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J Blanc

Publications and source records attributed to J Blanc.

At least 19 recordsLinked to original sources
PubMed2001

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.

Animals↗
PubMed2000

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.

Adrenergic beta-Agonists↗
PubMed2000

[Hepatobiliary cystadenoma with mesenchymal stroma: a hormone dependent tumor. Report of five cases with immunohistochemical study of hormone receptors].

Hepatobiliary cystadenomas with mesenchymal stroma are rare neoplasms, which occur only in females; they have a strong tendency to recur and a potential for malignant transformation. Microscopic features are characteristic but clinical findings are highly variable and laboratory data non specific. We report 5 cases with immunohistochemical study, showing the characteristics of mesenchymal stromal cells: myofibroblastic phenotype and expression of progesterone receptors in all cases and estrogen receptors in 3 out of 5 cases. These results point out the possible hormonal dependance of this tumor.

Adult↗
PubMed2000

[Contribution of the renin-angiotensin system to blood pressure variability in hyperthyroid rats].

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.

Angiotensin I↗
PubMed2000

[Activation of the renin-angiotensin system and blood pressure variability in rats].

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.

Adrenergic beta-Agonists↗
PubMed1999

Spontaneous inhibitors of factor VIII: kinetics of inactivation of human and porcine factor VIII.

Autoantibodies to factor VIII (FVIII)(spontaneous inhibitors) often inactivate FVIII in a complex fashion (type II inhibitors) as compared with alloantibodies (hemophilic inhibitors), which usually demonstrate second-order reaction kinetics (type I inhibitors). The infusion of porcine FVIII in patients with spontaneous inhibitors may give rise to anti-porcine FVIII antibodies. The purpose of this study was to determine whether these were type I or type II inhibitors. Plasma from 8 patients with spontaneous inhibitors and 6 patients with hemophilia with inhibitors were studied. Equal volumes of patient plasma and either pooled normal human plasma or porcine FVIII (Hyate-C) were incubated at 37 degrees C for 90 minutes. Aliquots were removed immediately after mixing and at 30-minute intervals and assayed for FVIII by using a two-stage method. The values for residual FVIII were log-transformed and plotted against the time of incubation, and the resultant curves were analyzed for goodness of fit (coefficient of determination, r2) by using linear and exponential equations. The values were examined by paired t tests; P values were two-tailed. Values are expressed as mean +/- SD. The titers of spontaneous inhibitors against human FVIII ranged from 2.6 to 416 Bethesda Units (BU), and those against porcine FVIII ranged from 0.7 to 47 BU. Samples were diluted so that the FVIII levels in the mixtures before incubation were similar: human, 0.44 U/ml; porcine, 0.47 U/ml; P = not significant. Four of the 8 patients with spontaneous inhibitors inactivated human FVIII in a fashion consistent with complex kinetics; their r2 values with the linear equation were less than 0.90. All r2 values improved when the exponential equation was used (linear, 0.90 +/- 0.08; exponential, 0.92 +/- 0.06; P = .007). In contrast, r2 values with porcine FVIII were the same (0.94) with either the linear or the exponential equation (P = not significant). r2 for the 6 hemophilic inhibitors showed no significant difference between the linear and exponential equations; the values were 0.99 with human FVIII and 0.95 with porcine FVIII. In non-hemophilic patients, antibodies developing to porcine FVIII have kinetics of inhibition that are second order (type I), even though antibodies to human FVIII in these same patients may have complex (type II) kinetics.

Animals↗
PubMed1999

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.

Animals↗
PubMed1998

[Autonomic contribution to the blood pressure and heart rate variability changes in early experimental hyperthyroidism].

