Objective: Exposure to microgravity results in postflight cardiovascular deconditioning in astronauts. Vascular oxidative stress injury and mitochondrial dysfunction have been reported during this process. To elucidate the mechanism for this condition, we investigated whether mitochondrial oxidative stress regulates calcium homeostasis and vasoconstriction in hindlimb unweighted (HU) rat cerebral arteries. Methods: Three-week HU was used to simulate microgravity in rats. The contractile responses to vasoconstrictors, mitochondrial fission/fusion, Ca Results: An increase of cytoplasmic Ca Conclusion The present results suggest that mitochondrial oxidative stress enhances cerebral vasoconstriction by regulating calcium homeostasis during simulated microgravity.
Animals ; Calcium/metabolism* ; Cerebral Arteries ; Homeostasis ; Male ; Mitochondria/physiology* ; Myocytes, Smooth Muscle/physiology* ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction/physiology* ; Weightlessness Simulation

BACKGROUNDThe offspring of women with gestational diabetes mellitus (GDM) are prone to macrosomia. However, birth weight is difficult to be correctly estimated by ultrasound because of fetal asymmetric growth characteristics. This study aimed to investigate the correlations between fetal hemodynamics, fetal growth indices in late pregnancy, and birth weight in GDM.

METHODSA total of 147 women with GDM and 124 normal controls (NC) were enrolled in this study. Fetal hemodynamic indices, including the systolic/diastolic ratio (S/D), resistance index (RI), pulsatility index (PI) of umbilical artery (UA), middle cerebral artery (MCA), and renal artery (RA), were collected. Fetal growth indices, including biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length, were also measured by ultrasound. Birth weight, newborn gender, and maternal clinical data were collected.

RESULTSThe independent samples t-test showed that BPD, HC, and AC were larger in GDM than in NC (P < 0.05). Fetal hemodynamic indices of the UA and MCA were lower (P < 0.05), but those of the RA were higher (P < 0.001) in GDM than in NC. Birth weight was higher in GDM than in NC (P < 0.001). Pearson's correlation analysis showed that hemodynamic indices of the UA were negatively correlated with birth weight, BPD, HC, and AC in both groups (P < 0.05). MCA (S/D, PI, and RI) was negatively correlated with birth weight, HC, and AC in GDM (r = -0.164, -0.206, -0.200, -0.226, -0.189, -0.179, -0.196, -0.177, and - 0.172, respectively, P< 0.05), but there were no correlations in NC (P > 0.05). RA (S/D, PI, and RI) was positively correlated with birth weight in GDM (r = 0.168, 0.207, and 0.184, respectively, P< 0.05), but there were no correlations in NC (P > 0.05).

CONCLUSIONFetal hemodynamic indices in late pregnancy might be helpful for estimating newborn birth weight in women with GDM.

Adult ; Birth Weight ; physiology ; Cerebral Arteries ; physiology ; Diabetes, Gestational ; physiopathology ; Female ; Fetal Development ; physiology ; Hemodynamics ; physiology ; Humans ; Infant, Newborn ; Male ; Pregnancy ; Pregnancy Outcome ; Renal Artery ; physiology ; Ultrasonography, Prenatal ; Umbilical Arteries ; physiology

