[Variability of the R-R interval and spontaneous baroreflex before and after exposure to weightlessness].
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Baroreflex↗
Biomedical subjects
C Gharib
Publications and source records attributed to C Gharib.
Sympathetic nervous activity and cardiovascular variability after a 3-day tail suspension in rats.
The effects of a 3-day tail suspension on central and peripheral sympathetic activity were studied in rats by determining the in vivo noradrenaline (NA) turnover in the brain cell groups involved in central blood pressure control (A1, A2, A5 and A6) and in two peripheral organs, heart and kidneys. In addition, cardiovascular parameters and their variabilities were investigated by recording blood pressure (BP) and heart rate (HR) before and after suspension. These measurements were processed by spectrum analysis to assess the influence of tail suspension on autonomic balance. The NA turnover in the suspended rats was markedly reduced in A2 (-49%, P < 0.01) and A5 (-38%, P < 0.01) nuclei but unchanged in A1 and A6 cell groups compared with the control rats. Peripheral NA turnover was decreased in cardiac atria (-44%, P < 0.001) and ventricles (-27%, P < 0.01) while it was unchanged in kidneys after suspension. The BP, HR and their variabilities were similar in both groups of animals and showed no changes after suspension compared with baseline values. Spectrum analysis of BP and HR in our conscious suspended rats revealed no changes in power spectrum density or in peak frequencies. The discrepancy between the decrease in central sympathetic activity and the absence of changes in cardiovascular parameters after tail suspension raises the question of the validity of the tail suspended rat model when studying the cardiovascular deconditioning observed in humans after an exposure to actual or simulated weightlessness.
Animals↗
Hormone changes induced by 37.5-h head-down tilt (-6 degrees) in humans.
Endocrine regulation of hormones and electrolytes during 37.5 h of -6 degrees head down tilt (HDT) was studied in 13 men. The acute effects of simulated weightlessness are today well documented, but no study has been made concerning the hormone changes between 12 h and 2 days of HDT. Plasma volume showed a maximal increase of 9.23 (SEM 1.97)% after 6.5 h (P < 0.01) and had returned to prestudy levels after 13.5 h of HDT. From 1.5 h to 4 h of HDT, C-terminus and N-terminus atrial natriuretic peptide (ANP) concentrations in plasma were increased by about 50% (P < 0.01) and thereafter declined to pre-HDT levels. Plasma renin activity (PRA) was decreased by 47% (P < 0.05) after 4 h of HDT; PRA increased after 23.5 h to 60%; noradrenaline concentration decreased immediately and remained low up to 37.5 h. Diuresis and natriuresis were evident during the 1st day of HDT, resulting in a marked increase in the urinary Na+. These results showed that the initial hormone (ANP, PRA) changes during HDT did not last more than 13.5 h and that after 24 h a new state would seem to have been established to adapt the body to hypovolaemia.
Adult↗
Comparison of the effects of spaceflight and hindlimb-suspension on rat pituitary vasopressin and brainstem norepinephrine content.
To compare actual spaceflight to ground-based simulation (hindlimb-suspension), we measured the norepinephrine (NE) content in A1, A2, A5 and A6 (locus coeruleus) and the vasopressin content in the neurohypophysial system. The experimental period was of 9 days' duration. The NE content in the locus coeruleus decreased significantly in rats flown for 9 days (67%, p < 0.001), but showed no significant changes after hindlimb-suspension. These results demonstrated that suspended rats adapted better to weightlessness-simulation than flown rats to actual microgravity. In rats flown aboard SLS-1, the vasopressin content was significantly increased in the posterior pituitary (71%, p < 0.01), and was decreased in the hypothalamus (49%, p < 0.05). In 9-day suspended rats pituitary vasopressin levels were unchanged, while in the hypothalamus a significant decrease was noted (21%, p < 0.05). It was concluded that spaceflight changes in pituitary vasopressin levels and in the locus coeruleus NE content were consistent with a stress reaction, occurring during and/or after landing. These results confirmed that hindlimb-suspension model constitutes a valid and less stressful [correction of lesstressful] ground-based simulation of microgravity in rats.