A great deal of uncertainty persists regarding the exact nature of the interaction between autonomic nervous activity and thyroid hormones in the control of heart rate (HR) and blood pressure (BP). Thyrotoxicosis was produced by a daily intraperitoneal (i.p.) injection of L-thyroxine (0.5 mg/kg body wt in 1 ml of 5 mM NaOH for 5 days). Control rats received i.p. daily injections of the thyroxine solvant. Autonomic blockers were administered intravenously: atropine (0.5 mg/kg), atenolol (1 mg/kg), atenolol + atropine or prazosin (1 mg/kg). Eight animals were studied in each group. Thyroxine treatment was sufficient to induce a significant degree of tachycardia (423 +/- 6 vs 353 +/- 4 bpm; p < 0.001, unpaired Student's tests), systolic BP elevation (142 +/- 3 vs 127 +/- 2 mmHg; p < 0.001), pulse pressure increase (51 +/- 2 vs 41 +/- 2 mmHg, p < 0.01), cardiac hypertrophy (1.165 +/- 0.017 vs 1.006 +/- 0.012 g, p < 0.001), weight loss (-21 +/- 2 g; p < 0.001) and hyperthermia (37.8 +/- 0.1 vs 37.0 +/- 0.1 degrees C, p < 0.001). The intrinsic HR observed after double blockade (atenolol + atropine) was markedly increased after treatment with thyroxine (497 +/- 16 vs 373 +/- 10 bpm, p < 0.05). Vagal tone (difference between HR obtained after atenolol and intrinsic HR) was positively linearly related to intrinsic HR (r = 0.84; p < 0.01). Atenolol neither modified HR nor BP variability in rats with hyperthyrodism. The thyrotoxicosis was associated with a reduction of the 0.4 Hz component of BP variability (analyses on 102.4 sec segments, modulus 1.10 +/- 0.07 vs 1.41 +/- 0.06 mmHg; p < 0.01). Prazosin was without effect on this 0.4 Hz component in these animals. These data show a functional diminution of the vascular and cardiac sympathetic tone in experimental hyperthyroidism. Increased intrinsic HR resulting from the direct effect of thyroid hormone on the sinoatrial node is the main determinant of a tachycardia leading to a subsequent rise in cardiac output. The resulting BP elevation could reflexly induce a vagal activation and a sympathetic (vascular and cardiac) inhibition.

Animals↗
PubMed1997

Autonomic components of the cardiovascular responses to an acoustic startle stimulus in rats.

1. A loud acoustic stimulus was administered to rats prior to and after treatment with autonomic blockers in order to unravel the autonomic mechanisms of the blood pressure (BP) and heart rate (HR) responses to startle. 2. Six rats, implanted with a BP telemetric system, were used in a randomized crossover saline-controlled (saline vs. autonomic blocker) study with a washout period of 7 days between each active session. A first acoustic stimulus (110 dB, 0.7 s) was administered. An autonomic blocker i.e. atropine methylnitrate (15 mg. kg-1), atenolol (15 mg. kg-1) or prazosin HCl (1 mg. kg-1), or physiological saline was administered i.p. 40 min prior to a second identical acoustic stimulus. 3. The average BP rise following the first stimulus was +25 mmHg and the average HR change was +17 bpm. The responses after autonomic blockades were affected as follows: atropine increased the HR rise (+45.1 +/- 1.7 bpm), atenolol reversed the HR changes to a bradycardic response (-21.4 +/- 9.1 bpm), after prazosin treatment the BP rise was reversed into a BP decrease (-11.3 +/- 3.2 mmHg) and the HR increase was amplified (+76.0 +/- 10.0 bpm). Finally, the delay for obtaining the maximal BP change was increased from 1.9 to 2.6 s following prazosin pretreatment. 4. These results indicate that the BP rise resulting from an acute loud noise depends on a vascular sympathetic activation (prevented with prazosin), which is partly blunted by vasodilation (revealed with prazosin). The evoked HR changes combine a sympathetic activation (fully expressed following atropine) and a vagal activation (unmasked with atenolol). Further experiments are necessary to document the vasodilatory component unmasked with prazosin.

Acoustic Stimulation↗
PubMed1997

Social isolation affects the pattern of cardiovascular responses to repetitive acoustic startle stimuli.

