Advances in the construction and application of konjac glucomannan-based delivery systems.

Konjac glucomannan (KGM) has been widely used to deliver bioactive components due to its naturalness, non-toxicity, excellent biodegradability, biocompatibility, and other characteristics. This review presents an overview of konjac glucomannan as a matrix, and the types of konjac glucomannan-based delivery systems (such as hydrogels, food packaging films, microencapsulation, emulsions, nanomicelles) and their construction methods are introduced in detail. Furthermore, taking polyphenol compounds, probiotics, flavor substances, fatty acids, and other components as representatives, the applied research progress of konjac glucomannan-based delivery systems in food are summarized. Finally, the prospects for research directions in konjac glucomannan-based delivery systems are examined, thereby providing a theoretical basis for expanding the application of konjac glucomannan in other industries, such as food and medicine.

Using Pb Isotope to Quantify the Effect of Various Sources on Multi-Metal Polluted soil in Guiyu.

Guiyu is known as one of the largest e-waste disposal and recycling sites in China, which suffers greatly from heavy metal pollution. By evaluating the concentrations and distribution of 21 metal elements with Principal Component Analyses (PCA), five principal components were identified, which accounted for 70.4% of the information of the initial data matrix, including one e-waste recycling source, two geological sources, one source of human activities and one ocean aerosol source. Among them, the source of human activities cannot be detailed only by PCA. By using Pb isotope, the unexplained source was judged as battery sludge. Combining 21 metallic and metalloid element datasets with Pb isotope concentrations is more accurate and effective to identify uncertain sources in soil.

Reversible Immortalization Enables Seamless Transdifferentiation of Primary Fibroblasts into Other Lineage Cells.

Fibroblasts can be transdifferentiated directly into other somatic cells such as cardiomyocytes, hematopoietic cells, and neurons. An advantage of somatic cell differentiation without first generating induced pluripotent stem cells (iPSCs) is that it avoids contamination of the differentiated cells with residual iPSCs, which may cause teratoma. However, since primary fibroblasts from biopsy undergo senescence during repeated culture, it may be difficult to grow transdifferentiated cells in sufficient numbers for future therapeutic purposes. To circumvent this problem, we reversibly immortalized primary fibroblasts by using the piggyBac transposon to deliver the human telomerase reverse transcriptase (hTERT) gene hTERT plus SV40 Large T. Both approaches enabled fibroblasts to grow continuously without senescence, and neither caused teratoma formation in immunodeficient mice. However, fibroblasts immortalized with hTERT plus SV40 large T antigen accumulated chromosomal rearrangements, whereas fibroblasts immortalized with hTERT retained the normal karyotype. To transdifferentiate hTERT-immortalized fibroblasts into other somatic lineage cells, we transiently transfected them with episomal OCT4 and cultured them under neural cell growth condition with transposase to remove the transposon. Tripotent neural progenitor cells were seamlessly and efficiently generated. Thus, reversible immortalization of primary fibroblasts with hTERT will allow potential autologous cell-based therapeutics that bypass and simulate iPSC generation.

Effect of Chinese herbal medicine on vascular functions during 60-day head-down bed rest.

PURPOSE: Chinese herbal medicine is a promising countermeasure against cardiovascular dysfunction associated with a sedentary lifestyle. We examined the impact of the Chinese herb, Taikong Yangxin, on the micro- and macrovascular dysfunction associated with a 60-day bed rest. METHODS: Fourteen healthy men were randomly divided into two groups: those given herbal supplement, and the control group; the two groups underwent a 60-day bed rest. The macrovasculature was assessed by sonography. Skin microvascular functions were assessed with laser Doppler. The plasma level of endothelial microparticles (EMPs), markers of endothelial injury, was determined. RESULTS: Bed rest induced a 33 % decrease in the femoral artery diameter and compliance whereas carotid wall thickness, diameter, and compliance remained unchanged. The early phase of endothelium-dependent vasodilation to ACh was unmodified by bed rest, while the late phase was reduced by 30 % along with a twofold increase in EMPs. In those given Taikong Yangxin, the early phase was amplified by 2.5-fold, and the effects of bed rest on the late phase were prevented. CONCLUSION: These findings indicate that Taikong Yangxin ameliorates endothelium-dependent vasodilation, likely by improving the NO pathway. The study suggests Taikong Yangxin as a new countermeasure to prevent the changes in microvascular function induced by physical inactivity.

