Biomedical subjects

T Mano

Publications and source records attributed to T Mano.

At least 37 records · Page 2Linked to original sources

PubMed2001

A comparative cytogenetic study of chromosome homology between chicken and Japanese quail.

In order to construct a chicken (Gallus gallus) cytogenetic map, we isolated 134 genomic DNA clones as new cytogenetic markers from a chicken cosmid DNA library, and mapped these clones to chicken chromosomes by fluorescence in situ hybridization. Forty-five and 89 out of 134 clones were localized to macrochromosomes and microchromosomes, respectively. The 45 clones, which localized to chicken macrochromosomes (Chromosomes 1-8 and the Z chromosome) were used for comparative mapping of Japanese quail (Coturnix japonica). The chromosome locations of the DNA clones and their gene orders in Japanese quail were quite similar to those of chicken, while Japanese quail differed from chicken in chromosomes 1, 2, 4 and 8. We specified the breakpoints of pericentric inversions in chromosomes 1 and 2 by adding mapping data of 13 functional genes using chicken cDNA clones. The presence of a pericentric inversion was also confirmed in chromosome 8. We speculate that more than two rearrangements are contained in the centromeric region of chromosome 4. All 30 clones that mapped to chicken microchromosomes also localized to Japanese quail microchromosomes, suggesting that chromosome homology is highly conserved between chicken and Japanese quail and that few chromosome rearrangements occurred in the evolution of the two species.

Animals↗

PubMed2000

Skin sympathetic neuroeffector response is attenuated dose-dependently by systemic prostaglandin E1 injection in humans.

To clarify the effects of prostaglandin E1 (PGE1) on the vasoconstrictive responses, we compared the correlation between the amplitude of integrated skin sympathetic nerve activity (SSNA) and per cent reduction in skin blood flow (SBF) before and after the infusion of lipo PGE1 and placebo (bolus one-shot infusion, single blind study), and constant rate infusion of PGE1 (10 and 50 ng kg(-1) min(-1) by infusion pump, dose-dependency study) in ten healthy men. SSNA was recorded microneurographically from the median nerve simultaneously with SBF by laser Doppler flowmetry at the index fingertip. The measurement was conducted 30 min after injection of lipo PGE1 or placebo, and during the drip infusion of 10 and 50 ng kg(-1) min(-1) of PGE1 with maneuvers to enhance SSNA. The resting and activated skin blood flow were not significantly different between 10 ng lipo PGE1 and placebo administration, and between baseline and 10, 50 ng kg(-1) min(-1) of PGE1 injection. The vascular response, defined as the slope of regression line between logarithm of amplitude of integrated SSNA bursts and the reduction in SBF, was significantly suppressed by injection of lipo PGE1 as compared with that by placebo. It was also decreased dose-dependently by the constant rate infusion of PGE1 (10 and 50 ng kg(-1) min(-1)). We concluded that the intravenous injection of PGE1 attenuates vasoconstrictive responses to SSNA, and analysis of the relations between SSNA and vasoconstrictive response, i.e. the neuroeffector response, is suggested to be an important tool to assess the drug effect.

Action Potentials↗

PubMed2000

Cyclin A downregulation and p21(cip1) upregulation correlate with GATA-6-induced growth arrest in glomerular mesangial cells.