1. The aim of this study was to investigate the cardiovascular responses to repetitive alerting stimuli in rats subjected to intermittent social isolation, in comparison with animals housed in pairs. 2. Ten male Wistar rats were implanted with a blood pressure (BP) telemetric system and enrolled in a randomized cross-over study design. Rats were either isolated or housed in pairs for an 8 day period. At the end of each period, the animals were exposed to five acoustic stimuli (110 dB at 15 kHz, 80 ms after the impact, duration 700 ms) at 60 s intervals. For each stimulus, maximal BP and heart rate (HR) responses were calculated. BP variability was analysed in the frequency domain before the first stimulation using power spectral analysis. 3. Isolated animals showed more faster breathing (1.71 vs 1.42 Hz in the paired condition). The 0.4 Hz zone of the systolic BP spectral power was not significantly affected by isolation (1.11 vs 0.85 mmHg2). BP and HR resting levels of isolated rats (121 mmHg for the systolic BP and 290 b.p.m.) were similar to those of animals housed in pairs (119 mmHg for the systolic BP and 279 b.p.m.). 4. The first acoustic stimulus caused a brief rise in BP of a comparable amplitude in both conditions (24 +/- 2 mmHg). A biphasic HR response was also observed, but the delayed bradycardia was more marked during isolation (37 vs 6 b.p.m. decrease). BP and HR levels were restored within 20 s. 5. Interestingly, BP responses were progressively attenuated to become negligible at the fifth presentation (1 mmHg) in the isolated state, while during the paired state a substantial pressor response (13 mmHg) after each successive stimulus was maintained. Paired rats exhibited a constant HR profile across the trials, consisting in a slight HR increase (< 5 b.p.m.), concomitant with the BP elevation, followed by a delayed bradycardia (around 15 b.p.m.). HR profiles in the isolated condition differed markedly: HR rises increased in magnitude with the trial number, reaching 30 b.p.m. after the 5th trial. 6. Spontaneous BP and HR increases, as observed throughout the experiment were quantitatively small (6 mmHg and < 10 b.p.m.) in the two conditions. 7. These data indicate that isolation markedly affects the BP habituation profile to repetitive alerting stimuli. The BP response attenuation might unmask a tachycardic response. Alternatively, the amplified tachycardia following the latter stimuli might express sensitization to the conditioned fear resulting from isolation.

Acoustic Stimulation↗
PubMed1996

Accuracy and mean duration of different protocols of head-up tilt testing.

Based on the results of our study, > 95% of patients with a positive passive tilt test are also positive during 3 micrograms/min, and especially 5 micrograms/min, isoproterenol tilt test. A proposed time-saving protocol would be to initiate the test with an isoproterenol infusion and to perform a 45-minute passive tilt only in those patients with a positive 5 micrograms/min (an infusion rate reported to have an excessive low specificity) isoproterenol tilt test, and to consider only those with symptoms associated with objective changes during this latter test as "finally positive." An alternative option would be to perform a 45-minute passive tilt only in those patients with a negative 3 micrograms/min isoproterenol tilt test.

Adolescent↗
PubMed1996

Contribution of the renin-angiotensin system to short-term blood pressure variability during blockade of nitric oxide synthesis in the rat.

1. The aim of this study was to investigate, by use of spectral analysis, (1) the blood pressure (BP) variability changes in the conscious rat during blockade of nitric oxide (NO) synthesis by the L-arginine analogue NG-nitro-L-arginine methyl ester (L-NAME); (2) the involvement of the renin-angiotensin system in these modifications, by use of the angiotensin II AT1-receptor antagonist losartan. 2. Blockade of NO synthesis was achieved by infusion for 1 h of a low-dose (10 micrograms kg-1 min-1, i.v., n = 10) and high-dose (100 micrograms kg-1 min-1, i.v., n = 10) of L-NAME. The same treatment was applied in two further groups (2 x n = 10) after a bolus dose of losartan (10 mg kg-1, i.v.). 3. Thirty minutes after the start of the infusion of low-dose L-NAME, systolic BP (SBP) increased (+10 +/- 3 mmHg, P < 0.01), with the effect being more pronounced 5 min after the end of L-NAME administration (+20 +/- 4 mmHg, P < 0.001). With high-dose L-NAME, SBP increased immediately (5 min: +8 +/- 2 mmHg, P < 0.05) and reached a maximum after 40 min (+53 +/- 4 mmHg, P < 0.001); a bradycardia was observed (60 min: -44 +/- 13 beats min-1, P < 0.01). 4. Low-dose L-NAME increased the low-frequency component (LF: 0.02-0.2 Hz) of SBP variability (50 min: 6.7 +/- 1.7 mmHg2 vs 3.4 +/- 0.5 mmHg2, P < 0.05), whereas the high dose of L-NAME not only increased the LF component (40 min: 11.7 +/- 2 mmHg2 vs 2.7 +/- 0.5 mmHg2, P < 0.001) but also decreased the mind frequency (MF: 0.2-0.6 Hz) component (60 min: 1.14 +/- 0.3 mmHg2 vs 1.7 +/- 0.1 mmHg2, P < 0.05) of SBP. 5. Losartan did not modify BP levels but had a tachycardic effect (+45 beats min-1). Moreover, losartan increased MF oscillations of SBP (4.26 +/- 0.49 mmHg2 vs 2.43 +/- 0.25 mmHg2, P < 0.001), prevented the BP rise provoked by the low-dose of L-NAME and delayed the BP rise provoked by the high-dose of L-NAME. Losartan also prevented the amplification of the LF oscillations of SBP induced by L-NAME; the decrease of the MF oscillations of SBP induced by L-NAME was reinforced after losartan. 6. We conclude that the renin-angiotensin system is involved in the increase in variability of SBP in the LF range which resulted from the withdrawal of the vasodilating influence of NO. We propose that NO may counterbalance LF oscillations provoked by the activity of the renin-angiotensin system.