Bovine prolactin elevates hTF expression directed by a tissue-specific goat ß-casein promoter through prolactin receptor-mediated STAT5a activation.

Prolactin promotes the expression of exogenous human transferrin gene in the milk of transgenic mice. To elucidate this, a recombinant plasmid of bovine prolactin plus human transferrin vector was co-transfected into cultured murine mammary gland epithelial cells. Prolactin-receptor antagonist and shRNA corresponding to prolactin-receptor mRNA were added into the cell culture mixture to investigate the relations between prolactin-receptor and human transferrin expression after bovine prolactin inducement. Levels of human transferrin in the supernatants were increased under the presentation of bovine prolactin (from 1,076 ± 115 to 1,886 ± 114 pg/ml). With the treatment of prolactin-receptor antagonist or shRNA, human transferrin in cells was declined (1,886 ± 113 vs. 1,233 ± 85 pg/ml or 1,114 ± 75 pg/ml, respectively). An inverse correlation was found between the dosage of prolactin-receptor antagonist and expression level of human transferrin. Real-time qRT-PCR analysis showed that the relative level of signal transducer and activator of transcription 5a (STAT5a) transcript in transfected cells correlated with expression levels of human transferrin in the supernatant of the same cells. Bovine prolactin thus improved the expression of human transferrin through such a possible mechanism that bovine prolactin activated STAT5a transcription expression via combined with prolactin-receptor and suggest a potential utility of the bovine prolactin for efficient expression of valuable pharmaceutical proteins in mammary glands of transgenic animals.

Adjusting the attB site in donor plasmid improves the efficiency of ΦC31 integrase system.

ΦC31 integrase, a site-specific recombinase, can catalyze integration of circular DNA bearing attB site into pseudo attP sites in mammalian genomes. However, the integration efficiency mediated by integrase is relatively low. Our study centered on the investigation of the impact of the position, orientation, and number of attBs in the donor plasmid on the efficiency of ΦC31 integrase system. Donor plasmids bearing various types of attBs (including forward and reverse directions, tandem, and intersperse) and reporter enhanced green fluorescent protein (EGFP) were constructed. The plasmids plus helper plasmid encoding integrase were co-transfected into HeLa cells. After G418 selection, the resistant cell colonies were counted for calculating chromosomal integration frequency. EGFP expression was detected by fluorescence-activated cell sorter and enzyme-linked immunosorbent assay analysis. The results showed that efficiency of integration mediated by integrase accounted for 70% ± 7.1% of total integration events in the transfected HeLa cells. Compared with a forward orientation of attB in donor plasmid, a reverse direction of attB or interspersed attBs showed 1.5- or 2.8-fold increase in integration efficiency, respectively, while tandem attBs in donor plasmids caused a decreased efficiency of integration. We conclude that the adjustment of attB sites in donor plasmids may be of value for gene therapy and routine genetic engineering by using ΦC31 integrase system.

Peripheral arterial and venous response to tilt test after a 60-day bedrest with and without countermeasures (ES-IBREP).

UNLABELLED: We quantified the impact of 60-day head-down bed rest (HDBR) with countermeasures on arterial and venous response to tilt. METHODS: Twenty-one males: 7 control (Con), 7 resistive vibration exercise (RVE) and 7 Chinese herb (Herb) were assessed. Subjects were identified as finisher (F) or non-finishers (NF) at the post-HDBR 20-min tilt test. The cerebral (MCA), femoral (FEM) arterial flow velocity and leg vascular resistance (FRI), the portal vein section (PV), the flow redistribution ratios (MCA/FEM; MCA/PV), the tibial (Tib), gastrocnemius (Gast), and saphenous (Saph) vein sections were measured by echography and Doppler ultrasonography. Arterial and venous parameters were measured at 3-min pre-tilt in the supine position, and at 1 min before the end of the tilt. RESULTS: At post-HDBR tilt, MCA decreased more compared with pre-HDBR tilt in the Con, RVE, and Herb groups, the MCA/FEM tended to decrease in the Con and Herb groups (not significant) but remained stable in the RVE gr. FRI dropped in the Con gr, but remained stable in the Herb gr and increased in the RVE gr. PV decreased less in the Con and Herb groups but remained unchanged in the RVE gr. MCA/PV decreased in the Con and Herb groups, but increased to a similar extent in the RVE gr. Gast section significantly increased more in the Con gr only, whereas Tib section increased more in the Con and Herb groups but not in the RVE gr. The percent change in Saph section was similar at pre- and post-HDBR tilt. CONCLUSION: In the Con gr, vasoconstriction was reduced in leg and splanchnic areas. RVE and Herb contributed to prevent the loss of vasoconstriction in both areas, but the effect of RVE was higher. RVE and Herb contributed to limit Gast distension whereas only RVE had a protective effect on the Tib.

