[Short-term variability of blood pressure: physiology and pharmacology]. / Variabilité à court terme de la pression artérielle: physiologie et pharmacologie.

Non invasive continuous measurement of blood pressure (BP) is currently performed at the finger level. The various oscillations of BP are distinguished using spectral analysis based on the fast Fourier transform. The first order oscillation of BP is synchronous with the heart beat and generates pulsaltile changes in BP. Second order oscillations are generated by respiration and depend on intrathoracic pressure changes. They do not exceed few millimeters of mercury. Heart rate also oscillates with respiration. This respiratory sinus arrhythmia depends on vagal activity. A slower third order oscillation also called 10-s period rhythm or Mayer waves depend on vascular tone changes. These waves may reach 20 mmHg. Mayer waves reflect oscillations in resistance vessels and depend on sympathetic discharges. Sympathetic nerves determine oscillations in resistance vessels and cardiac rhythm at the same 0.1 Hz frequency. A better understanding of these oscillations helps in understanding BP regulatory mechanisms and in treating BP disorders. Prognosis of arterial hypertension also depends on these BP fluctuations. Recent time and frequency domain developments in the analysis of the reflex relationship between BP and heart rate allow the calculations of indexes of spontaneous baroreflex sensitivity. Baroreflex sensitivity is a new indicator of cardiovascular risk.

Glucose-induced insulin hypersecretion in lipid-infused healthy subjects is associated with a decrease in plasma norepinephrine concentration and urinary excretion.

We investigated the effect of a 48 h triglyceride infusion on the subsequent insulin secretion in response to glucose in healthy men. We measured the variations in plasma concentration and urinary excretion of catecholamines as an indirect estimation of sympathetic tone. For 48 h, 20 volunteers received a triglyceride/heparin or a saline solution, separated by a 1-month interval. At time 48 h, insulin secretion in response to glucose was investigated by a single iv glucose injection (0.5 g/kg(-1)) followed by an hyperglycemic clamp (10 mg.kg(-1).min(-1), during 50 min). The triglyceride infusion resulted in a 3-fold elevation in plasma free fatty acids and an increase in insulin and C-peptide plasma concentrations (1.5- and 2.5-fold, respectively, P < 0.05), compared with saline. At time 48 h of lipid infusion, plasma norepinephrine (NE) concentration and urinary excretion levels were lowered compared with saline (plasma NE: 0.65 +/- 0.08 vs. 0.42 +/- 0.06 ng/ml, P < 0.05; urinary excretion: 800 +/- 70 vs. 620 +/- 25 nmol/24 h, P < 0.05). In response to glucose loading, insulin and C-peptide plasma concentrations were higher in lipid compared with saline infusion (plasma insulin: 600 +/- 98 vs. 310 +/- 45 pM, P < 0.05; plasma C-peptide 3.5 +/- 0.2 vs. 1.7 +/- 0.2 nM, P < 0.05). In conclusion, in healthy subjects, a 48-h lipid infusion induces basal hyperinsulinemia and exaggerated insulin secretion in response to glucose which may be partly related to a decrease in sympathetic tone.

Impact of the renin-angiotensin system on cerebral perfusion following subarachnoid haemorrhage in the rat.

1. This study investigated the effects of blocking the AT1 angiotensin receptors with irbesartan, either peripherally or centrally, on systemic blood pressure, intracranial pressure and cerebral perfusion pressure following experimental subarachnoid haemorrhage (SAH) in urethane-anaesthetized rats. Sympathetic nervous activation was determined by measuring plasma noradrenaline levels. 2. In untreated animals, SAH induced a sustained increased in intracranial pressure from 2.1 +/- 0.3 to 16 +/- 2 mmHg (3 h, P < 0.001). Cerebral perfusion pressure was reduced by 20 % (P < 0.001), this reduction being maintained for 3 h. Sympathetic activation was evident in the high level of plasma noradrenaline measured 3 h post-SAH (751 +/- 104 vs. 405 +/- 33 pg ml(-1), P < 0.05). 3. Acute peripheral pretreatment with irbesartan (3 mg kg(-1), I.V.) prevented the rise in plasma noradrenaline and further aggravated the decrease in cerebral perfusion pressure by producing transient systemic hypotension (blood pressure was 85 +/- 6 mmHg at 2 h post-SAH vs. 100 +/- 3 mmHg, P < 0.01). 4. Intracisternal pretreatment with irbesartan (0.035 mg) did not prevent the rise in plasma noradrenaline post-SAH but enhanced the rise in intracranial pressure by 75 % compared with untreated animals. 5. This study demonstrates that peripheral endogenous angiotensin II interacts with the sympathetic nervous system in order to maintain an adequate cerebral perfusion following SAH. Endogenous angiotensin II in the brain seems to exert a protective effect by counteracting the elevation in intracranial pressure that occurs following experimental SAH.