The purpose of the present study is to investigate the effect of isoliquiritigenin (ISL) on the cerebral basilar artery in spontaneously hypertensive rats (SHR). The change of SHR systolic pressure was measured by tail artery pressure measurement instrument before and after ISL intervention. After perfusion with 1 × 10(-5) mol/L phenylephrine (PE), 1 × 10(-5) mol/L PE + 1 × 10(-4) mol/L ISL and 1 × 10(-5) mol/L PE, the diameter of the cerebral basilar artery separated from SHR was measured by pressure myograph. The current of large-conductance calcium-activated potassium (BKCa) channel of SHR single vascular smooth muscle cell (VSMC) was recorded by whole-cell patch-clamp technique and the cGMP levels of basilar artery was evaluated by ELISA. The results showed that 1) after intervention with ISL for 14 days, the systolic pressure of SHR was decreased from (218.3 ± 1.6) mmHg to (119.2 ± 1.9) mmHg (P < 0.01), but there was no difference in systolic pressure between ISL-treated SHR and Wistar-Kyoto (WKY) rat; 2) 1 × 10(-4) mol/L ISL relaxed the SHR cerebral basilar artery (P < 0.01); 3) ISL significantly increased the outward current density of VSMC from SHR cerebral basilar artery (P < 0.01, n = 6), and the effect could be reversed by 1 × 10(-3) mol/L TEA (a BKCa channel inhibitor), but 3 × 10(-4) mol/L 4-AP (a Kv channel inhibitor) had no effect on the enhanced current density induced by ISL in VSMC; 4) 1 × 10(-5) mol/L Methylene blue (a sGC inhibitor) significantly inhibited the ISL-enhanced current density in VSMC (P < 0.05, n = 6); 5) ISL significantly increased the cGMP level of SHR basilar artery (P < 0.05, n = 6). The results suggest that the role of the ISL in relaxing the SHR cerebral basilar artery may be related to its effect in enhancing BKCa current by increasing the levels of cGMP in the VSMC.
Animals ; Basilar Artery ; drug effects ; Blood Pressure ; Cerebral Arteries ; drug effects ; Chalcones ; pharmacology ; Cyclic GMP ; physiology ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; physiology ; Patch-Clamp Techniques ; Potassium Channels, Calcium-Activated ; physiology ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Systole

OBJECTIVETo investigate the difference in membrane current of vascular smooth muscle cells (VSMCs) in brain artery (BA) of spontaneously hypertensive rats (SHR) and Wistar rats.

METHODSWe compared the properties of spontaneous transient outward K+ currents (STOCs), the density and composition of current of VSMCs in BA of SHR and Wistar rats by whole-cell patch clamp technique.

RESULTS(1) When the command voltage was 0, + 20, + 40 and + 60 mV respectively, the current densities of VSMCs in BA of SHR and Wistar rats were significant different (P < 0.01). (2) The whole-cell current of VSMCs was partly inhibited by 1 mmol/L4-AP (voltage-gated K+ channel blocker) or 1 mmol/L TEA (big conductance Ca(2+)-activated K+ channel blocker) respectively. (3) The frequency and amplitude of STOCs in SHR were faster and bigger than those in Wistar rats. 1 mmol/L TEA almostly inhibited the STOCs, but not by 4-AP.

CONCLUSIONThese results suggest that the current densities of VSMCs in BA of SHR and Wistar rats are significant different, the outward current of VSMCs in BA of SHR and Wistar rats are composed by Kv and BK(Ca). SHR express more STOCs mediated by BK(Ca), than Wistar rats.

Animals ; Cerebral Arteries ; cytology ; physiology ; Membrane Potentials ; physiology ; Muscle, Smooth, Vascular ; cytology ; physiology ; Myocytes, Smooth Muscle ; physiology ; Patch-Clamp Techniques ; Potassium Channels, Calcium-Activated ; physiology ; Potassium Channels, Voltage-Gated ; physiology ; Rats ; Rats, Inbred SHR ; Rats, Wistar

OBJECTIVETo investigate the effects of pH0 on the electrophysiological properties of vascular smooth muscle cells (VSMCs) in brain artery of spontaneously hypertension rats (SHR).

METHODSWe studied the effects and the ion mechanism of pH0 on whole-cell membrane current of VSMCs in brain artery of 200 - 250 g SHR by whole-cell patch clamp recordings.

RESULTS1. Acidic pH0 could inhibit the outward current of VSMCs of brain artery in SHR in a voltage-dependent manner. It induced a more pronounced inhibition of the outward current from 0 to + 60mV; 2. In the presence of 1 mmol/L TEA, the inhibition of acidic pH0 on the outward current of VSMCs of brain artery was inhibited.

CONCLUSIONThe changes of outward current of VSMCs of brain artery in SHR induced by pH0 may be connected with BKCa channel.

