.0 vs. 48.6 +/- 3.4 and -1.27 +/- 0.04 vs. -1.08 +/- 0.05; P < 0.05). Moreover, the patients who died during the study presented a reduced LF (20.9 +/- 4.1 vs. 35.5 +/- 3.5 nu; P < 0.05) and a steeper 1/f slope (-1.40 +/- 0.09 vs. -1.21 +/- 0.04 nuts, P < 0.05) compared to survivors. These results remained significant in a logistic model including heart rate and SDNN. The information content present in spectral and non-linear analysis of HRV in CHF patients has prognostic relevance independently from the time domain measures of HRV. In particular, the reduction of LF power seems the best indicator among those considered.     

Nocturnal hypertension in mice consuming a high fructose diet

OBJECTIVE: To investigate the effect of fructose consumption on the light/dark pattern of blood pressure, heart rate and autonomic neural function in mice. BACKGROUND: Insulin resistant diabetes is associated with hypertension and autonomic dysfunction. There is evidence that the increasing incidence of diabetes may be related to dietary changes, including consumption of high levels of fructose. DESIGN/METHODS: C57/BL mice, instrumented with radiotelemetric arterial catheters, were fed a control or high fructose diet (60%). Cardiovascular parameters measured were light/dark pattern of mean arterial pressure (MAP), heart rate (HR) and variability (time and frequency domain). We also measured plasma insulin, glucose, lipids and angiotensin II (Ang II) as well as glucose tolerance. In situ hybridization was used to measure brainstem expression of tyrosine hydroxylase (TH) and Ang AT1a mRNA. RESULTS: Fructose diet (8 weeks) produced an increase in MAP, variance and low frequency domain (14+/-3 vs. 33+/-4 mm Hg(2), variance and 10+/-2 vs. 26+/-4 mm Hg(2), LF, control vs. fructose, P<0.01). The changes occurred only at night, a period of activity for mice. Glucose tolerance was attenuated in the fructose group. Fructose also increased plasma cholesterol (80+/-1 vs. 126+/-2 mg/dl, control vs. fructose, P<0.05) and plasma Ang II (18+/-5 vs.65+/-12 pg/ml, control vs. fructose, P<0.05). Depressor responses to alpha(1)-adrenergic blockade with prasozin were augmented in fructose-fed mice. Using quantitative in situ hybridization, we found that Ang AT1a receptor and TH mRNA expression were significantly increased in the brainstem locus coeruleus. CONCLUSION: A high fructose diet in mice produced nocturnal hypertension and autonomic imbalance which may be related to activation of sympathetic and angiotensin systems.     

Evaluation of autonomic nervous system function with spectral analysis of heart rate variability in a case of tetanus

The autonomic nervous system is affected in a wide variety of neurological disorders. Its dysfunction may play an important role in the clinical course and may result in serious complications, such as cardiac arrest. We report a case of tetanus who presented with severe autonomic nervous system dysfunction which was detected by spectral analysis of heart rate variability monitored over 24 h. This is a semi-quantitative method for evaluation of the status of the autonomic nervous system. In the present case, the analysis revealed profoundly decreased activity of both sympathetic and parasympathetic nervous system modulation of cardiac rhythm. The parasympathetic nervous system activity was more severely impaired than that of the sympathetic nervous system. The relative predominance of the sympathetic nervous system in the present case may have resulted in unopposed sympathetic nervous system hyperactivity manifested in this patient by tachycardia and excessive sweating. We further infer that the documented diminished buffering capacity of the autonomic nervous system may have lead to a sudden cardiac arrest in our case. Thus, spectral analysis of heart rate variability is a non-invasive and sensitive method for evaluating the status of the autonomic nervous system of critically ill patients in the hospital setting.     

The impact of sleep disordered breathing on cardiovascular health in overweight children

BackgroundUp to 50% of overweight/obese children have obstructive sleep apnea (OSA) compared to up to 6% of normal weight children. We compared cardiovascular variables between normal weight and overweight/obese children with and without OSA, and controls.MethodsSeventy-four referred children and 24 normal weight non-snoring controls (8–18 years) were recruited. Referred children were grouped according to their obstructive apnea hypopnea index (OAHI): OSA (>1 event/h) or primary snoring (PS ≤ 1 event/h) and whether they were normal weight (BMI z-score <1.04) or overweight/obese (BMI z-score ≥ 1.04). Wake blood pressure (BP), heart rate (HR), and pulse transit time (PTT, an inverse continuous surrogate measure of blood pressure) during sleep were recorded.ResultsWake BP was higher in the overweight/obese OSA group than in the control, normal weight PS, and overweight/obese PS groups (p < 0.05 for all). During sleep, BP, and HR were elevated in the overweight/obese OSA group compared to those in non-snoring controls (p < 0.05). More children who were overweight/obese had reduced BP and HR dipping from wake to sleep than normal weight children. The BMI z-score predicted HR and PTT when asleep and both age and BMI z-score predicted BP when awake.ConclusionThis study showed that BMI has both combined and independent effects on BP and HR in children with OSA. We have previously shown that treatment of OSA reduces BP and suggest that treatment of OSA in the growing number of overweight/obese children may improve cardiovascular outcomes.     