Effects of drugs on the autonomic control of short-term heart rate variability.

The autonomic nervous system links the brain and the heart. Efferent links in the neural control of the heart consist of sympathetic and parasympathetic (vagal) fibers innervating the sinus node. Because sympathetic and vagal firing alter spontaneous sinus node depolarization, cardiac rate and rhythm convey information about autonomic influences on the heart. The easy availability of ECG rendered possible the assessment of sinus rhythm as an index of autonomic outflow. The frequency-domain approach uses non-invasive recordings and appears to provide a quantitative evaluation of the autonomic modulation of cardiovascular function. Spectral profiles resulting from vagal or sympathetic blockades at the cardiac (or vascular) level might be used as references to unravel the mechanism of action of the drug under examination. A more comprehensive assessment will be obtained if spectral analysis is used as a complement to existing techniques applied for describing the neurohumoral status of patients (microneurographic recordings, norepinephrine spillover). This review also reports some pitfalls encountered in variability studies.

Relationship between pulse interval and respiratory sinus arrhythmia: a time- and frequency-domain analysis of the effects of atropine.

Respiratory sinus arrhythmia (RSA) estimation is commonly used as a non-invasive index of cardiac vagal tone. To test this relationship, vagal tone was augmented or blocked using atropine. The study was carried out using 14 healthy volunteers, following beta-adrenoceptor blockade (10 mg bisoprolol per os) and during controlled respiration (0.25 Hz) in order to limit the confounding effects of cardiac sympathetic tone and respiration pattern changes. Atropine was slowly infused intravenously over a 30-min period up to a vagolytic cumulative dose of 0.04 mg/kg. The instant vagal tone was compared to the instant RSA value obtained from a time-/frequency-domain analysis of pulse interval (PI). RSA and PI varied in the same direction with an initial increase corresponding to the early vagomimetic effect of atropine followed by a decrease during the vagolytic phase. The comparative percentage fluctuations of RSA and PI over this large vagal tone range indicate that RSA is more sensitive (about twofold) than PI in reflecting fluctuations around the set point. This dissociated behaviour of PI and heart rate variability could be important to our understanding of the circulatory changes that result from fluctuations in vagal inputs to the sinus node.

Renin-angiotensin system contribution to cardiac hypertrophy in experimental hyperthyroidism: an echocardiographic study.

The objective of this study was to evaluate, using echocardiography, the involvement of the renin-angiotensin system (RAS) in left ventricular (LV) hypertrophy development in experimental hyperthyroidism. Thyrotoxicosis was produced by a daily intraperitoneal injection of L-thyroxine (T4), 0.1 mg/kg per day for 15 days in Wistar rats. Control (euthyroid) rats received intraperitoneal daily injection of the thyroxine solvent. Two series of experiments were performed. In the first series, euthyroid (n = 10) and hyperthyroid (n = 14) rats were surgically prepared with a femoral artery catheter. After a 3-day recovery period, blood pressure and heart rate were measured and blood samples were collected in conscious and unrestrained rats. In the second series of experiment, measurement of LV geometry was realized with two-dimensional time-movement echocardiography on the 15th day of treatment in control conditions and after long-term treatment with the angiotensin II type I receptor antagonist valsartan (10 mg/kg per day for 15 days) in both euthyroid and hyperthyroid rats. The dose and duration of T4 treatment was sufficient to induce a significant degree of hyperthyroidism with characteristic features including tachycardia, systolic hypertension, myocardial hypertrophy, hyperthermia, and weight loss. In addition, we measured an increase in free fractions of thyroid hormones, and a threefold increase in plasma renin activity. Echocardiographic examinations in rats revealed a strong correlation between LV weight and echocardiographic LV mass. Hyperthyroid rats exhibited an increased LV mass with a marked increase in the LV end-diastolic posterior wall and septal thickness. Chronic treatment with valsartan prevented this concentric LV hypertrophy (p < 0.01), with full prevention of the LV posterior wall hypertrophy (p < 0.001) and decreased LV septal hypertrophy (p < 0.05). In conclusion, the cardiovascular alterations of hyperthyroidism were reproduced with thyroid hormone injections in rats. Activation of the RAS in hyperthyroid rats was accompanied by increased LV mass. Using valsartan, we demonstrated that the RAS impinged on the LV remodelling in our experimental hyperthyroidism model. A chronic treatment with an angiotensin II type I receptor antagonist prevented the development of the concentric LV hypertrophy associated with thyrotoxicosis.