Animals ; Cerebral Arteries ; cytology ; Electrophysiological Phenomena ; Extracellular Fluid ; physiology ; Hydrogen-Ion Concentration ; Muscle, Smooth, Vascular ; physiology ; Rats ; Rats, Inbred SHR

Some studies suggest that the calcium channels and rennin-angiotensin system (RAS) play pivotal roles in the region-specific vascular adaptation due to simulated weightlessness. This study was designed to clarify if angiotensin II (Ang II) was involved in the adaptational change of the L-type calcium channel (Ca(L)) in the cerebral arterial vascular smooth muscle cells (VSMCs) under simulated weightlessness. Tail suspension (SUS) for 3 d was used to simulate immediate early cardiovascular changes to weightlessness. Then VSMCs in cerebral basilar artery were enzymatically isolated using papain, and Ca(L) current (barium instead of calcium as current carrier) in VSMCs was measured by whole-cell patch-clamp techniques. The results showed that 3-day simulated weightlessness significantly increased current density of Ca(L). However, I-V relationships of normalized peak current densities and steady-state activation curves of Ca(L) were not affected by simulated weightlessness. Although Ang II significantly increased current densities of Ca(L) in both SUS and control rats, the increase of Ca(L) current density in SUS rats was much more than that in control rats. These results suggest that 3-day simulated weightlessness induces the adaptational change of Ca(L) in cerebral VSMCs including increased response to Ang II, indicating that Ang II may play an important role in the adaptational change of cerebral arteries under microgravity.
Adaptation, Physiological ; Angiotensin II ; physiology ; Animals ; Calcium Channels, L-Type ; physiology ; Cerebral Arteries ; cytology ; physiology ; Hindlimb Suspension ; Male ; Muscle, Smooth, Vascular ; cytology ; physiology ; Myocytes, Smooth Muscle ; metabolism ; physiology ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Weightlessness Simulation

Laser scanning confocal microscopy (LSCM) and whole-cell perforated patch-clamp techniques were combined to study simultaneously the changes of intracellular signal molecules and membrane currents. Intracellular calcium transients and spontaneous transient outward currents (STOCs) were recorded simultaneously in freshly isolated mouse cerebral artery smooth muscle cells. The cells loaded with fluo-4/AM were scanned with the confocal line-scan mode. Triggering voltage pulses derived from an EPC-10 patch clamp amplifier triggered the confocal line scan. The results showed that STOCs and intracellular calcium transients could be simultaneously recorded in the same cell. This technique will be useful in studies of diseases caused by impairments of intracellular Ca(2+) signaling and related ionic channel activities, or vice versa.
Animals ; Calcium Signaling ; Cerebral Arteries ; cytology ; Mice ; Myocytes, Smooth Muscle ; physiology ; Patch-Clamp Techniques

The aim of the present study was to further elucidate the mechanisms of vascular adaptation to microgravity and its gravity-based countermeasure by a biomechanical approach. Active (the dissected vessel segment was superfused with PPS) and passive (while it was superfused with Ca(2+)-free PPS) biomechanical properties of mesenteric third-order small arteries and middle cerebral arteries isolated from 3-day simulated microgravity (SUS), countermeasure (STD, daily 1 h of -G(x) gravitation), and control (CON) groups of rats were studied. The following mechanical parameters were calculated: the overall stiffness parameter of passive vessels (beta), circumferential stress (sigma(theta))-strain (epsilon(theta)) relationship, and pressure-dependent incremental elastic modulus (E(inc,p)) of both active and passive vessels, and vascular smooth muscle (VSM) activity-dependent incremental modulus (E(inc,a)). Results from the analysis of active biomechanical properties revealed the contribution of vascular smooth muscle (VSM) tone during the early adaptation to microgravity: (1) For mesenteric small arteries, active circumferential sigma(theta) -epsilon(theta) curve of SUS group was comparable with that of the passive vessels, indicating that the function of VSM to restore the normal stress distribution is compromised; however, this mal-adaptation was fully prevented by the countermeasure of daily 1 h of -G(x) gravitation; (2) For the middle cerebral arteries, active circumferential sigma(theta) -epsilon(theta) relation of SUS group was shifted to the left side of the passive curve and epsilon(theta) was kept at a nearly constant level with the corresponding sigma(theta) being at its normal range; furthermore, the enhanced myogenic tone responsiveness was not prevented by daily short-duration -G(x). Analysis of the passive biomechanical properties has suggested remodeling changes in matrix components of different types of vessels, which might be significant if the exposure duration was further prolonged. In brief, studies of vascular biomechanics are of particular importance in elucidating the mechanisms underlying vascular adaptation to microgravity and its gravity-based countermeasure.
Animals ; Biomechanical Phenomena ; Mesenteric Arteries ; physiology ; Middle Cerebral Artery ; physiology ; Muscle, Smooth, Vascular ; physiology ; Pressure ; Rats ; Weightlessness Simulation