Whole-body vibration and resistance exercise prevent long-term hindlimb unloading-induced bone loss: independent and interactive effects.

Skeletal unloading induced by disuse or immobilization causes a decrease in bone mass and strength. We investigated the relationship between whole-body vibration (WBV) and resistance exercise (RE) in preventing bone loss induced by 8-week hindlimb unloading in young male rats. Sixty male Wistar rats were assigned randomly to 6 groups: age-matched control group (CON, n = 10), hindlimb unloading group (HU, n = 10), hindlimb unloading + standing group (HU + ST, n = 10), hindlimb unloading + WBV group (HU + WBV, n = 10), hindlimb unloading + RE group (HU + RE, n = 10) and hindlimb unloading + WBV + RE group (HU + WBV + RE, n = 10). After 8-week hindlimb unloading, micro-CT scanning and three-point bending test were performed in the femur. Sera were collected for analysis of bone formation and resorption markers. Compared with HU group, WBV, RE and the combination of WBV and RE (WBV + RE) significantly improved (P < 0.01) one repetition maximum (1RM) (expressed as the percentage change from baseline, HU: -23%, HU + WBV: 21%, HU + RE: 48%, HU + WBV + RE: 51%), and maintained (P < 0.05) cancellous volumetric bone mineral density (vBMD) and trabecular structure. No difference of cortical vBMD was found among all groups (P > 0.05). WBV had no effects on biomechanical properties of the femur diaphysis (P > 0.05). RE and WBV + RE significantly increased maximum load and cross-sectional moment of inertia of the femur diaphysis in hindlimb unloading rats (P < 0.05). There was an interaction between WBV and RE in improving cancellous bone. These results demonstrate that WBV and RE interactively maintain cancellous structure and vBMD, and independently partially mitigate the reduction of bone strength in long-term hindlimb unloading rats.

Temporal artery flow response during the last minute of a head up tilt test, in relation with orthostatic intolerance after a 60 day head-down bedrest.

OBJECTIVE: Check if the Temporal flow response to Tilt could provide early hemodynamic pattern in the minutes preceding a syncope during the Tilt test performed after a 60-d head down bedrest (HDBR). METHOD: Twenty-one men divided into 3 groups [Control (Con), Resistive Vibration (RVE) and Chinese Herb (Herb)] underwent a 60 day HDBR. Pre and Post HDBR a 20 min Tilt identified Finishers (F) and Non Finishers (NF). Cerebral (MCA), Temporal (TEMP), Femoral (FEM) flow velocity, were measured by Doppler during the Tilt. Blood pressure (BP) was measured by arm cuff and cardiopress. RESULTS AND DISCUSSION: Four of the 21 subjects were NF at the post HDBR Tilt test (Con gr:2, RVE gr: 1, Herb gr: 1). At 1 min and 10 s before end of Tilt in NF gr, FEM flow decreased less and MCA decreased more at post HDBR Tilt compared to pre (p<0.05), while in the F gr they changed similarly as pre. In NF gr: TEMP flow decreased more at post HDBR Tilt compared to pre, but only at 10 s before the end of Tilt (P<0.05). During the last 10 s a negative TEMP diastolic component appeared which induced a drop in mean velocity until Tilt arrest. CONCLUSION: The sudden drop in TEMP flow with onset of a negative diastolic flow preceding the decrease in MCA flow confirm that the TEMP vascular resistance respond more directly than the cerebral one to the cardiac output redistribution and that this response occur several seconds before syncope.

Low-magnitude whole body vibration with resistive exercise as a countermeasure against cardiovascular deconditioning after 60 days of head-down bed rest.