Subarachnoid haemorrhage-induced sympathoexcitation in rats is reversed by bosentan or sodium nitroprusside.

1. The roles played by nitric oxide (NO) and endothelin (ET) in the genesis of sympathetic nervous activation following experimental subarachnoid haemorrhage was investigated using spectral analysis of blood pressure rhythms. 2. Subarachnoid haemorrhage was induced in conscious rats by injecting 0.3 mL homologous blood via a catheter placed along the surface of the brain and directed towards the circle of Willis. Three hours after the insult and after sympathetic activation was evident, animals received either an acute injection of the ET antagonist bosentan (5 mg/kg, i.v.; n = 7), an infusion of the NO donor sodium nitroprusside (SNP; 18 microg/h; n = 7) or no treatment (n = 7). 3. Three hours following the induction of subarachnoid haemorrhage, the mid-frequency components of systolic blood pressure were markedly elevated, indicating a pronounced sympathoexcitation. However, blood pressure and heart rate levels remained unchanged at this time. In the absence of treatment, the mid-frequency components of blood pressure remained elevated for a subsequent 2 h. Treatment with a non-hypotensive dose of SNP reversed the sympathoexcitation within 1 h. Treatment with bosentan was also effective in reducing the mid-frequency oscillations in blood pressure associated with subarachnoid haemorrhage. 4. Our results indicate that subarachnoid haemorrhage is associated with an acute activation of the sympathetic nervous system. The degree of sympathoexcitation can be reversed by the use of either bosentan or SNP.

Antihypertensive monotherapy and cardiovascular responses to an acoustic startle stimulus.

To determine contribution of the autonomic nervous system to cardiovascular reactivity to noise, acoustic startle stimulus (110 dB, 1-20 kHz, 0.150 s) was administered to 35 subjects (19 women, 16 men) with mild essential hypertension. Among these patients, 10 were unmedicated and 25 were receiving long-term monotherapy (10 were taking 100 mg atenolol, 5 were taking 10 mg prazosin, and 10 were taking 50 mg losartan daily). Polygraphic recordings were obtained in supine position. Blood pressure (BP) and heart rate (HR) levels were stable until the noise was administered. In the unmedicated group BP and HR were elevated during the first 10 s. BP returned to resting levels after this period. The calculated hemodynamic indexes showed a biphasic change in total peripheral resistance (TPR), with an overall vasoconstriction associated with the BP rise phase, preceding a delayed vasodilation. The lowest HR changes were observed in the beta-blocker group with increases of 6 beats/min and 3 beats/min after the first and second noise stimulations, compared with 10 beats/min and 5 beats/min in the unmedicated group. Prazosin significantly reduced the BP rises to 7 mm Hg and 6 mm Hg for systolic BP and diastolic BP after the first stimulation compared with 22 mm Hg and 17 mm Hg in the untreated group (p < 0.01). The second stimulation after prazosin determined -5 mm Hg and 1 mm Hg changes for systolic BP and diastolic BP respectively, compared to rises of 13 mmHg for systolic BP and 10 mmHg for diastolic BP in the untreated group (p < 0.01). The hemodynamic percentage changes resulting from the first stimulation indicated prazosin markedly reduced the noise-induced rise in TPR (p < 0.05). No effect of beta-blocker was detectable using percentage changes. The rises in BP were amplified in the losartan-treated subjects compared with the other groups. Because of a low resting TPR in this group, the percentage changes in TPR resulting from noise were amplified in the subjects treated with the AT1 receptor antagonist. In conclusion the acoustic startle stimulus appeared as a simple and reliable procedure for inducing transient increases due to a rise in TPR. Cardiovascular responses differed according to the antihypertensive monotherapy, with a limited effect of noise in the prazosin-treated group.