Animals↗
Altered autonomic regulation of cardiac function during head-up tilt after 28-day head-down bed-rest with counter-measures.
The effects of 28 days continuous 6 degrees head-down tilt bed-rest on heart rate variability and the slope of the spontaneous arterial baroreflex were evaluated during supine rest and the first 10 min of 60 degrees head-up tilt. Twelve healthy men were assigned to either a no counter-measure (No-CM), or a counter-measure (CM) group so that there was no difference in maximal oxygen uptake. Counter-measures consisted of short-term, high resistance exercise for 6 days per week from days 7-28, and lower body negative pressure (-28 mmHg) for 15 min on days 16, 18, 20 and 22-28. In spite of balanced between-group fitness, mean RR-interval was different between the No-CM and the CM group prior to bed-rest, but neither this nor any other variables showed significant counter-measure by bed-rest interaction effects. Therefore, all data presented are from the main effects of bed-rest or tilt from the analysis of variance. RR-interval was reduced significantly by bed-rest and by tilt (P < 0.0001). Indicators from spectral analysis of heart-rate variability suggested reduced parasympathetic nervous system activity with bed-rest (P < 0.01) and head-up tilt (P < 0.05), and increased sympathetic nervous system activity after bed-rest (P < 0.01). An indicator of complexity of cardiovascular control mechanisms, taken from the slope (beta) of log spectral power vs. log frequency relationship, suggested reduced complexity with bed-rest (P < 0.05) and head-up tilt (P < 0.01). The spontaneous baroreflex slope was reduced significantly by bed-rest (P < 0.03) and by head-up tilt (P < 0.04). Taken together, these data support the concept of altered autonomic nervous system function in the aetiology of cardiovascular deconditioning with bed-rest or space travel; and it would appear that no benefit is derived from these specific counter-measures.
Adult↗
Fluid-regulating and sympathoadrenal hormonal responses to peak exercise following cardiac transplantation.
Orthotopic heart transplantation results in cardiac denervation that can disrupt the normal regulation of hydromineral balance. This study compared the exercise-induced variations in plasma osmolality; atrial natriuretic peptide (ANP), arginine vasopressin (AVP), norepinephrine (NE), epinephrine (E), and dopamine (DA) concentrations; and plasma renin activity (PRA) of six cardiac transplant recipients (HTX) and six healthy age-matched controls (C) submitted to graded upright maximal cycling. Venous blood samples were obtained at rest, at submaximal (70% O2 uptake) and peak exercise, and after 10 and 30 min of sitting recovery. Peak O2 uptake was not different between groups despite lower maximal heart rate in HTX (136 +/- 6 vs. 183 +/- 9 beats/min). Baseline plasma ANP and PRA were higher in HTX (203 +/- 55 pg/ml and 29.9 +/- 7.4 ng.ml-1 x h-1) than in C (71 +/- 17 pg/ml and 5.4 +/- 0.96 ng.ml-1 x h-1); AVP was lower in HTX than in C (1.1 +/- 0.3 vs. 3.2 +/- 0.8 pg/ml; P < 0.05); and circulating E, NE, and DA were not different between groups. Exercise resulted in more marked increases in HTX than in C for ANP (300 vs. 100%), AVP (2,000 vs. 300%), NE (860 vs. 500%), and DA (611 vs. 187%) but not for PRA and a higher E response in C than in HTX (455 vs. 1,258%). These observations confirm that the potential for ANP release to central volume loading is independent of intact cardiac innervation. The exaggerated AVP response in HTX could, however, reflect the absence of inhibitory influences consecutive to denervation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal Cortex Hormones↗
Cardiac and plasma atrial natriuretic peptide after 9-day hindlimb suspension in rats.