The GATA-6 transcription factor is reported to be expressed in vascular myocytes. Because glomerular mesangial cells (GMCs) and vascular myocytes have similar properties, we examined whether GATA-6 was expressed in cultured GMCs and whether overexpression of GATA-6 induced cell cycle arrest in GMCs, using a recombinant adenovirus that expresses GATA-6 (Ad GATA-6). GATA-6 expression in GMCs was downregulated when quiescent GMCs were stimulated by serum to reenter the cell cycle. [(3)H]thymidine uptake was inhibited in GMCs infected with Ad GATA-6 in a dose- and time-dependent manner. The expression of cyclin A protein was decreased and that of the cyclin-dependent kinase inhibitor p21(cip1) was increased in GMCs infected with Ad GATA-6. Although the expression of p21(cip1) transcripts did not change remarkably, p21(cip1) protein was stabilized in GMCs infected with Ad GATA-6, suggesting a post-transcriptional regulation of p21(cip1) expression. Northern blot analysis showed that expression of the cyclin A transcript was decreased in Ad GATA-6-infected cells, whereas this decrease of cyclin A was not observed in GMCs derived from p21(cip1) null mice. Our results demonstrate that GATA-6 is endogenously expressed in GMCs and that overexpression of GATA-6 can induce cell cycle arrest. Our results also show that GATA-6-induced cell cycle arrest is associated with inhibition of cyclin A expression and p21(cip1) upregulation. Finally, our results indicate that the GATA-6-induced suppression of cyclin A expression depends on the presence of p21(cip1).

Adenoviridae↗

PubMed2000

Expression of wild-type and noncleavable Fas ligand by tetracycline-regulated adenoviral vectors to limit intimal hyperplasia in vascular lesions.

Proliferation of vascular smooth muscle cells (VSMCs) and the infiltration of T cells and macrophages into vessel wall are considered to be important for intimal lesion formation after balloon angioplasty. Previous studies have shown that Fas ligand (FasL) gene transfer to balloon-injured vessels inhibits lesion formation by killing both proliferating VSMCs and infiltrating inflammatory cells. Here, we describe the construction and utility of a binary, tetracycline-regulated adenovirus system that provides controlled transgene expression in vitro and in vivo. In this system, optimal transgene expression required cotransfection with an adenovirus encoding the tetracycline-dependent trans-activator (rtTA) and induction with doxycycline hydrochloride (DOX), an analog of tetracycline. Using this system, adenovirus constructs were designed that allow regulated expression of wild-type FasL and a noncleavable mutant of FasL (FasL-NC). Transduction of FasL and FasL-NC induced similar extents of apoptosis in proliferating VSMCs in vitro in a manner that was dependent on the doses of the rtTA adenovirus and the presence of DOX in the medium. Furthermore, inhibition of intimal hyperplasia in injured carotid arteries by FasL or FasL-NC transduction was also dependent on cotransfection with the rtTA adenovirus and administration of DOX by subcutaneous injection. In contrast to wild-type FasL, transduction of FasL-NC did not result in the production of soluble (cleaved) FasL in the medium of infected cells in vitro, or in the serum of rats after local gene transfer to carotid arteries. In conclusion, this binary tetracycline-inducible adenovirus system may allow for safer delivery of cytotoxic genes for therapeutic purposes.

Adenoviridae↗

PubMed2000

A comparison of autonomic responses in humans induced by two simulation models of weightlessness: lower body positive pressure and 6 degrees head-down tilt.

Six-degree head-down tilt (HDT) is well accepted as an effective weightlessness model in humans. However, some researchers utilized lower body positive pressure (LBPP) to simulate the cardiovascular and renal effects of a decreased gravitational stress. In order to determine whether LBPP was a suitable model for simulated weightlessness, we compared the differences between these two methods. Ten healthy males, aged 21-41 years, were subjected to graded LBPP at 10, 20 and 30 mmHg, as well as 6 degrees HDT. Muscle sympathetic nerve activity (MSNA) was microneurographically recorded from the tibial nerve along with cardiovascular variables. We found that MSNA decreased by 27% to a similar extent both at low levels of LBPP (10 and 20 mmHg) and HDT. However, at a high level of LBPP (30 mmHg), MSNA tended to increase. Mean arterial pressure was elevated significantly by 11% (10 mmHg) at 30 mmHg LBPP, but remained unchanged at low levels of LBPP and HDT. Heart rate did not change during the entire LBPP and HDT procedures. Total peripheral resistance markedly increased by 36% at 30 mmHg LBPP, but decreased by 9% at HDT. Both stroke volume and cardiac output tended to decrease at 30 mmHg LBPP, but increased at HDT. These results suggest that although both LBPP and HDT induce fluid shifts from the lower body toward the thoracic compartment, autonomic responses are different, especially at LBPP greater than 20 mmHg. We note that high levels of LBPP (>20 mmHg) activate not only cardiopulmonary and arterial baroreflexes, but also intramuscular mechanoreflexes, while 6 degrees HDT only activates cardiopulmonary baroreflexes. We conclude that LBPP is not a suitable model for simulated weightlessness in humans.