Genetic influences on cardiovascular responses to an acoustic startle stimulus in rats.

1. The aim of the present study was to assess the cardiovascular differences among five inbred rat strains (n=16 per strain), including spontaneously hypertensive rats (SHR), Wistar Kyoto (WKY) rats, Wistar Furth (WF) rats, Fischer (F344) rats and Lewis (Lew) rats and the usual outbred Wistar (W) rat strain (n=25). 2. These strains were compared under resting conditions for blood pressure (BP) and heart rate (HR) levels and for their baroreceptor-HR reflex sensitivity. In addition, their responses to an acoustic startle stimulus were measured. 3. A consistent rise in BP was observed among the groups as a result of the noise stimulus. This rise in systolic BP (SBP) averaged (+/-SEM) 37 +/- 2 mmHg in the SHR and 34 +/- 4 mmHg in F344 rats, while the response was only 23 +/- 3 mmHg in WKY rats. Pulse pressure (PP) was increased following noise in all groups. The delay for the BP response for all groups combined was 1.6 +/- 0.1 s. 4. Most animals had minimal HR variations, except F344 rats, responding with a 42 +/- 13 b.p.m. decrease 3.0 s after the stimulus (i.e. 1.3 s after the maximal 34 +/- 4 mmHg SBP rise). 5. The highest SBP (160 +/- 3 mmHg) and diastolic BP (104 +/- 3 mmHg) were observed in inbred SHR. Other groups were normotensive. Resting PP was elevated for SHR (56 +/- 2 mmHg) compared with the other groups (40 +/- 2 mmHg). The highest HR was found in F344 and WF rats, with 389 +/- 11 and 372 +/- 7 b.p.m., respectively. The lowest HR was observed in SHR and Lewis rats, with 335 +/- 7 and 323 +/- 7 b.p.m., respectively. The least sensitive baroreflex function was observed in SHR (0.8 +/- 0.1 b.p.m./mmHg) compared with the other strains (1.4 +/- 0.2 b.p.m./mmHg). 6. The present study confirms the importance of genetic factors on the cardiovascular responses of rats to a noise startle stimulus. Two inbred normotensive rat strains, namely F344 and WKY rats, which exhibit a substantial difference in pressor response to noise, may be used to unravel the mechanisms of sympathetic activation.

Time- and frequency-domain estimation of early diabetic cardiovascular autonomic neuropathy.

The risk related to cardiovascular autonomic neuropathy dysautonomia should lead to a specific assessment of this complication of diabetes. The aim of this study was to estimate the accuracy of a battery of blood pressure (BP) and heart rate (HR) variability indexes obtained in different subgroups of diabetic subjects classified according to the conventional laboratory autonomic function tests (Ewing scores). Blood pressure was measured continuously at the finger level with a Finapres monitor while subjects were in the supine position and again while they were standing. Pulse intervals were derived from BP recordings and were taken as surrogates for R-R intervals. Subjects with borderline or definite cardiovascular autonomic neuropathy showed a similar degree of alterations of both HR and BP variability (spectral measures) and in the relationship between BP and HR (cross-spectral and sequence analysis). Subjects with no evidence of cardiovascular autonomic neuropathy on the basis of the conventional tests showed an altered relationship between BP and HR. This baroreceptor-HR reflex dysfunction could represent an early stage of cardiovascular autonomic neuropathy undetected by the conventional tests. The areas under the receiver operating characteristic plots indicated that the high-frequency peak of pulse interval was highly discriminant in the supine and standing positions. The cross-spectral analysis showed the best discrimination for the gain in the high-frequency range. For the sequence analysis, the slope was the best discriminant factor for any degree of cardiovascular autonomic neuropathy. In conclusion, these estimates of baroreceptor-HR function may provide a powerful tool for assessing cardiovascular autonomic neuropathy at any stage, including the early stage, which is not detected by the conventional tests.

[Baroreflex failure syndrome: an uncommon case of an extreme blood pressure variability]. / L'insuffisance du baroréflexe: un cas exceptionnel de variabilité tensionnelle extrême.

