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Biomedical subjects

Jean-Luc Elghozi

Publications and source records attributed to Jean-Luc Elghozi.

12 recordsLinked to original sources

Nitric oxide pathway counteracts enhanced contraction to membrane depolarization in aortic rings of rats on high-sodium diet.

Vascular smooth muscle cell contraction and endothelium-dependent relaxation was evaluated in aortic rings isolated from weaned, 5-mo-old Sprague-Dawley rats fed a normal (NS; 0.8% NaCl) or high (HS; 8% NaCl) sodium diet. Arterial pressure was 140 +/- 6 (NS) and 145 +/- 6 mmHg (HS). In endothelium-denuded rings, the response to phenylephrine (PE) was not modified by the sodium diet, while that of depolarizing agent KCl and intracellular calcium releasing agent caffeine increased in the HS group. When endothelium was preserved, PE-evoked contraction was reduced in both NS and HS groups, the contraction being yet lower in the HS group. This effect was partially obliterated by addition of N(G)-nitro-L-arginine methyl ester (L-NAME), independently of the sodium diet. Relaxation to ACh in intact rings and to sodium nitroprusside (SNP) and 8-bromoadenosine 3'5' cyclic guanosine monophosphate (8-BrcGMP) in the absence of endothelium was enhanced in rings isolated from HS rats. In addition, the dose-response curve to 8-BrcGMP was shifted to the right in the presence of iberiotoxin, an inhibitor of large conductance, voltage-dependent, and calcium-sensitive potassium channel (BK(Ca)). However, shift was more marked in rings from HS rats. Present results provide evidence that response of vascular smooth muscle cell to nitric oxide/cGMP-related compounds is increased in HS rings and is associated with a greater activation of the repolarizing BK(Ca) channels. Such changes might counterbalance enhanced contractile response to membrane depolarization and thus participate in maintenance of arterial pressure in the present model of early and long-term HS feeding in rats.

Acetylcholine↗

Optimal frequency ranges for extracting information on cardiovascular autonomic control from the blood pressure and pulse interval spectrograms in mice.

The analysis of blood pressure (BP) and heart rate (HR) variability by spectral methods has proven a useful tool in many animal species for the assessment of the vagal and sympathetic contributions to oscillations of BP and HR. Continuous BP measurements obtained in mice by telemetry were used to characterize the spectral bandwidths of autonomic relevance by using an approach with no a priori. The paradigm was based on the autonomic blockades obtained with conventional drugs (atropine, prazosin, atenolol). The spectral changes were estimated in all of the combinations of spectral bandwidths. The effect of hydralazine was also tested using the same systematic analysis, to detect the zones of sympathetic activation resulting reflexly from the vasodilatory action of the drug. Two zones of interest in the study of the autonomic control of BP and HR were observed. The first zone covered the 0.15-0.60 Hz range of the systolic BP spectrum and corresponds to the low-frequency zone (or Mayer waves). This zone reflects sympathetic control since the power spectral density of this zone was significantly reduced with alpha1-adrenoceptor blockade (prazosin), while it was significantly amplified as a result of a reflex sympathetic activation (hydralazine). The second zone covered the 2.5-5.0 Hz range of the pulse interval spectrum and corresponded to the high-frequency zone (respiratory sinus arrhythmia) under vagal control (blocked by atropine). These zones are recommended for testing the autonomic control of circulation in mice.

Animals↗

Effects of rilmenidine on 24-h rhythmicity of blood pressure and spontaneous baroreflex sensitivity in essential hypertensive subjects.