To determine atrial natriuretic peptide (ANP) adaptation to simulated weightlessness, immunoreactive plasma (ir-NH2- and ir-COOH-terminals) and atrial (ir-COOH-terminal) ANP levels, atrial mRNA expression, immunoreactive cardiocyte ANP levels (ir-NH2- and ir-COOH-terminals), and ultrastructural observations of granules in atrial cardiocytes were assessed in male Wistar rats after a 9-day hindlimb suspension. Plasma ir-NH2- and ir-COOH-terminal ANP concentrations decreased by 17 (P < 0.05) and 37% (P < 0.05), respectively, in suspended rats. A concomitant ir-COOH-terminal ANP content reduction was also observed in left (31%; P < 0.01) and right atria (25%; P < 0.05). Atrial ANP mRNA expression was severely depleted in the right atrium and less so in the left atrium after 9 days of hindlimb suspension. Immunocytochemistry observations demonstrated lowered NH2- and COOH-terminal ANP immunoreactivities in left and right atria from suspended rats. A reduced number of storage granules (dense granules) in both atria was also noted on ultrastructural analysis. It was concluded that ANP biosynthesis, storage, and release were decreased after a 9-day hindlimb suspension.
Animals↗
Adverse effects of strenuous exercise: a densitometric and histomorphometric study in the rat.
To investigate the manner in which cancellous bone in different skeletal sites and within a bone site adapts to strenuous training, 5-wk-old male rats were subjected to intensive treadmill running [80% of maximal O2 consumption (VO2max)] for 11 wk. VO2max, tibia length, and bone mineral density were measured. Histomorphometric analysis was performed in the epiphysis, primary spongiosa (1 zero sp) and secondary spongiosa (2 zero sp) of the contralateral proximal tibia, and the 2 zero sp of thoracic and lumbar vertebrae. VO2max was increased by 39%. No changes were observed in vertebrae. Tibia length, 1 zero sp bone volume, and number of trabeculae were significantly decreased, indicating a retarded longitudinal bone growth. Bone mineral density in the proximal tibia was significantly decreased. In the epiphysis, a trabecular thinning and an increase of trabecular number were shown. In the 2 zero sp, bone volume and number of trabeculae were significantly decreased. The increased total eroded surfaces could indicate an early but transient increase in bone resorption activity. Osteoid thickness was reduced, whereas osteoclast number and osteoid surfaces were unchanged, suggesting that the observed bone loss was mostly due to an impaired osteoblastic activity. In conclusion, 1) strenuous training in young rats reduces longitudinal bone growth and induces bone loss, 2) the cancellous bone adaptation is site specific, and 3) the bone loss is mainly due to decreased osteoblastic activity rather than a global adaptation of bone remodeling.
Animals↗
Reduced spontaneous baroreflex response slope during lower body negative pressure after 28 days of head-down bed rest.
Effects of 28 days of continuous 6 degrees head-down tilt bed rest on spontaneous vagally mediated baroreflex response slope were evaluated from beat-by-beat relationships between R-R interval and systolic arterial blood pressure. Twelve healthy men (age 27-42 yr) were assigned to either countermeasure (CM) or no-countermeasure (no-CM) groups. CM consisted of strenuous short-term exercise once per day 6 days/wk from days 7 to 28 and lower body negative pressure (LBNP) for 15 min on days 16, 18, 20, and 22-28. Spontaneous baroreflex slope was evaluated by application of linear regression to sequences of at least three beats in which systolic blood pressure and R-R interval changed in the same direction. Measurements were made pre-, mid- (day 15), and post-bed rest at rest and during progressive LBNP tests (3 min at each of -20, -30, -40, and -50 mmHg). R-R interval decreased progressively and significantly (P < 0.0001) over duration of bed rest. Spontaneous baroreflex slope at rest in pre-bed rest was 18.5 +/- 2.1 ms/mm Hg for CM and 14.9 +/- 1.6 ms/mmHg for no-CM. There was a significant reduction in baroreflex slope as a function of bed rest, and it was further reduced during LBNP (P < 0.0001). Between CM and no-CM groups differences existed, but these were present pre-bed rest and appeared unaffected by countermeasures.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effect of 28-day head-down bed rest with countermeasures on heart rate variability during LBNP.