Adult↗

PubMed2000

Effects of three days of dry immersion on muscle sympathetic nerve activity and arterial blood pressure in humans.

The present study was performed to determine how sympathetic function is altered by simulated microgravity, dry immersion for 3 days, and to elucidate the mechanism of post-spaceflight orthostatic intolerance in humans. Six healthy men aged 21-36 years old participated in the study. Before and after the dry immersion, subjects performed head-up tilt (HUT) test to 30 degrees and 60 degrees (5 min each) with recordings of muscle sympathetic nerve activity (MSNA, by microneurography), electrocardiogram, and arterial blood pressure (Finapres). Resting MSNA was increased after dry immersion from 23.7+/-3.2 to 40.9+/-3.0 bursts/min (p<0.005) without significant changes in resting heart rate (HR). MSNA responsiveness to orthostasis showed no significant difference but HR response was significantly augmented after dry immersion (p<0. 005). A significant diastolic blood pressure fall at 5th min of 60 degrees HUT was observed in five orthostatic tolerant subjects despite enough MSNA discharge after dry immersion. A subject suffered from presyncope at 2 min after 60 degrees HUT. He showed gradual blood pressure fall 10 s after 60 degrees HUT with initially well-maintained MSNA response and then with a gradually attenuated MSNA, followed by a sudden MSNA withdrawal and abrupt blood pressure drop. In conclusion, dry immersion increased MSNA without changing MSNA response to orthostasis, and resting HR, while increasing the HR response to orthostasis. Analyses of MSNA and blood pressure changes in orthostatic tolerant subjects and a subject with presyncope suggested that not only insufficient vasoconstriction to sympathetic stimuli, but also a central mechanism to induce a sympathetic withdrawal might play a role in the development of orthostatic intolerance after microgravity exposure.

Adult↗

PubMed2000

Increased vasomotor sympathetic nerve activity and decreased plasma nitric oxide release after head-down bed rest in humans: disappearance of correlation between vasoconstrictor and vasodilator.

We hypothesized that the relationship between resting levels of sympathetic vasoconstrictor nerve traffic and dilator substance nitric oxide (NO) release is altered after exposure to microgravity, resulting in abnormal peripheral resistance. To examine the hypothesis, we assessed muscle sympathetic nerve activity (MSNA) (microneurography), an indicator of NO release (plasma nitrite/nitrate concentrations) and leg vascular resistance (venous occlusion plethysmography) in 20 healthy male volunteers before and after 14 days of 6 degrees head-down bed rest (HDBR), the ground-based analogue of microgravity. MSNA increased, while plasma nitrite/nitrate concentrations decreased after HDBR. A significant positive correlation observed between MSNA and plasma nitrite/nitrate concentrations before HDBR disappeared after HDBR. Leg vascular resistance increased after HDBR. In conclusion, an imbalance between sympathetic vasoconstrictor traffic and NO release might contribute to elevated peripheral vascular resistance following HDBR.

Adult↗

PubMed2000

Muscle sympathetic nerve activity during handgrip and post-handgrip muscle ischemia after exposure to simulated microgravity in humans.

To examine the effect of 6 degrees head-down bed rest (HDBR) on vasomotor sympathetic responses to isometric forearm exercise, 16 healthy male subjects aged 20-36 years performed voluntary isometric handgrip (HG) at 30% of maximal voluntary contraction until fatigue, followed by 2 min of post-handgrip muscle ischemia (PHGMI) with 250 mmHg of cuff inflation, before and after 14 days of HDBR. Time to fatigue and maximal voluntary HG force were not affected by HDBR. Pre-exercise baseline muscle sympathetic nerve activity (MSNA, measured by microneurography), heart rate (measured by electrocardiogram) and mean blood pressure (measured by Portapres) increased after HDBR. Increases in MSNA were similar during HG but significantly lower during PHGMI (P < 0.01) after HDBR. Responses of heart rate and mean blood pressure during HG and PHGMI were not affected by HDBR. These results suggest that the magnitude of muscle metaboreflex during isometric forearm exercise might be attenuated after 14 days of simulated microgravity.