INTRODUCTIONAdults with obstructive sleep apnoea (OSA) are well documented to be at high risk for cardiovascular abnormalities. Growing evidence suggests that OSA is also associated with cardiovascular consequences in children. The purpose of this review is to examine the available data on this association in children.

METHODSPrimary studies were extracted from a MEDLINE search limited to those published between 1970 and 2008. The keywords used included child, sleep disordered breathing, sleep apnoea, snoring, blood pressure and hearts. The relevant articles were selected by consensus between 2 authors.

RESULTSThe results suggested that OSA was consistently associated with hypertension. Meta-analysis of risk of hypertension in those with high apnoea-hypopnoea index was undertaken. A combined odds ratio equal to 3.15 was found (95% confidence interval, 2.01 to 4.93). There was evidence for increased sympathetic activation, decreased arterial distensibility and ventricular hypertrophy in children with OSA.

CONCLUSIONChildhood OSA is associated with blood pressure dysregulation. The association of OSA with other cardiovascular morbidities requires further study in view of the limited data available currently.

Atherosclerosis ; physiopathology ; Blood Pressure ; physiology ; Cardiovascular System ; physiopathology ; Cerebral Arteries ; physiopathology ; Child ; Endothelium, Vascular ; physiopathology ; Heart Rate ; physiology ; Humans ; Hypertension ; physiopathology ; Hypertrophy, Left Ventricular ; physiopathology ; Pulmonary Heart Disease ; physiopathology ; Regional Blood Flow ; Sleep Apnea, Obstructive ; complications ; physiopathology ; Ventricular Function

OBJECTIVETo explore the changes of endostatin (a strong anti-angiogenesis factor) and vascular endothelial growth factor (VEGF) in the brain tissues of rabbits following cerebral ischemia induced by middle cerebral artery occlusion (MCAO).

METHODSTwenty-four New Zealand white rabbits were randomly divided into 5 groups: control (n = 5), sham-operation (n = 4), 2-hour ischemia (n = 5), 24-hour ischemia (n = 5), and 48-hour ischemia (n = 5). The expression of VEGF and endostatin were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. In situ hybridization was used to characterize the expression of mRNA for the endostatin.

RESULTSBoth the protein (at least 50%, P < 0.01) and mRNA (at least 70%, P < 0.05) of endostatin increased significantly in the ischemic brain tissues after MCAO compared with the control group. VEGF increased at least 270% in the brain after cerebral ischemia (P < 0.05).

CONCLUSIONCerebral ischemia leads to an up-regulation of endostatin in the brain, which is not associated with the increase of VEGF in the brain. The increase of endostatin may serve as a deleterious mechanism for ischemic injury through blocking angiogenesis.

Animals ; Brain ; metabolism ; physiopathology ; Brain Ischemia ; genetics ; metabolism ; physiopathology ; Cerebral Arteries ; metabolism ; Endostatins ; genetics ; metabolism ; Endothelium, Vascular ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Immunohistochemistry ; In Situ Hybridization ; Infarction, Middle Cerebral Artery ; genetics ; metabolism ; physiopathology ; Male ; Neovascularization, Physiologic ; physiology ; Rabbits ; Up-Regulation ; physiology ; Vascular Endothelial Growth Factor A ; metabolism