The effect of exercise and LBNP countermeasures on the cardiovascular deconditioning response have been evaluated by the study of heart rate variability during progressive LBNP tests before, during (day 15), and after 28 d continuous 6 degrees head-down tilt bed rest. Twelve healthy men (age 27-42 years) were studied in two groups. Six were assigned to a countermeasure regime (CM) consisting of strenuous short-term resistance exercise once per day, 6 days per week from day 7 to day 28, combined with lower body negative pressure (LBNP, -28 mm Hg) for 15 min on days 16, 18, 20, and 22-28. Results were compared with data from six subjects, matched on the basis of maximum oxygen uptake, who received no countermeasures (No-CM). The main effects of bed rest were seen in reductions in RR-interval, and in total spectral power. The results of spectral analysis showed a significant reduction in an index of parasympathetic activity with a nonsignificant increase in a sympathetic indicator. The fractal component of heart rate variability was reduced also, suggesting a change in cardiovascular control mechanisms. Although there were significant differences between CM and No-CM for a number of variables, there were no bed rest by countermeasure interaction effects in the statistical analysis. These results suggested that this particular series of countermeasures was ineffective in preventing at least certain changes indicative of cardiovascular deconditioning with 28 d head-down tilt bed rest.
Adult↗
ANP binding sites are increased in choroid plexus of SLS-1 rats after 9 days of spaceflight.
Specific alpha-rat 28-amino acid atrial natriuretic peptide [ANP(99-126)] (rANP) binding sites in choroid plexus and meningia of rats flown for 9 days on the mission STS-40 (SLS-1) carried on the space shuttle Columbia in June 1991 were analyzed after incubation of brain sections with 125I-rANP and autoradiography, using computer-assisted microdensitometric image analysis. The number of 125I-rANP binding sites (expressed by Bmax values) in the choroid plexus of lateral and third ventricles of these rats was significantly increased (x 1.5-2.5 times), as compared with that found in ground control rats. No differences in the binding affinity (deducible from Kd values) were observed at the level of these structures. The choroid plexus from the fourth ventricle of the same rats displayed no changes in the binding capacity or affinity after the spaceflight. Meningia from the rats flown in space did not demonstrate any significant modifications of the number of 125I-rANP binding sites, but displayed a significant increase in Kd values, which suggested a reduced affinity of the meningeal ANP receptors during a 9-d spaceflight. The possibility that atrial natriuretic peptide may be involved in the regulation of fluid and electrolyte fluxes in the brain, during adaptation to microgravity, through modified expression of specific high affinity receptors, mainly in choroid plexus from forebrain or in meningia, must be considered.
Animals↗
Effects of a short term hindlimb suspension on central and peripheral norepinephrine turnover in rats.
The loss of appropriate cardiovascular reflexes which contributes to the cardiovascular deconditioning observed after an exposure to actual or simulated microgravity (in man or animals) is well known, but the mechanisms responsible remain unclear. This protocol, a 2.5 h hindlimb suspension in rats, was undertaken to study the early adaptation of the sympathetic neurons involved in arterial pressure regulation: we determined central norepinephrine (NE) turnover in the brainstem catecholaminergic cell groups responsible for the central cardiovascular regulation i.e. A1, A2 (rostral and caudal), A5 and A6 cell groups and peripheral NE turnover in target organs (heart and kidneys). The NE turnover in suspended rats significantly decreased in rostral A2 (48% p < 0.001), caudal A2 (52% p < 0.001) and A5 (40% p < 0.05) cell groups while it was unchanged in A1 and A6 cell groups compared with rats attached to the suspension device but maintained in the horizontal position. The short term hindlimb suspension did not alter the NE turnover in cardiac atria and ventricles or in kidneys nor did it alter the blood variables studied (hematocrit, osmolality, plasma sodium, potassium, proteins and renin concentration). We concluded that a 2.5 h hindlimb suspension reduced noradrenergic neuron activity in A2 and A5 cell groups involved in the central control of arterial pressure and particularly in the baroreceptor reflex mechanisms. This duration was probably not sufficient to modify the NE turnover in the two peripheral organs studied.