Whole body vibration with resistive exercise is a promising countermeasure against some weightlessness-induced dysfunctions. Our objective was to study whether the combination of low-magnitude whole body vibration with a resistive exercise can prevent the cardiovascular deconditioning induced by a nonstrict 60-day head-down bed rest (Earth Star International Bed Rest Experiment Project). Fourteen healthy men participated in this study. We recorded electrocardiograms and blood pressure waves by means of a noninvasive beat-by-beat measurement system (Cardiospace, integrated by Centre National d'Etudes Spatiales and Astronaut Center of China) during an orthostatic test (20 min of 75-degree head-up tilt test) before and immediately after bed rest. We estimated heart rate, blood pressure, cardiac output, stroke volume, total peripheral resistance, baroreflex sensitivity, and heart rate variability. Low-magnitude whole body vibration with resistive exercise prevented an increase of the sympathetic index (reflecting the sympathovagal balance of cardiac autonomic control) and limited the decrease of the spontaneous baroreflex sensitivity induced by 60 days of head-down bed rest. However, this countermeasure had very little effect on cardiac hemodynamics and did not improve the orthostatic tolerance. This combined countermeasure did not efficiently prevent orthostatic intolerance but prevents changes in the autonomic nervous system associated with cardiovascular deconditioning. The underlying mechanisms remain hypothetical but might involve cutaneous and muscular mechanoreceptors.

[Progress of research on human tolerance to impact acceleration].

Impact acceleration is one of the factors to which human body is exposed in aerospace exploring. When the impact level is greater than human tolerance, it usually results in human injuries which may be fatal. Therefore, in order to reduce or avert the risk of serious injury from crash impact, human tolerance to impact acceleration is a crucial consideration in aircraft since the beginning of aviation. The study on human tolerance to impact acceleration has become a cynosure in the realm of modern biomechanics. So this paper reviews the progress of the researches.

Effect of thigh cuffs on haemodynamic changes of the middle cerebral artery and on orthostatic intolerance induced by 10 days head-down bed rest.

Thigh cuffs are used by cosmonauts to limit fluid shift during space flight, but the appropriate level of cuff pressure and the duration of application to optimize their beneficial effects require further detailed investigations. In the present study, 10 days head-down tilt (HDT) bed rest was performed to assess the effects of thigh cuffs (40 mmHg, 10 h/day) on haemodynamic changes of the middle cerebral artery (MCA) and on orthostatic tolerance in six healthy male volunteers. Another six healthy male volunteers without thigh cuffs served as the control group. Haemodynamic parameters of the MCA were measured using transcranial Doppler. Orthostatic tolerance was assessed before and after HDT. After HDT, the mean upright time in the control and thigh cuff groups was 14.0 +/- 4.1 and 19.2 +/- 0.7 min, respectively. Compared with values before HDT, the percentage increase in heart rate from baseline in the upright position after HDT was significantly higher in the control group and the percentage change from baseline of mean diastolic arterial blood decreased more after HDT in this group. In the control group, systolic blood velocity (Vs) and mean blood velocity (Vm) of the right MCA decreased significantly during HDT. In the thigh cuffs group, the Vs of the right MCA decreased significantly on Days 3 and 7 of HDT and the Vm of the right MCA decreased significantly on Day 7 of HDT. The results indicate that daily use of thigh cuffs during 10 days of HDT does not completely prevent the decrease in haemodynamics of the right MCA, but is effective in preventing orthostatic intolerance.

[Repeated body position change training can improve human head-down tilt tolerance].

AIM: To verify the hypothesis that repeated body position change training can improve human head-down tilt (HDT) tolerance. METHODS: Six young healthy subjects were trained with repeated position change for 9 times and 11 days according to protocol of alternative head-down and head-up tilts, each time of training lasted for about 35 min. Their HDT tolerance (- 30 degrees/30 min) were determined before and after training. RESULTS: (1) Compared with the data before training, subjects' symptom scores during HDT test after training decreased significantly (6.00 +/- 3.79 vs 1.00 +/- 0.63, P < 0.05), magnitude of the decreased heart rate increased significantly (-0.6 +/- 2.5 vs -4.4 +/- 3.6, P < 0.01). (2) Before training, blood flow volume of internal jugular vein (IJV) during HDT decreased significantly and that of internal carotid artery (ICA) increased significantly at the beginning period of HDT compared with pre-HDT (P < 0.01), while blood flow volume of the common carotid artery (CCA) presented increasing trend. After training, there was no significant difference in blood flow volume of IJV between during HDT and pre-HDT, that of ICA and CCA presented decreasing trend in the final period of HDT compared with Pre-HDT. CONCLUSION: Repeated body position change training can improve human head-down tilt tolerance. And its main causation is that headward shift of blood volume is restrained to some extend during HDT after training.