Adult↗

PubMed2000

Argatroban inhibits intraocular fibrin formation after vitrectomy in rabbits.

OBJECTIVES: To examine whether the specific thrombin inhibitor argatroban can prevent anterior chamber, pupillary area, and anterior vitreous fibrin formation after vitrectomy and lensectomy in rabbits. METHODS: Argatroban was infused into the vitreous cavities of Japanese albino rabbits for 5 minutes after pars plana vitrectomy and lensectomy. Slitlamp microscopy and indirect ophthalmoscopy were performed at postoperative hours 0.5, 1, 2, 3, and 6, and at postoperative days 1, 2, 3, and 7, and the amounts of fibrin formation in the anterior chamber, pupillary area, and anterior vitreous were scored from grade 0 to 4. RESULTS: Argatroban prevented fibrin formation from 0.5 hours postoperatively in a dose-dependent manner. In the eyes treated with 0.01% argatroban, the median score for postoperative fibrin formation was significantly less than that in control eyes between hours 1 and 3 (hour 1, P =.02; hour 2, P =.005; and hour 3, P =.003); the eyes treated with 0.003% argatroban also had significantly less fibrin than control eyes between 1 and 2 hours (hour 1, P =.005; hour 2, P =.03). CONCLUSION: These results indicate that argatroban inhibits intraocular fibrin formation in an experimental rabbit model. CLINICAL RELEVANCE: Argatroban may be useful clinically in cases that often produce fibrin postoperatively, such as proliferative vitreoretinopathy and proliferative diabetic retinopathy.

Animals↗

PubMed2000

Substance P-induced cadherin expression and its signal transduction in a cloned human corneal epithelial cell line.

Although the absence of Substance P (SP), a neurotransmitter in the trigeminal nerve, has been speculated as a cause for developing neurotrophic keratitis, its exact pathogenesis is still not clarified. In a previous report, we showed with electron microscopic examination that epithelial cell attachment was weakened in denervated corneas. In this study, SV40-transformed human corneal epithelial cells (HCE-Ts) were used to explore the molecular mechanisms responsible for mediating regulation of E-cadherin expression in response to Substance P receptor stimulation. Expression of the mRNAs for specific SP receptors, neurokinin (NK)-1R, NK-2R, and NK-3R, was demonstrated with RT-PCR. The cells were treated with various concentrations of SP in vitro, and the expression of an adhesion molecule E-cadherin was analyzed by immunofluorescence, immunoblotting, and enzyme-linked immunosorbent assay (ELISA) using an anti-E-cadherin antibody. E-cadherin expression was increased by SP in a dose-dependent manner both in the cytosolic fraction and in the cell membrane fraction. This increase in E-cadherin expression was completely inhibited by Calphostin C (PKC inhibitor) and KN-62 (CaMK inhibitor), but not by H-89 (PKA inhibitor), indicating that SP-induced E-cadherin expression involves the activation of protein kinase C (PKC) and calmodulin kinase (CaMK). SP did not affect cell proliferation at all. All these findings indicate that SP induced E-cadherin expression through PKC and CaMK activation and suggest that a lack of SP may account in part for the pathogenesis of neurotrophic keratitis.

Cadherins↗

PubMed2000

Local neurohumoral regulation in the transition to isolated diastolic heart failure in hypertensive heart disease: absence of AT1 receptor downregulation and 'overdrive' of the endothelin system.