INTRODUCTION: The arterial baroreflex operates in physiological conditions. It induces sympathetic and vagal activity modulation resulting in arterial tone and heart rate changes. These appropriate responses limit blood pressure fluctuations and blood pressure is therefore regulated since the baroreflex constantly buffers the changes. EXEGESIS: Bilateral carotid body tumor excision resulted in excessive fluctuations of blood pressure. Indices of spontaneous baroreflex activity were markedly altered in the patient described herein. CONCLUSION: The excessive fluctuations of blood pressure due to the sinoaortic denervation demonstrate how powerful is this negative feedback control mechanism in control conditions.

Assessment of autonomic cardiovascular changes associated with recovery from anaesthesia in children: a study using spectral analysis of blood pressure and heart rate variability.

Recovery from anaesthesia is associated with large changes in cardiovascular autonomic activity, which are poorly documented in children. This study was undertaken to investigate the cardiovascular autonomic activity in anaesthetized and recovering children, using a noninvasive approach based on spectral analysis of heart rate (HR) and blood pressure (BP) variability. Ten children (aged 5-13 years) undergoing major surgery were studied. Continuous HR and BP were recorded using a noninvasive device during deep anaesthesia and recovery. Spectral analysis was used to determine the main oscillatory components of HR and BP signals. For each power spectrum, the frequency components were identified as follows (i): the low frequency (LF) component (0.04-0.14 Hz) both parasympathetically and sympathetically mediated for HR and corresponding to vasomotor sympathetic modulation for BP; and (ii) the high frequency (HF) component (0.2-0.6 Hz) parasympathetically mediated for HR, and reflecting mechanical influence of ventilation on cardiac output for BP. In addition, the LF : HF ratio for HR, reflecting the cardiac sympathovagal balance, was calculated. Under deep anaesthesia, HR variability and BP variability were very low and mainly due to mechanical influence of intermittent positive pressure ventilation. Conversely, the recovery period was associated with a marked increase of HR and BP overall variability. Compared to anaesthesia, spectral analysis of HR and BP revealed that the LF component of BP and HR spectra increased 40-fold during recovery; the LF : HF ratio of HR was also increased during recovery (0.1 +/- 0.1 versus 1.3 +/- 1.2, P=0.008). The results of this study demonstrate that the recovery period is associated with an increase of cardiovascular sympathetic drive in children after major surgery.

[Contribution of the renin-angiotensin system to blood pressure variability in hyperthyroid rats]. / Contribution du système rénine-angiotensine à la variabilité tensionnelle du rat hyperthyroïdien.

OBJECTIVES: To produce a chronical thyrotoxicosis model in rat, and to evaluate, using spectral analysis, the involvement of the renin-angiotensin system (RAS) in short-term variability of blood pressure (BP) in experimental hyperthyroidism. DESIGN AND METHODS: Thyrotoxicosis was produced by a daily intraperitoneal (i.p.) injection of L-thyroxine (T4: 0.1 mg/kg for 15 days) in Wistar rats. Control (euthyroid) rats received i.p. daily injection of the thyroxine solvent. Two series of experiments were performed in conscious and unrestrained rats. In the first series, 10 euthyroid and 14 hyperthyroid rats were surgically prepared with a femoral artery catheter to measure BP and heart rate (HR) and to collect blood samples on the last day of treatment. In the second series of experiments (n = 12 in each group), on the fifteenth day of treatment, BP and HR were recorded by telemetry in control conditions and after a specific blockade of the RAS by the angiotensin type I receptors antagonist: valsartan (10 mg/kg, i.p.). BP recordings were analysed by the Fast Fourier Transform on consecutive 204.8-s stationary periods. RESULTS: The dose and duration of T4 treatment was sufficient to induce a significant degree of hyperthyroidism with characteristic features including: tachycardia, systolic hypertension, myocardial hypertrophy, hyperthermia, and weight loss. In addition, we measured an increase in free fractions of thyroid hormones, and a 3 fold-increase of plasma renin activity. Hyperthyroidism modified systolic BP (SBP) variability profiles. An amplification of low frequency (LF) oscillations (2.37 +/- 0.12 mmHg vs 1.78 +/- 0.11 mmHg, p < 0.01) was observed after T4 treatment. In hyperthyroid rats, valsartan diminished the slow fluctuations of SBP (p < 0.001) and increased the mid-frequency oscillations (2.44 +/- 0.20 mmHg vs 1.32 +/- 0.18 mmHg, p < 0.001). CONCLUSION: The cardiovascular alterations of hyperthyroidism are reproduced with thyroid hormone injections in rats. Activation of the RAS in hyperthyroid rats was accompanied by increased SBP variability in the LF range. Using the angiotensin type I receptors antagonist, valsartan, we demonstrated that the RAS impinged on the LF oscillations of the SBP in our experimental hyperthyroidism model.