OBJECTIVE: To study the effects of the centrally acting imidazoline-like compound rilmenidine on the circadian and short-term cardiovascular rhythms derived from continuous blood pressure (BP) recordings in patients with mild essential hypertension. METHODS: This was a single-center, open study. Recordings were obtained from eight subjects, using a Portapres during two 24-h hospitalizations: the first after the inclusion visit and the second 4 weeks after starting rilmenidine treatment (1 or 2 mg/day). For circadian analysis of cardiovascular variables, 10 min were selected every hour to obtain 24 periods per subject for each session. Spontaneous baroreflex sensitivity (BRS) was estimated using the sequence technique and the cross-spectral analysis between systolic BP and interbeat intervals. RESULTS: Rilmenidine significantly reduced the overall systolic and diastolic BP and heart rate (P < 0.001). The effects of rilmenidine on BP and heart rhythm were marked during the daytime. Rilmenidine reduced the low-frequency (LF) component of systolic BP variability throughout the 24 h. The highest values of spontaneous BRS were observed at night. Rilmenidine increased the BRS obtained by the slope of the sequence method throughout the 24-h period (P < 0.001). The LF gain was significantly increased with rilmenidine during the day and the night. CONCLUSIONS: Rilmenidine may differentially affect the baroreflex-dependent (phasic or reflex) and the baroreflex-independent (tonic) autonomic outflow. The 24-h approach reinforced this concept, since indexes of BRS were increased throughout the 24-h period while BP was reduced during the daytime.

Adult↗

Short-term blood pressure and heart rate variability in congenital central hypoventilation syndrome (Ondine's curse).

The effect of CCHS (congenital central hypoventilation syndrome, or Ondine's curse) on short-term BP (blood pressure) and HR (heart rate) variability was evaluated in 16-year-old subjects presenting a form of CCHS requiring night ventilatory assistance. The 12 patients were compared with 12 age- and gender-matched healthy volunteers. Recordings were obtained during daytime while the subjects were breathing spontaneously. Continuous BP was measured with a Finapres device in the supine, head-up tilt and standing positions. The manoeuvre of actively standing was also analysed. HR levels were elevated in CCHS subjects at supine rest (+23%) with a reduced HR overall variability (-88%). The low- and high-frequency components of HR variability were affected. BP levels were preserved at rest, but the manoeuvres demonstrated a limited capacity to elevate BP. There was no overshoot in BP during the manoeuvre of actively standing, and steady standing BP levels in patients were not higher than supine BP levels as usually observed in healthy controls. The spontaneous baroreflex sensitivity estimated using the sequence technique or the cross-spectral analysis fell in the patients to approx. one-third of the sensitivity estimated in the healthy controls whatever the position. This cardiovascular profile suggests a predominant vagal dysfunction with signs of vagal withdrawal and baroreflex failure, and relative preservation of the cardiac and vascular sympathetic function. It is likely that the impaired ontogeny of the visceral reflexes, considered now to cause CCHS syndrome, includes the baroreceptive pathway and mainly its vagal component.

Adolescent↗

Stroke volume monitored by modeling flow from finger arterial pressure waves mirrors blood volume withdrawn by phlebotomy.

Rate-controlled blood withdrawal was used to reduce cardiac preload and consequently stroke volume in patients with normal cardiac function. Twelve patients with asymptomatic hereditary hemochromatosis, undergoing regular phlebotomy therapy, volunteered for the study. An average volume of 375 ml was withdrawn in an average period of 6.4 min. Finger pressure was continuously measured by a Finometer device which includes the Beatscope software for deriving the stroke volume from the blood pressure waveform. Blood withdrawal resulted in reduction of the stroke volume estimates (from 94.0 +/- 5.2 to 80.7 +/- 5.3, P < 0.05) together with a reduced pulse pressure (from 53.0 +/- 3.5 to 47.1 +/- 3.2, P < 0.05). No significant changes in heart rate (75.2 +/- 3.7 versus 78.3 +/- 4.5 beats/min) were observed. Calculated cardiac output was reduced while calculated total peripheral resistance was elevated after blood withdrawal. Beat-to-beat analysis demonstrated a significant linear regression between most of the hemodynamic indices and the volume withdrawn. The highest correlation coefficients were found for the stroke volume (0.88 +/- 0.01, P < 0.001) and the pulse pressure (0.80 +/- 0.04, P < 0.001) corresponding also to the highest slopes for the lines relating these measures to the relative blood volume withdrawn. The non-invasive estimation of finger blood pressure can be used to derive simple on-line indices (pulse pressure, stroke volume using the Modelflow) of cardiac preload, which are of major interest in the monitoring of cardiovascular status.