Animals↗
Evaluation of spontaneous baroreflex response after 28 days head down tilt bedrest.
The spontaneous baroreflex response was evaluated during supine rest and head up tilt (60 degrees) before and immediately after a 28 day 6 degrees HDT bedrest in 6 healthy adult men (age 30-42 years). Sequences of 3 or more beats where RR-interval and systolic blood pressure changed in the same direction were used to evaluate baroreflex response slope (BRS). Prior to bedrest, the mean BRS and RR-interval were 18.0 +/- 3.9 ms/mm Hg and 926 +/- 61 ms at rest and 10.5 +/- 2.5 ms/mm Hg and 772 +/- 63 ms during the first 10 min of 60 degrees tilt. Following bedrest, these values changed to 15.6 +/- 2.7 ms/mm Hg and 780 +/- 53 ms at rest, and to 6.5 +/- 1.2 ms/mm Hg and 636 +/- 44 ms during tilt. Thus, (1) the spontaneous baroreflex can be evaluated in human subjects during experiments of orthostatic stress; (2) the baroreflex slope was reduced on going from supine to the head up tilt position; and (3) 28 days of bedrest reduced the spontaneous baroreflex slope.
Adult↗
Atrial natriuretic factor: plasma concentration and specific binding to renal glomeruli during the development of genetic hypertension in rats of the Lyon strain.
1. The pathophysiologic role of atrial natriuretic factor (ANF) in genetic hypertension was investigated in 5- and 21-week-old genetically hypertensive (LH), normotensive (LN) and low blood pressure (LL) rats of the Lyon strain. 2. Plasma ANF was significantly higher in 5-week-old LH than in age-matched LN and LL animals. It tended to be lower in 21-week-old LH than in LN rats. 3. Left and right atrial ANF content was also significantly lower at 21 weeks in the LH group. 4. Glomerular ANF receptors showed a significant decrease in LH in comparison to LL and LN animals.
Animals↗
Immunoreactive arginine vasopressin in the testis: immunocytochemical localization and testicular content in normal and in experimental cryptorchid mouse.
The presence of arginine vasopressin (AVP)-like peptide(s) and AVP receptors has been previously demonstrated in the testis of several species. In this study we examined the immunocytochemical localization of AVP and of its associated neurophysin (NPII) within the mouse testis, and the testicular immunoreactive (IR)-AVP content in normal pubertal and adult mice and in unilaterally cryptorchid animals. Immunostaining was conducted on fresh frozen adult testicular sections and on cultured testicular cells using the avidin-biotin immunoperoxidase technique. Immunoreactivities for AVP and NPII were localized at the periphery of the seminiferous tubules. Staining for AVP and NPII was reduced in testes showing impaired spermatogenesis. AVP and NPII immunoreactivities were present in cultured Sertoli cells, but staining was undetectable in cultured Leydig cells. Negative controls were obtained by applying antiserum that had been preabsorbed with excess peptides in place of primary antiserum. Mouse testes were found to contain IR-AVP, which co-eluted with synthetic AVP on HPLC and diluted in parallel in a specific RIA for AVP. Levels of IR-AVP expressed as pg/mg wet-weight testis were significantly higher (p < 0.05) in pubertal (36.6 +/- 1.5) than in adult animals (27.4 +/- 1.5). Experimental unilateral cryptorchidism in adult animals resulted 2 wk later in a marked reduction (p < 0.01) in IR-AVP levels in the abdominal testis (18.1 +/- 1.0 pg/mg testis) as compared to the contralateral scrotal testis (29.8 +/- 1.1 pg/mg testis).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Local regulation of testicular immunoreactive-arginine vasopressin and steroidogenesis by naloxone.