[Activation of the renin-angiotensin system and blood pressure variability in rats]. / Activation du système rénine-angiotensine et variabilité tensionnelle du rat.

This study was designed to assay, using spectral analysis, the influence of the renin-angiotensin system activation on the blood pressure variability. Rats were surgically prepared with a supra-renal catheter inserted via the left carotid artery to perform local infusions and with a femoral artery catheter to measure blood pressure (BP) and heart rate (HR). The beta-adrenoceptors stimulation by isoprenaline was used to increase the plasma renin activity (PRA). A first group (n = 8) was infused with isoprenaline (0, 0.003, 10, 100, 300 ng/kg/min) at a rate of 20 microL/min. A second group (n = 8) received a bolus of the angiotensin II (AII) AT1 receptor-antagonist valsartan (2 mg/kg/mL, i.a.) prior to isoprenaline infusions. Five groups were used for blood sampling (one group infused with one concentration of isoprenaline) to assay PRA and catecholamines (CA). BP recordings were analysed using the fast Fourier transforms (FFT) on 2048 points time series (204.8 s). Isoprenaline from the concentration of 10 ng/kg/min increased PRA with a maximum effect of 8.5 fold with the highest concentration (300 ng/kg/min, p < 0.05); CA were not modified. Isoprenaline amplified the low-frequency (LF: 0.02-0.20 Hz) component of the systolic BP (SBP) variability (10 ng/kg/min: 4.16 +/- 0.62 mmHg2 versus: 2.90 +/- 0.44 mmHg2 for control value, p < 0.05) even if it did not modify BP and HR levels. Isoprenaline lowered BP and had a tachycardic effect at concentrations > or = 100 ng/kg/mL (at 100 ng/kg/mL: SBP = 115 +/- 3 mmHg, HR = 464 +/- 15 bpm, versus control: SBP = 128 +/- 3 mmHg, HR = 351 +/- 7 bpm, p < 0.05). Valsartan modified neither BP levels nor BP variability but exerted a tachycardic effect (+25 bpm, p < 0.001). Valsartan prevented the amplification of the LF oscillations of SBP induced by isoprenaline (10 ng/kg/min: 2.53 +/- 0.38 mmHg2 versus: 2.20 +/- 0.25 mmHg2 for control value (valsartan), ns). We conclude that a moderate endogenous production of renin increases SBP variability in the LF range in the conscious rat. This effect which does not affect BP and HR levels is mediated by AII AT1 receptors and does not involve the sympathetic nervous system.

Endogenous renin and related short-term blood pressure variability in the conscious rat.

This study was designed to investigate, by use of spectral analysis, the blood pressure variability changes induced in the conscious rat by activation of plasmatic renin activity. Rats were surgically prepared with a supra-renal catheter inserted via the left carotid artery to perform the infusions, and with a femoral artery catheter to measure blood pressure and heart rate. Secretion of renin was induced using beta-adrenoceptor stimulation produced by isoprenaline. A first group (n=8) was infused with isoprenaline: 0.003, 10, 100 and 300 ng/kg/min, at a rate of 20 microl/min. A second group (n=8) was given a bolus injection of the angiotensin AT(1) receptor antagonist, valsartan (2 mg/kg, i.a.), prior to isoprenaline infusions. The lack of effect of infusion per se was checked in additional animals (n=8) infused with saline only (20 microl/min). Five other groups of animals were prepared with arterial catheters as mentioned previously. Each group received one concentration of infused isoprenaline and samples of blood were collected for further determinations of plasma renin activity and catecholamine concentrations. Blood pressure recordings were analysed using the fast Fourier transform on 2048 points time series (204.8 s). Isoprenaline increased plasma renin activity and did not modify plasma catecholamine concentrations. The low-frequency (0.02-0.2 Hz) component of the systolic blood pressure variability was amplified by isoprenaline (10 ng/kg/min isoprenaline: 4.16+/-0.62 mm Hg(2) vs. 2.90+/-0.44 mm Hg(2) for control value, P<0.05), a concentration that did not alter either blood pressure or heart rate levels. Isoprenaline lowered blood pressure and increased heart rate, starting at concentrations of 100 ng/kg/min. Valsartan, whose principal effect was generation of tachycardia (+25 bpm) modified neither blood pressure levels nor blood pressure variability. Valsartan prevented the amplification of the low-frequency oscillations of systolic blood pressure induced by isoprenaline (10 ng/kg/min isoprenaline: 2.53+/-0.38 mm Hg(2) vs. 2.20+/-0.25 mm Hg(2) for control value (valsartan, ns). We conclude that a moderate increase of plasma renin activity enhanced systolic blood pressure variability in the low-frequency range, without affecting blood pressure and heart rate levels.