OBJECTIVE: Although isolated diastolic heart failure with preserved left ventricular (LV) systolic function frequently occurs, regulation of local neurohumoral factors in the transition from diastolic dysfunction without signs of heart failure to diastolic failure, a target for therapeutic strategy, remains to be clarified, partly because of a lack of animal models. Our laboratory recently demonstrated that Dahl-Iwai salt-sensitive (Dahl-S) rats fed on a high-salt diet since 7 weeks of age develop hypertension followed by compensated LV hypertrophy at 13 weeks and transition to isolated diastolic heart failure at 19 weeks. METHODS: Gene expression of the components of the renin-angiotensin system, endothelin (ET) system and natriuretic peptide system in the left ventricle was investigated in the transition to isolated diastolic heart failure in this model. RESULTS: The compensated ventricular hypertrophy was associated with slight increases in angiotensin-converting enzyme (ACE) and angiotensin II type-1a (AT1a) receptor mRNA levels. Although preproET-1 (ppET-1) and ET-converting enzyme-1 (ECE-1) mRNA levels were not increased, mRNA levels of ET type-A (ETA) and ET type-B (ETB) receptors were increased. Atrial natriuretic peptide (ANP) mRNA level increased, but not brain natriuretic peptide (BNP) mRNA level. At the decompensated failing stage (at 19 weeks), ACE mRNA level further increased without downregulation of ATla receptor mRNA level. The mRNA levels of ppET-1 and ECE-1 increased with persistent upregulation of mRNA levels of ETA and ETB receptors, and immunohistochemical staining for ET-1 was found at endothelial cells and myocytes. BNP mRNA level increased with a further increase in ANP mRNA level. CONCLUSIONS: The transition to isolated diastolic heart failure in hypertrophied hearts was associated with preserved gene expression of the renin-angiotensin system and 'overdrive' of gene expression of the ET system. BNP gene expression is likely to be activated by the progression of diastolic failure rather than by LV hypertrophy alone.

Analysis of Variance↗

PubMed2000

Roles of renin-angiotensin and endothelin systems in development of diastolic heart failure in hypertensive hearts.

OBJECTIVE: Although interest in diastolic heart failure is growing because of its clinical frequency, little is known about this type of heart failure. Our laboratory recently developed a diastolic heart failure model using Dahl salt-sensitive rat. In this model, gene expression of angiotensin-converting enzyme and endothelin (ET) system in the left ventricle was enhanced at heart failure stage without downregulation of angiotensin type 1a receptor mRNA level. However, the roles of these humoral systems in the transition to diastolic failure remain unclear. METHODS: Subdepressor doses of angiotensin II type 1 (AT1) receptor and ET type A (ETA) receptor antagonists were administered in this model just after onset of hypertension, and their effects were investigated. RESULTS: Neither AT1 nor ETA receptor blockade inhibited the early (13 weeks) compensatory left ventricular (LV) hypertrophy. This form of compensatory hypertrophy is associated with subnormal LV end-systolic stress, which was normalized by AT1 receptor blockade but not by ETA receptor blockade. Progression of LV hypertrophy and fibrosis and transition to heart failure (19 weeks) in the untreated rats were prevented by both antagonists, resulting in normalization of LV end-diastolic pressure and lung weight. AT1 receptor blockade, but not ETA receptor blockade, normalized time constant of LV relaxation. Enhanced gene expression for ET system in the left ventricle observed in the untreated rats was suppressed with AT1 receptor antagonist administration. ETA receptor blockade slightly but significantly elevated the AT1a receptor mRNA level as compared with the untreated rats. CONCLUSIONS: RAS and ET system contribute to the transition to diastolic heart failure through the development of excessive hypertrophy and ventricular fibrosis in hypertensive heart diseases, however, neither RAS nor ET system is mandatory for normal compensation for pressure overload. RAS apparently causes such diastolic effects at least partly through the ET system.

Angiotensin Receptor Antagonists↗

PubMed2000

Scavenging effect of nicorandil on free radicals and lipid peroxide in streptozotocin-induced diabetic rats.