Adult↗

Contrasting circadian rhythms of blood pressure among inbred rat strains: recognition of dipper and non-dipper patterns.

OBJECTIVE: The non-dipper pattern, i.e. the lack of nocturnal blood pressure (BP) fall, carries a high risk of cardiovascular complications, both in hypertensive and normotensive subjects. Without genetic engineering, experimental demonstration of the non-dipper phenomenon is lacking. The purpose of this study was to assess the haemodynamic and behavioural daily parameters among various strains of rats - spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) and Fischer 344 (F344) - in order to characterize their circadian patterns and to detect a non-dipper animal model. METHODS: Changes in BP, heart rate (HR), and spontaneous locomotor activity (SLA) were recorded continuously for 11 days using telemetry in freely moving 10-week-old male SHR, WKY and F344 rats, in standardized laboratory conditions. Variations in haemodynamic and behavioural parameters were assessed in terms of day/night differences and spectral power corresponding with the 24-h period. RESULTS: All rats exhibited clear circadian variations in HR and in SLA, in synchrony with the light cycle. Light/dark differences in BP were significantly lower in F344 compared with those of SHR and WKY. The smaller circadian changes in BP observed in F344 were also demonstrated using spectral analysis: the peak detected at 24-h was reduced in F344 compared with SHR and WKY. CONCLUSION: The inbred F344 strain lacks the typical circadian BP rhythm while oscillations of HR and SLA are maintained, suggesting different regulatory mechanisms. The F344 strain may represent a useful animal model for studying the effects of drugs aimed at restoring the dipper status.

Animals↗

Comparison of angiotensin II-induced blood pressure and structural changes in Fischer 344 and Wistar Kyoto rats.

1. The purpose of the present study was to evaluate the blood pressure (BP) response, the BP and heart rate (HR) components of the startle reaction and the structure of the carotid artery and the aorta during chronic infusion of angiotensin (Ang) II in Fischer 344 (F344) compared with Wistar Kyoto (WKY) rats, two in-bred normotensive contrasted strains. 2. Osmotic mini-pumps filled with saline vehicle or AngII (120 ng/kg per min) were implanted subcutaneously in 8-week-old normotensive rats and infused for 4 weeks in F344 rats (saline, n = 10; AngII, n = 10) and WKY rats (saline, n = 10; AngII, n = 9). Basal BP, HR and the responses to an acoustic startle stimulus (duration 0.7 s, 115 dB) were recorded in conscious rats. The structure of the carotid artery and aorta was determined in 4% formaldehyde-fixed arteries. 3. Compared with WKY rats, vehicle-treated F344 rats had lower bodyweight (BW; 266 +/- 7 vs 299 +/- 9 g; P < 0.05) and heart weight (0.80 +/- 0.02 vs 0.98 +/- 0.04 g; P < 0.05) and higher aortic systolic BP (SBP; 131 +/- 1 vs 123 +/- 5 mmHg; P < 0.001) and diastolic BP (98 +/- 3 vs 89 +/- 2 mmHg; P < 0.001). In F344 rats, compared with the WKY rats, the wall thickness/BW ratio was increased in the carotid artery (156 +/- 9 vs 131 +/- 6 nm/g; P < 0.05) and abdominal aorta (264 +/- 13 vs 217 +/- 12 nm/g; P < 0.05) and decreased in the thoracic aorta (246 +/- 13 vs 275 +/- 8 nm/g; P < 0.05). There was no difference in elastin and collagen density. Angiotensin II differentially enhanced BP in both strains: (SBP: 163 +/- 5 and 132 +/- 4 mmHg in F344 and WKY rats, respectively; P(strain x treatment) < 0.05). Circumferential wall stress was increased in the aorta of F344 rats compared with WKY rats (1176 +/- 39 vs 956 +/- 12 kPa (P < 0.001) and 1107 +/- 42 vs 813 +/- 12 kPa (P < 0.001) in thoracic and abdominal aortas, respectively). The startle response was amplified in F344 rats, with enhanced increases in SBP and pulse pressure (PP) and bradycardia compared with responses of WKY rats (+44 +/- 9 mmHg, +10 +/- 2 mmHg and -40 +/- 17 b.p.m., respectively, in F344 rats vs+28 +/- 4 mmHg, + 4 +/- 2 mmHg and -19 +/- 10 b.p.m. in WKY rats, respectively; P(strain) < 0.05 for BP and PP). The startle response was not affected by AngII. 4. These results indicate a higher BP producing an increase in wall thickness in F344 rats compared with WKY rats. We propose that an increase in sympathetic nervous activity causes these haemodynamic differences, as suggested by the excessive increase in BP during an acoustic startle stimulus. Angiotensin II increased BP in F344 rats, but did not exaggerate the increase in BP during the startle reaction.