Early detection of cardiovascular autonomic neuropathy in diabetic pigs using blood pressure and heart rate variability.

Cardiac autonomic neuropathy is a common complication in insulin dependent diabetes mellitus. Nevertheless, little is known about when this impairment occurs during the time course of the disease. Analysis of blood pressure (BP) and heart rate (HR) variability could be used to detect early signs of autonomic alteration. To test this proposal, twelve sexually mature male Yucatan miniature pigs were equipped with an arterial catheter for telemetric BP analysis, and with a venous access. BP and HR were recorded together with respiratory movements while the animals were resting in a sling. After the first recording session performed when the pigs were 5 months old, streptozotocin (STZ) was used to induce diabetes in seven pigs, while the five others were controls. BP and HR were measured 3 and 6 months after the onset of diabetes and at a similar age in the controls. BP and HR oscillated at the respiratory range (0.19 Hz). Spectral analysis showed this respiratory component was the main determinant of the short-term variability of BP and HR. Atropine increased HR and BP and markedly diminished the respiratory sinus arrhythmia. Propranolol diminished HR and the respiratory peak of HR. A reduced respiratory oscillation of BP paralleled the diminution of the respiratory peak of HR. Baroreceptor-HR reflex was estimated using injections of phenylephrine and nitroprusside, and by cross-spectral analysis between BP and HR. Atropine shifted the curve to higher HR values, while propranolol reduced the level of the upper plateau. Atropine decreased both the coherence and gain of the cross-spectral analysis. STZ injection resulted in a type 1 diabetes. At 3 months, diabetic pigs exhibited low levels of BP and a reduced overall variability of HR and BP. Spectral analysis indicated the respiratory sinus arrhythmia was markedly reduced. In addition, the sensitivity of the baroreceptor-HR reflex was reduced. At a latter stage of diabetes these alterations were marked and the level of the resting HR was increased. These data demonstrate the dual (vagal and sympathetic) control of HR in pigs and the dominant role of respiration in the genesis of HR and BP fluctuations. The spectral and cross-spectral analysis of BP and HR were altered after 3 months of diabetes and could be proposed as early detectors of cardiac autonomic neuropathy.

Subarachnoid hemorrhage induced sympathoexcitation arises due to changes in endothelin and/or nitric oxide activity.

OBJECTIVE: The demonstration of the effectiveness of endothelin antagonists and nitric oxide donors in managing vasospasm following subarachnoid hemorrhage is encouraging. Whether such drugs can modify the sympathoexcitation that accompanies this condition remains unknown and was the basis for the present report. METHODS: Subarachnoid hemorrhage was induced in conscious rats by injecting blood via a catheter placed along the surface of the brain and directed towards the circle of Willis. We combined measurements of arterial plasma catecholamines with the spectral analysis of blood pressure variability in order to examine sympathetic nervous activation following subarachnoid hemorrhage. Experiments were performed in untreated animals and in rats following pretreatment with either bosentan or sodium nitroprusside. RESULTS: Indicative of a pronounced sympathoexcitation, the 0.2-0.6 Hz frequency components of blood pressure were markedly elevated following subarachnoid hemorrhage (2.5 +/- 0.5 vs. 8.9 +/- 2.6 mmHg2, P < 0.01). Parallel changes in plasma norepinephrine concentration were observed (1.0 +/- 0.2 vs. 2.4 +/- 0.4 nmol/l, P < 0.01). The subarachnoid injection of saline did not modify blood pressure variability or plasma norepinephrine concentrations. Pretreatment with either bosentan or sodium nitroprusside completely prevented the subarachnoid hemorrhage induced sympathoexcitation. CONCLUSIONS: Experimental subarachnoid hemorrhage is associated with a pronounced activation of the sympathetic nervous system. It would appear that this sympathoexcitation has its roots ensconced in either the release of endothelin or an impairment in nitric oxide mediated vasodilation.