The effects of intratesticular injection of naloxone, a universal opioid antagonist, on testicular immunoreactive (IR)-arginine vasopressin (AVP) content and on in vitro testosterone production by Leydig cells were investigated in the mouse. Bilateral intratesticular injection of increasing doses of naloxone (0.1-10 micrograms/testis) resulted 24 h later in a dose-dependent increase in testosterone production by Leydig cells incubated for 3 h in the presence or absence of hCG (100 ng/ml). Unilateral intratesticular injection of naloxone (10 micrograms) similarly enhanced basal and hCG-stimulated testosterone production by Leydig cells, but production was not modified in Leydig cells from the contralateral vehicle-injected testis, nor was it changed when the same dose was injected subcutaneously. Unilateral intratesticular injection of 10 micrograms naloxone led to a dose-dependent increase in the hCG-responsiveness without altering the slope of the hCG dose-response curve. In vitro exposure of Leydig cells to increasing doses of naloxone (10(-9) to 10(-7) M) did not alter either basal or hCG-stimulated testosterone production. Testicular IR-AVP content declined in a dose-dependent manner in naloxone-injected testis, but remained unchanged in the contralateral vehicle-injected testis and in testis from animals that received similar doses of naloxone subcutaneously. Since AVP has been shown to locally exert a negative control on testosterone production within the testis, it might be hypothesized that the increased Leydig cell activity after local naloxone administration results from reduced intratesticular IR-AVP levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Spontaneous baroreflex by sequence and power spectral methods in humans.
Beat-by-beat variations in blood pressure and RR-interval are interrelated by the actions of baroreflex and non-baroreflex responses. This study had two purposes: (1) to examine the spontaneous relationships between RR-interval and systolic blood pressure to determine the relative occurrence of baroreflex and non-baroreflex responses in humans, and (2) to compare the beat-sequence method with a cross spectral estimate of the baroreflex response slope. Eight healthy men were studied during 10 h of quiet, seated rest, and six men and three women were studied during rest, rest plus fixed pace breathing, and a cold pressor test. RR-interval and continuous, non-invasive arterial blood pressure were measured with a computerized system. A baroreflex sequence was defined by a series of at least three consecutive heart beats in which systolic pressure and the following RR-interval either both increased or both decreased. A non-baroreflex relationship was defined by sequences of at least three beats by opposite directional changes of RR-interval and systolic pressure of that beat. The results showed that there were approximately 30% as many non-baroreflex compared to baroreflex slopes. Individual subject mean baroreflex and non-baroreflex slopes were highly correlated (r = 0.72, P < 0.001). Absolute slope values were not different, and they were unaffected by time, fixed pace breathing, or cold pressor test. The data showed the relatively simple beat-by-beat sequence method to yield spontaneous baroreflex response slopes that were quantitatively similar to, and highly correlated with (r = 0.85-0.94), baroreflex response slopes calculated by spectral analysis methods.
Adult↗
Increased plasma levels of atrial natriuretic factor, renin activity, and leukotriene C4 in chronic obstructive pulmonary disease.
We studied atrial natriuretic factor (ANF), plasma renin activity (PRA), and plasma levels of leukotrienes (LTs) B4 and C4 in 23 patients with COPD undergoing right cardiac catheterization for suspected pulmonary hypertension. Hemodynamic measurements together with concomitant ANF levels (both in venous and pulmonary artery blood and right atrial and pulmonary artery plasma levels of LTC4 and LTB4, were determined at rest (T0), after 30 min of breathing oxygen (3 L/min) (T1), and after 30 min recovering and breathing air (T2). Patients with effective exacerbation or definitive evidence of left ventricular disease, hypertension, arrhythmias, or vasodilator or diuretic therapy were excluded. Increased levels of ANF, both in peripheral venous blood (117 +/- 65 pg/ml) and the pulmonary artery (153 +/- 75 pg/ml), were found in patients with COPD, with or without pulmonary hypertension. Levels of LTC4 were also significantly increased (366 +/- 406 pg/ml) when compared with our control values. No correlations among ANF, LTC4 values, functional tests, and hemodynamic measurements were found. Brief increased levels of oxygen did not modify ANF or LTC4 plasma levels, either in patients with or without pulmonary hypertension.
Atrial Natriuretic Factor↗