Animals↗
PubMed1996

Role of angiotensin II and catecholamines in blood pressure variability responses to stress in SHR.

The contribution of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) to blood pressure (BP) and heart rate (HR) variability responses to air-jet stress was assessed in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Activity of the encogenous RAS was suppressed by chronic treatment by a nonpeptide angiotensin II receptor antagonist (Iosartan). The role of alpha 1-adrenoceptor activity was evaluated in rats by acute administration of prazosin. In untreated animals, an air jet induced an increase in systolic BP (SBP; 9 +/- 2 mmHg for WKY and 8 +/- 2 mmHg for SHR) and in HR (56 +/- 19 beats/min for WKY and 76 +/- 8 beats/min for SHR), followed by an increase of the midfrequency (MF; 0.2-0.6 Hz) component of HR in WKY (183%) and by an increase of the MF component of SBP and diastolic BP in SHR (65%). Prazosin prevented BP rises as well as the MF component of BP and HR increases associated with air-jet stress. Chronic suppression of the RAS by losartan did not alter the BP response to the air jet in WKY and slightly reduced it in SHR but abolished all the BP and HR variability changes in both strains. These results indicate that the SNS but not RAS is essential for the BP rise induced by stress and demonstrate that RAS in conjunction with SNS is involved in BP and HR variability changes associated with stress.

Angiotensin II↗
PubMed1996

[Contribution of the renin-angiotensin system to the variability of blood pressure in hypertensive rat after blockade of nitric oxide synthesis].

The aim of this study was to investigate, using spectral analysis, 1) the blood pressure (BP) variability changes in the conscious rat during blockade of nitric oxide (NO) synthesis by the L-arginine analogue L-NAME; 2) the involvement of the renin-angiotensin system in these modifications, using the angiotensin II AT1-receptor antagonist losartan. The blockade of the NO synthesis was made by infusion for 1 hour of a low dose (10 micrograms/kg/min, i.v.; n = 10) and a high dose (100 micrograms/kg/min, i.v.; n = 10) of L-NAME. The same treatment was applied in two further groups (n = 2 x 10) after a bolus of losartan (10 mg/kg, i.v.). The low dose of L-NAME increased systolic BP (SBP) on and after thirty min of infusion (+10 +/- 3 mmHg; p < 0.01). BP reached a maximum value 5 min after stopping L-NAME administration (+20 +/- 4 mmHg; p < 0.001). With the high dose of L-NAME, SBP increased immediately (5 min: +8 +/- 2 mmHg; p < 0.05) and reached a maximum at 40 min (+53 +/- 4 mmHg; p < 0.001); a bradycardia was observed (60 min: -44 +/- 13 batt/min; p < 0.01). The low dose of L-NAME increased the low-frequency component (LF: 0.02-0.2 Hz) of SBP variability (50 min: 6.7 +/- 1.7 mmHg2 vs 3.4 +/- 0.5 mmHg2; p < 0.05). The high dose of L-NAME increased the LF component (40 min: 11.7 +/- 2 mmHg2 vs 2.7 +/- 0.5 mmHg2; p < 0.001) and decreased the mid frequency (MF: 0.2-0.6 Hz) component (60 min: 1.14 +/- 0.3 mmHg2 vs 1.7 +/- 0.1 mmHg2, p < 0.05) of SBP. Losartan did not modify BP levels but had a tachycardic effect (+33 +/- 10 batt/min; n = 27). Moreover, losartan increased MF oscillations of SBP (4.26 +/- 0.49 mmHg2 vs 2.43 +/- 0.25 mmHg2; p < 0.001; n = 27). Losartan prevented the BP rise provoked by the low-dose of L-NAME and delayed the BP rise provoked by the high-dose. Losartan prevented the amplification of the LF oscillations of SBP induced by the L-NAME; the decrease of the MF oscillations of SBP induced by the L-NAME was reinforced after losartan). We concluded that the renin-angiotensin system is involved in the increase of variability of SBP in the LF range which resulted from the withdrawal of the vasodilatating influence of NO. We proposed that NO could counterbalance LF oscillations provoked by the activity of the renin-angiotensin system.