[The autonomic nervous system and hypertension: quid novi?]. / Le système nerveux autonome en hypertension artérielle: quid novi?

Recent publications concerning the role of the autonomic nervous system in hypertension have demonstrated the nature of spontaneous oscillations of the blood pressure. The contribution of sympathetic stimulations indicates the baroreflex nature of certain rhythms, which opens a perspective of understanding the relations between increased sympathetic activity and hypertension. The sympathetic nervous system, angiotensin II and aldosterone are related, and antihypertensive therapy may therefore target one or the other, providing that the regulating functions are maintained. These concepts are developed in a recent series of articles which are presented schematically in this update.

Blood pressure variability in established L-NAME hypertension in rats.

METHODS: Blood pressure variability was evaluated in conscious Wistar control rats and rats with established L-NAME hypertension (20 mg/kg per 24 h, 4 weeks). RESULTS: Final systolic arterial pressure was 185+/-5 and 132+/-4 mm Hg in the Nomega-nitro-L-arginine methyl ester (L-NAME)-treated and control rats, respectively. The standard deviation of systolic arterial pressure in the L-NAME group was 70% greater than in the control rats, indicating a significant increase in the overall variability. Arterial pressure in the L-NAME rats exhibited aperiodical, abrupt rises and falls and data was grossly non-stationary. Blood pressure variability was therefore evaluated using Poincaré plot analysis. The variance of the difference (delta) between two successive values of systolic arterial pressure, determined for time intervals of 0.2 to 5 s (0.2 s increment), was always significantly higher in the L-NAME group compared with untreated animals. The variance of delta systolic arterial pressure increased with the time interval and plateaued for time intervals of 2.4 and 1.4 s in hypertensive and normotensive rats, respectively. These differences vanished when the sudden events oberved in L-NAME rats were omitted in the construction of Poincaré plots. Acute administration of prazosin (1 mg/kg), but not losartan (10 mg/kg) markedly reduced the variance of delta systolic arterial pressure in hypertensive rats. CONCLUSIONS: Nitric oxide participates in the control of arterial pressure variability. The sympathetic nervous system seems to be a major determinant of the increased short-term variability of arterial pressure in this model.

Beneficial effect of renin-angiotensin system for maintaining blood pressure control following subarachnoid haemorrhage.

Subarachnoid haemorrhage is a serious condition often accompanied by delayed cerebral ischaemia. Earlier reports have provided evidence suggesting a role for angiotensin II in the development of cerebral vasospasm following subarachnoid bleeding. We sought to examine the influence of angiotensin II blockade with losartan on blood pressure and survival in animals following experimental subarachnoid haemorrhage, induced in conscious rats by injecting homologous blood via a catheter placed along the surface of the brain. We combined measurements of plasma renin activity with blood pressure recording in order to examine renin-angiotensin system activation following experimental subarachnoid haemorrhage. Following subarachnoid injury an approximately three-fold increase in plasma renin activity occurred (3.4 +/- 1.0 vs. 10.1 +/- 1.8 ng angiotensin I produced/ml/h, p < 0.01). In animals treated with losartan (20 mg/kg) prior to the induction of subarachnoid haemorrhage blood pressure fell dramatically following the cerebral injury (124 +/- 5 vs. 94 +/- 7 mmHg, p < 0.001), whereas blood pressure remained unchanged in control animals. Survival was markedly reduced in those animals treated with losartan. Given the pronounced decrease in blood pressure and impaired survival following subarachnoid haemorrhage in animals treated with losartan, it would appear that the acute activation of the renin-angiotensin system following this insult is in fact a desirable, compensatory response.