Free radicals and lipid peroxide (LPO), easily formed in the diabetic state, play an important role in the development of diabetic complications. Potentially, nicorandil may reduce the production of free radicals and LPO in various organs. In fact, increased LPO levels in the serum, kidney, and cardiac muscle of diabetic (DM) rats were reduced by nicorandil treatment (N treatment). Xanthine oxidase (XOD), which produces free radicals, was decreased in the liver and increased in the kidney of DM rats compared with control rats, and these changes were prevented by N treatment. The concentration of Cu, Zn-superoxide dismutase (SOD) decreased in the cardiac muscle and increased in the kidney of DM rats, and these changes returned to normal after N treatment. The decreased concentration of Mn-SOD in the liver, kidney, and cardiac muscle from DM rats was also reversed by N treatment. The changes in catalase and glutathione peroxidase (GSH-PX) activities in DM rats were not improved effectively by N treatment. Another K-adenosine triphosphate (K-ATP) channel opener, tilisolol hydrochloride, had an effect similar to that of nicorandil. The effects of nicorandil and tilisolol were studied only in DM rats. These data imply that N treatment, as an antioxidative therapy, may be beneficial in preventing diabetic complications due to lipoperoxidation and free radicals in DM rats.

Animals↗

PubMed2000

Effects of aging on cardiovascular responses to gravity-related fluid shift in humans.

BACKGROUND: Fluid shift induced by postural change causes autonomic neural responses of the cardiovascular system that buffer blood pressure fluctuation. The aim of the study was to clarify the effects of aging on cardiovascular autonomic functions in response to gravity-related fluid shift that unloads or loads the baroreceptors in human subjects. METHODS: A chest electrocardiogram, blood pressure by Finapres, and stroke volume by impedance method were measured in healthy young men (23-31 years old) and healthy elderly men (74-80 years old) during supine rest, at 90 degrees head-up tilt and thermoneutral head-out water immersion. Spectral analysis was applied to the time series data of the R-R intervals (heart rate variability [HRV]) and systolic blood pressure (blood pressure variability [BPV]). The arterial baroreflex gain for heart rate was estimated using frequency transfer function analysis. RESULTS: The young subjects had stable blood pressure, despite the larger amount of fluid shift induced by both tilt and immersion, and had marked changes in HRV and BPV. The elderly subjects failed to maintain stable blood pressure during these perturbations, despite less fluid shift and no significant changes in HRV and BPV. The arterial baroreflex gain for heart rate was not changed in the elderly subjects, whereas the gain decreased with upright in the young subjects and showed an increasing tendency during immersion compared with upright posture. CONCLUSIONS: These findings suggest that the adaptivity of the autonomic nervous system to gravity-related fluid shift is reduced in elderly people, and this may cause blood pressure instability.

Adult↗

PubMed2000

Development of different phenotypes of hypertensive heart failure: systolic versus diastolic failure in Dahl salt-sensitive rats.

OBJECTIVE: There are two phenotypes of heart failure, systolic failure and isolated diastolic heart failure with preserved left ventricular systolic function. Although isolated diastolic heart failure frequently occurs, there are only models for diastolic dysfunction unassociated with heart failure and models with overt diastolic heart failure have not been established. We attempted to develop two different models, i.e. diastolic and systolic failure models, based on hypertension. MATERIALS AND METHODS: Dahl salt-sensitive rats were placed on 8% NaCl diet from 7 weeks old (7-week starting group) or 8 weeks old (8-week starting group). As an age-matched control, Dahl salt-sensitive rats were consistently placed on normal chow. In these rats, echocardiogram was serially recorded, followed by hemodynamic and histological studies. RESULTS: The 7-week starting rats showed a steep elevation in blood pressure and progressive left ventricular hypertrophy, and fell into overt heart failure at approximately 19 weeks. The development of heart failure was not associated with a decrease in left ventricular midwall fractional shortening or an increase in left ventricular end-diastolic dimension as compared with the age-matched control, which mimics the characteristics of clinically observed isolated diastolic heart failure. The 8-week starting rats showed a gradual rise in blood pressure and less progressive left ventricular hypertrophy, and fell into heart failure at approximately 26 weeks with a decrease in mid-wall fractional shortening and an increase in left ventricular end-diastolic dimension. Hemodynamic and histological studies at failing stage revealed comparable elevation of left ventricular end-diastolic pressure and comparable left ventricular fibrosis in both groups. CONCLUSION: These two different models of overt heart failure may be useful as models of isolated diastolic heart failure and systolic heart failure based on the same hypertensive heart disease, respectively, and may contribute to discrimination of the mechanisms of the development of the two different phenotypes of heart failure.