Effects of an acute stressor on blood pressure and heart rate in rats pretreated with intracerebroventricular oxytocin injections

Oxytocin induces a long-lasting reduction of blood pressure in rats. The aim of the present study was to investigate the effects of an acute stressor on blood pressure and heart rate in rats previously exposed to repeated administration of intracerebroventricular (ICV) oxytocin. For this purpose oxytocin (0.3 microg, ICV) was administered to male rats once a day during 5 days. Blood pressure and heart rate were measured before and after treatment. In addition, blood pressure and heart rate were measured during 30 min after exposure to 10s of noise from an alarm clock. The oxytocin treatment reduced blood pressure significantly (systolic: 108+/-4.6 vs. 121+/-1.8, p<0.01, diastolic: 96+/-5.1 vs. 108+/-3.0, p<0.01), whereas heart rate remained unchanged. In contrast, systolic and diastolic blood pressure increased significantly after the exposure to the ringing alarm clock in the oxytocin-treated rats (p<0.05), and became equal to the blood pressure in controls. In addition, heart rate increased and stayed significantly higher in the oxytocin-treated rats compared to the controls during the 30 min observation period (ANOVA p<0.01). Twenty-four hours later, blood pressure was again significantly lower in the oxytocin-treated rats compared to controls (p<0.01). In conclusion, oxytocin decreased blood pressure without changing pulse rate. However, when the oxytocin-treated rats were subjected to the unexpected noise from a ringing alarm clock blood pressure and heart rate increased significantly. No such effect was observed in the control group. Thus repeated oxytocin treatment can, in spite of decreasing blood pressure during basal conditions, increase cardiovascular reactivity to some types of stressors.     

Evidence for a differential modulation of the alpha-2 adrenoceptors by angiotensin II in the nucleus tractus solitarii of the spontaneously hypertensive and the Wistar-Kyoto normotensive rats

An interaction between angiotensin II (Ang II) receptors and α₂-adrenoceptors was evaluated in the nucleus tractus solitarii (NTS) of the normotensive Wistar-Kyoto rat (WKY) and of the spontaneously hypertensive rat (SHR) using quantitative receptor autoradiography and cardiovascular analysis. In the WKY rat, Ang II promoted a dose-dependent increase in the IC₅₀ value ofl-noradrenaline when competing for [³H]p-aminoclonidine ([³H]PAC) binding sites, which reached a maximum of 400% with 10 nM of Ang II and was associated with a small decrease in theB₀ value (20%). In the SHR Ang II (0.1 nM) had an opposite effect leading to a decrease in the IC₅₀ value of about 57%, and no change was observed in theB₀ value. Saturation analysis also showed that Ang II (0.1 nM) increased theK_D value of [³H]PAC in the WKY strain but in contrast decreased theK_D value of [³H]PAC in the SHR. TheB_max value was not significantly changed neither in the WKY rat nor in the SHR. The cardiovascular analysis showed that a threshold dose of Ang II (0.05 pmol) counteracted the vasodepressor effect produced byl-noradrenaline coinjected in the NTS of the WKY rat. No effect was observed in heart rate. In the SHR no counteraction of thel-noradrenaline-induced vasodepressor effect was found, and in contrast a slight increase of the vasodepressor effect associated with a significant increase in the bradycardiac response was observed. The results give evidence for an antagonistic Ang II/α₂ receptor interaction in the cardiovascular part of the NTS of the WKY rat as previously observed in the Sprague-Dawley rat. However, this interaction is altered in the SHR, so that in this strain the Ang II/α₂ receptor interaction enhances α₂ affinity and possibly α₂ receptor function. This opposite effect observed in the SHR may represent one compensatory mechanism to counteract the development of high blood pressure in the SHR.     

Prenatal high salt programs enhanced sympathoadrenal activation of the cardiovascular response to restraint

We recently reported that feeding Sprague Dawley rats a high-salt diet during pregnancy programmed an exaggerated pressor and tachycardic response to restraint in adult female offspring. In the present investigation, a pharmacologic approach was used to determine the contribution of the sympathoadrenal system to the exaggerated response. Injection of a cocktail containing a ganglionic blocker (chlorisondamine) and a β-adrenoceptor antagonist (propranolol) prevented the stress-induced tachycardia and increase in blood pressure and abolished the difference between high-salt and normal-salt offspring. These data suggest that the prenatal high salt programmed a sympathoadrenal hyperresponsiveness to restraint stress.     

Neonatal nociception elevated baseline blood pressure and attenuated cardiovascular responsiveness to noxious stress in adult rats

Neonatal nociception has significant long-term effects on sensory perception in adult animals. Although neonatal adverse experience affect future responsiveness to stressors is documented, little is known about the involvement of early nociceptive experiences in the susceptibility to subsequent nociceptive stress exposure during adulthood. The aim of this study is to explore the developmental change in cardiovascular regulating activity in adult rats that had been subjected to neonatal nociceptive insults. To address this question, we treated neonatal rats with an intraplantar injection of saline (control) or carrageenan at postnatal day 1. The carrageenan-treated rats exhibited generalized hypoalgesia at basal state, and localized hyperalgesia after re-nociceptive challenge induced by intraplantar injections of complete Freund's adjuvant (CFA) as adults. Then we recorded baseline cardiovascular variables and 24-h responsiveness to an injection of CFA in the free-moving adult rats with telemetric technique.