Compliance changes in femoral veins of rabbits after 21 days of simulated weightlessness.

Increased venous compliance in lower limbs may be contributed to postflight orthostatic intolerance; however, direct animal studies to address the changes of venous compliance to microgravity have been rare. The purpose of this study was to determine compliance changes in femoral veins of rabbits after 21 days of head-down rest. Head-down rest -20 dgrees rabbit model was used to simulate weightlessness. 24 healthy male New Zealand Rabbits were randomly divided into 21 days of head-down rest group (HDR), horizontal immobilization group (HIG) and Ctrl group (Ctrl), with 8 in each. We constructed pressure-volume relationships from femoral veins in vivo for all groups after simulation by changing the venous internal volume and measuring the corresponding pressure. Microstructure of femoral vein wall in 3 groups was observed. Compared among the groups, the corresponding intravenous pressure of Ctrl was the highest when intravenous volume was expanded and HDR was the lowest. The parameter 3 , and P 2 in quadratic equations of femoral venous P-V relationship of HDR group were significantly higher than these values of HIG group and Ctrl group. The structure of femoral vein wall of HDR rabbits changed significantly, outlines of some endothelium cells (EC) became short and columnar or cubic, some of EC fell off and smooth muscle layer became thinner. These results indicate that, the femoral venous compliance increased after weightlessness simulation. This may partially underlie the mechanism of orthostatic hypotension seen in astronauts during an orthostatic stress after exposure to microgravity.

[Dynamic responses of human body and human surrogate to different impacts under 30 degrees supine position].

OBJECTIVE: To study the difference between the dynamic responses of human body and human surrogate under 30 degrees supine position, and to discuss impact probability of substituting human body with human surrogate in impact tests. METHOD: Five volunteers experienced half-sine impact pulses, averaged 4.76, 8.96, 11.33 G, lasting for 40-60 ms on an impact tower. The human surrogate was exposed to half-sine impact pulses, averaged 6.77, 10.39, 16.93, 21.11, 24.98, 31.11 G, lasting for 40-60 ms, two times for each G level. ECG changes of the volunteers were continuously monitored before, during and after each impact. RESULT: Output responses at forehead and chest of human body and human surrogate increased with input increments. But there was obvious difference of the dynamic responses between human body and the surrogate to impact of low G levels. Heart rate of each volunteer had temporary increase during the process of impact, and returned to normal level soon after the impact. CONCLUSION: There is difference in a certain extend between the dynamic responses of human body and human surrogate. The ECG changes are induced mainly by mental stress during process of impact.

The role of ERK in phasic and tonic contractile responses in rat femoral arteries after hindlimb unloading.

The present study tested the hypothesis that the role of ERK in phasic and tonic contractile responses is declined by hindlimb unloading (HU) in rat femoral arteries. Male Wistar rats were randomised into HU and Control group (n=7). After 14d, the femoral arteries were isolated and cut into 3-mm ring segments. In the absence or presence of PD98059(MEK inhibitor), contractile response to NE(10μM) was measured in Krebs solution in a tissue bath at 37°C, isometric tension were recorded with Powerlab system. The area under curve (AUC), phasic and tonic contractile responses between two groups were compared. After 14d-HU, the AUC, phasic and tonic NE-induced contractile responses were declined compared with controls. PD98059 did not affect the AUC in arteries from HU, but significantly decreased the AUC in arteries from control (100±7.1% vs. 61.18±11.3%, P<0.05). In contrast to control, the inhibitory ratio of PD98059 was significantly lower in phasic (7.42±3.24% vs. 33.59± 9.19%, P=0.0198) and tonic (26.93±3.78% vs. 46.75±5.67%, P=0.0131) contractile responses of HU group. Moreover, the inhibitory ratio of PD98059 wasn't significantly different between the phasic and tonic contractile responses in control group (P=0.2464). But for HU group, the difference was statistically significant (P=0.002). We demonstrated that the role of ERK was declined in both phasic and tonic contractile responses in rat femoral arteries after hindlimb unloading. Simulated microgravity induced by HU may attenuate the contractile responses of femoral arteries by inhibiting the role of ERK in thick and thin filament regulatory pathways.