Acoustic Stimulation↗

Comparison of various techniques used to estimate spontaneous baroreflex sensitivity (the EuroBaVar study).

This study compared spontaneous baroreflex sensitivity (BRS) estimates obtained from an identical set of data by 11 European centers using different methods and procedures. Noninvasive blood pressure (BP) and ECG recordings were obtained in 21 subjects, including 2 subjects with established baroreflex failure. Twenty-one estimates of BRS were obtained by methods including the two main techniques of BRS estimates, i.e., the spectral analysis (11 procedures) and the sequence method (7 procedures) but also one trigonometric regressive spectral analysis method (TRS), one exogenous model with autoregressive input method (X-AR), and one Z method. With subjects in a supine position, BRS estimates obtained with calculations of alpha-coefficient or gain of the transfer function in both the low-frequency band or high-frequency band, TRS, and sequence methods gave strongly related results. Conversely, weighted gain, X-AR, and Z exhibited lower agreement with all the other techniques. In addition, the use of mean BP instead of systolic BP in the sequence method decreased the relationships with the other estimates. Some procedures were unable to provide results when BRS estimates were expected to be very low in data sets (in patients with established baroreflex failure). The failure to provide BRS values was due to setting of algorithmic parameters too strictly. The discrepancies between procedures show that the choice of parameters and data handling should be considered before BRS estimation. These data are available on the web site (http://www.cbi.polimi.it/glossary/eurobavar.html) to allow the comparison of new techniques with this set of results.

Adult↗

Different vascular responsiveness to angiotensin II in two normotensive rat strains.

Rats of the Fischer 344 (F344) and Wistar Kyoto (WKY) strains are known to present differences in stimuli responses involving the renin-angiotensin system and in cardiovascular responses to an acoustic startle stimulus. Here we compared the vascular reactivity to angiotensin II (ANG II) of these normotensive, inbred rat strains. Blood pressure (BP) and heart rate (HR) were recorded in conscious rats, before and after a neurohumoral blockade obtained by successive administration of chlorisondamine, enalapril, a V1-vasopressinergic receptor antagonist (Manning compound) and atropine methyl nitrate. BP was restored by a constant infusion of noradrenaline. Boluses of ANG II ranging from 0.001 to 1280 ng/kg were injected randomly. Average dose-response curves were established. After neurohumoral blockade, the minimum mean BP (MBP) produced by hydralazine (3 mg/kg, i.v.) and the maximum MBP produced by noradrenaline (60 microg/mL and 800 microL/min, i.v.) were used to reflect arterial wall structure. The maximal systolic blood pressure (SBP) and pulse pressure (PP) responses to ANG II were higher in F344 compared with WKY (+86 +/- 3 mmHg vs. +71 +/- 3 mmHg, P < 0.01 for SBP, +31 +/- 2 mmHg vs. +18 +/- 1 mmHg, P < 0.001 for PP). After the ANG II type 1 (AT1) receptor blocker valsartan, ANG II had no significant effect on BP. F344 and WKY exhibited the same maximum MBP in response to noradrenaline. However, MBP level following hydralazine was higher in F344 (F344: 48 +/- 2 mmHg vs. WKY: 37 +/- 3 mmHg, P < 0.01). The amplification in F344 of the vasoconstrictive response to ANG II mediated by AT1 receptors is compatible with a high number of AT1 receptors in this strain. In F344, the exaggerated systolic and PP responses to ANG II and the higher MBP level after hydralazine most likely reflect a structural modification of the arterial wall such as hypertrophic remodelling in F344.