Animals↗

PubMed2000

Baroreflex control of muscle sympathetic nerve activity after 120 days of 6 degrees head-down bed rest.

To examine how long-lasting microgravity simulated by 6 degrees head-down bed rest (HDBR) induces changes in the baroreflex control of muscle sympathetic nerve activity (MSNA) at rest and changes in responses of MSNA to orthostasis, six healthy male volunteers (range 26-42 yr) participated in Valsalva maneuver and head-up tilt (HUT) tests before and after 120 days of HDBR. MSNA was measured directly using a microneurographic technique. After long-term HDBR, resting supine MSNA and heart rate were augmented. The baroreflex slopes for MSNA during Valsalva maneuver (in supine position) and during 60 degrees HUT test, determined by least-squares linear regression analysis, were significantly steeper after than before HDBR, whereas the baroreflex slopes for R-R interval were significantly flatter after HDBR. The increase in MSNA from supine to 60 degrees HUT was not different between before and after HDBR, but mean blood pressure decreased in 60 degrees HUT after HDBR. In conclusion, the baroreflex control of MSNA was augmented, whereas the same reflex control of R-R interval was attenuated after 120 days of HDBR.

Adult↗

PubMed2000

Head-down bed rest alters sympathetic and cardiovascular responses to mental stress.

Astronauts usually work under much mental stress. However, it is unclear how and whether or not an exposure to microgravity affects physiological response to mental stress in humans. To examine effects of microgravity on vasomotor sympathetic and peripheral vasodilator responses to mental stress, we performed 10 min of mental arithmetic (MA) before and after 14 days of 6 degrees head-down bed rest (HDBR), a ground-based simulation of spaceflight. Total muscle sympathetic nerve activity (MSNA, measured by microneurography) slightly increased during MA before HDBR, and this increase was augmented after HDBR. Calf blood flow (measured by venous occlusion plethysmography) increased and calf vascular resistance (calculated by dividing mean blood pressure by calf blood flow) decreased during MA before HDBR, but these responses were abolished after HDBR. Increases in heart rate and mean blood pressure during MA were not different between before and after HDBR. These findings suggest that HDBR augmented vasomotor sympathoexcitation but attenuated vasodilatation in the calf muscle in response to mental stress.

Adult↗

PubMed2000

Nine months in space: effects on human autonomic cardiovascular regulation.

We studied three Russian cosmonauts to better understand how long-term exposure to microgravity affects autonomic cardiovascular control. We recorded the electrocardiogram, finger photoplethysmographic pressure, and respiratory flow before, during, and after two 9-mo missions to the Russian space station Mir. Measurements were made during four modes of breathing: 1) uncontrolled spontaneous breathing; 2) stepwise breathing at six different frequencies; 3) fixed-frequency breathing; and 4) random-frequency breathing. R wave-to-R wave (R-R) interval standard deviations decreased in all and respiratory frequency R-R interval spectral power decreased in two cosmonauts in space. Two weeks after the cosmonauts returned to Earth, R-R interval spectral power was decreased, and systolic pressure spectral power was increased in all. The transfer function between systolic pressures and R-R intervals was reduced in-flight, was reduced further the day after landing, and had not returned to preflight levels by 14 days after landing. Our results suggest that long-duration spaceflight reduces vagal-cardiac nerve traffic and decreases vagal baroreflex gain and that these changes may persist as long as 2 wk after return to Earth.

Adult↗