Angiotensin II↗
PubMed1995

Effects of losartan on short-term variability of blood pressure in SHR and WKY rats.

OBJECTIVE: to examine the effect of losartan on short-term variability of blood pressure (BP) in spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats. DESIGN AND METHODS: variability of BP was characterized during baseline condition and 20 minutes after blocking the renin-angiotensin system (RAS) with the AT1 receptor antagonist losartan (10 mg/kg, iv). A Fast Fourier Transform algorithm was used for analysis. RESULTS: under baseline conditions, SHR exhibited enhanced variability of BP compared to WKY, reflected by increased standard deviation (SD) of systolic BP (SBP). On the other hand, the mid frequency (0.2-0.6 Hz, MF) and the low frequency (0.02-0.2 Hz, LF) components of SBP were exaggerated. Enhanced MF area probably reflected a hyperactivity of the sympathetic nervous system in SHR. After a single injection of losartan, the mean BP was lowered in SHR by 13 +/- 5 mmHg, mean +/- SEM, P < 0.05). In WKY, losartan solely decreased the LF component of BP. In SHR, losartan increased the MF component of BP. CONCLUSION: losartan resulted in differential effects on BP variability in the two strains. In WKY, the RAS contributed to the genesis of LF fluctuations. In SHR, the increase in the MF component of BP after losartan probably indicated a reflex sympathetic activation triggered by vasodilation.

Animals↗
PubMed1994

Characterization of a promiscuous GTPase-activating protein that has a Bcr-related domain from Caenorhabditis elegans.

Human breakpoint cluster region (bcr) gene product is a member of a group of GTPase-activating proteins that act exclusively on members of the Ras-related Rho subfamily. A complementary DNA was isolated from Caenorhabditis elegans that encoded a polypeptide of 1438 amino acid residues, CeGAP, which contains a domain with sequence similarity to the COOH-terminal segment (GTPase-activating protein region) of Bcr and other known GTPase-activating proteins of the Rho subfamily. It also contains a "pleckstrin homology" motif, present in many signaling proteins including GTPase-activating proteins and nucleotide exchange factors. The Bcr-like domain of CeGAP exhibited activity not only on members of the C. elegans and human Rho subfamily but surprisingly also on C. elegans Ras protein (let-60), human Ras, and Rab3A. CeGAP is therefore the first GTPase-activating protein acting on Ras-related proteins across different subfamilies. Together with the presence of the pleckstrin homology motif, our finding suggests a central and integrative role for CeGAP in a signaling pathway common to Ras and related proteins.

Amino Acid Sequence↗
PubMed1994

Spectral analysis of blood pressure and heart rate variability in response to stress from air-jet in the Lyon rat.

1. Power spectral analysis of the frequency of wave-forms of blood pressure and heart rate was used to characterize short-term fluctuations of these parameters in three strains of conscious Lyon rat, normotensive (LL and LN) and hypertensive LH. 2. A mild stress produced by means of a jet of air elicited blood pressure rises, associated with tachycardia. This response was of similar magnitude in the three strains. The stressor amplified the medium frequency (195-605 mHz) Mayer waves of blood pressure and heart rate which are under autonomic control. 3. Clonidine (10 micrograms kg-1 i.v.) lowered blood pressure and heart rate and dramatically reduced the amplitude of blood pressure and heart rate oscillations in the frequency region of 195-605 mHz. 4. A jet of air applied after clonidine administration led to blood pressure rise associated with tachycardia and enhanced oscillations in the 195-605 mHz region. 5. These results indicate that in Lyon normotensive and hypertensive rats, a mild emotional stressor elicits blood pressure and heart rate rises associated with spectral modifications reflecting sympathetic hyperactivity. Clonidine lowers blood pressure and heart rate and reduces their related variabilities. This effect is more pronounced in LH rats than in their normotensive controls. Clonidine appears to reduce the autonomic response to stress as indicated by the medium frequency oscillations.

Analysis of Variance↗