Angiotensin II↗

Elastin mutation is associated with a reduced gain of the baroreceptor--heart rate reflex in patients with Williams syndrome.

Microdeletion of chromosome 7q, encompassing the elastin locus, has been identified in patients with Williams syndrome (WS). This study tested the hypothesis that loss of medial elastin affects the discharge of baroreceptors and consequently the baroreflex sensitivity (BRS). Eight untreated patients with WS (14.8 +/- 2.4 y, m +/- SEM) were compared to 8 healthy subjects (15.1 +/- 2.3 y). Blood pressure (BP) was recorded using a Finapres monitor in the supine position. Systolic BP (SBP) levels were 117.8 +/- 4.4 mmHg in WS compared to 110.9 +/- 5.7 in controls (ns). Pulse rate (PR, taken as a surrogate for heart rate) was higher in the WS (89.6 +/- 1.0 vs 74.1 +/- 2.3 beats/min in controls, P < 0.01). The variance (total power) of PI variability was reduced in WS subjects. The amplitudes of the low frequency (LF, 0.1 Hz) and high frequency (HF, respiratory) PI component (modulus) were reduced in WS (210.5 +/- 4.3 vs 34.6 +/- 2.6 ms, P = 0.02 for LF, for HF). The gain of the SBP-PI transfer function was diminished in the low frequency (LF, 0.1 Hz) and the HF range as well (5.8 +/- 0.7 vs 12.1 +/- 1.8 ms/mmHg for LF, P < 0.01 and 6.2 +/- 1.0 vs 21.7 +/- 4.6 ms/mmHg for HF, P < 0.01). The BRS obtained with the sequence technique was also reduced in WS (8.2 +/- 0.9 vs 21.5 +/- 2.9 ms/mm Hg in controls, P < 0.001). The percent of beats involved in baroreflex sequences observed in WS was also diminished to 20% compared to 48% in controls (P < 0.001). In conclusion a BRS reduction associated with a PR elevation was observed in normotensive WS subjects. It is likely abnormal elastic fiber assembly at the arterial level alters baroreceptor discharges.

Adolescent↗

Sympathetic and cardiac baroreflex function in panic disorder.

BACKGROUND: Recent reports have demonstrated increased cardiac risk, and an association with essential hypertension in patients with panic disorder. The cause is not known, but possibly involves sympathetic nervous activation. In this study, we evaluated the arterial baroreflex control of vascular sympathetic nervous outflow and cardiac baroreflex function in panic disorder patients. METHODS AND RESULTS: We studied nine patients suffering from panic disorder and ten healthy subjects. Microneurographic recording of muscle sympathetic nerve activity (MSNA) was made with simultaneous recording of blood pressure (BP) and electrocardiogram (ECG). The relationship between MSNA and spontaneous diastolic BP (DBP) changes was assessed at rest and was defined as the arterial baroreflex control of MSNA. Cardiac baroreflex function was assessed using the sequence method. Anxiety was assessed using Spielberger's anxiety state and trait inventory. The slopes of the relationship between MSNA and DBP were more negative (steeper) in the panic disorder group compared with the control subjects (-5.97 +/- 0.45 versus -3.06 +/- 0.43 bursts/100 heart beats per mmHg, P < 0.001). Panic disorder patients had significantly higher state and trait anxiety scores. The slope of the relationship between MSNA and diastolic BP was significantly related to the trait anxiety of the subjects. There was no difference between the cardiac baroreflex sensitivity between the two groups. CONCLUSION: Patients with panic disorder exhibit enhanced reflex gain of the arterial baroreflex control of MSNA but no change in the cardiac baroreflex. While any clinical significance this observation might have in relation to increased cardiac risk in panic disorder, or to concordance with essential hypertension, remains to be elucidated, increased reactivity of vasoconstricting sympathetic nerves may be a trait characteristic in this cohort.

Adult↗