Effect of lower-body negative pressure on cerebral blood flow velocity during 21 days head-down tilt bed rest.

BACKGROUND: The purpose of this study was to investigate cerebral blood flow (CBF) velocity in humans during 21 days of head-down tilt (HDT) bed rest with and without lower-body negative pressure (LBNP). MATERIAL/METHODS: Twelve healthy male volunteers were exposed to -6 degrees HDT bed rest for 21 days. Six subjects received -30 mmHg LBNP sessions for 1 h per day from the 1st to the 7th day and from the 15th to the 21st day of HDT, and six others served as controls. CBF velocity was measured by use of the transcranial Doppler technique in the right middle cerebral artery before and during HDT. RESULTS: In the control group, mean and systolic CBF velocities decreased on day 1 of HDT compared with the pre-HDT value, and dropped further on day 3 of HDT, then remained significantly below the pre-HDT baseline on days 7 and 10 of HDT, and reached a minimum value on day 21 of HDT. In the LBNP group, mean and systolic CBF velocities decreased significantly on day 1 of HDT compared with the pre-HDT value, and remained lowered throughout HDT. Diastolic CBF showed no significant change throughout HDT in both groups. There were no significant differences in these parameters between the two groups. CONCLUSIONS: The results of this study suggest that CBF velocity is reduced during 21 days of HDT, and brief daily LBNP sessions used in the first and last weeks of 21-day HDT bed rest does not improve CBF velocity.

[Changes of ERK1/2 in femoral arteries of tail-suspended rats and their effects on contractility].

OBJECTIVE: To study changes of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in femoral arteries of tail-suspended rats and their effects on contractility. METHOD: Microgravity was simulated by elevating the hindquarters of Wistar rats to produce hindlimb unweighting (HU). In the absence or presence of prazosin and PD98059 respectively, isometric tension of vessel rings from femoral arteries in response to norepinephrine (NE) was determined by in vitro perfusion technique; Basal total ERK1/2 level and phosphorylated ERK1/2 level stimulated by norepinephrine in the absence or presence of prazosin and PD98059 respectively were detected by Western blotting-enhanced chemically lightening system. RESULT: The maximal contractile response to NE was significantly lower in femoral arterial rings from 14 day-HU rats as compared with those in control rats. PD98059 caused a marked inhibition of NE-induced maximum contractile response in both control and HU femoral arterial rings. Moreover, the effect of inhibition was more significant in control rats than that in HU rats. Prazosin caused a right shift of the concentration-response curves (CRCs) to NE in both control and HU rats, but no difference was found between the two groups for the PA2 of prazosin calculated by Schild analysis, which showed that the sensitivity of alpha1 adrenoceptor was not changed by HU. After 7d-recovery, the difference of contractile response of femoral arterial rings to NE between recovered group and control group was nonsignificant. Data from Western blotting showed that basal total ERK1/2 levels were elevated in femoral arterial rings from 14d-HU rats as compared with those in control rats, but the levels of basal and NE-stimulated phosphorylated ERK1/2 were higher in control as compared with HU rats. After 7d recovery, the basal total ERK1/2 level and phosphorylated ERK1/2 level were not different from control. CONCLUSION: Microgravity simulated by 14d-HU can induce abnormality of MAPK/ERK pathway, which may contribute to declined contractile response of femoral vessel rings to NE.

[Role of ROK in contraction of rat femoral arteries after 14 d tail suspension].

OBJECTIVE: To determine the role of Rho associated kinase (ROK) in contraction of rat femoral arteries after 14 d tail suspension. METHOD: Male Wistar rats were randomly divided into control group (CON) and 14 d -30 degrees tail suspension group (TS14d). Analysis was performed on the contractile responses of perfused femoral arterial rings from both TS14d and CON rats to KCl, phenylephrine (PE), and U-46619 in the presence of Y-27632. RESULT: Arterial rings from TS14d rats displayed a reduced contractile response to KCl and PE but not significantly to U-46619. In the response to KCl, Y-27632 caused a concentration-dependent relaxation and significantly larger decrease of contraction in tissues from TS14d rats. Y27632 nearly abolished the tonic component of KCl-induced contraction when its dose was increased from 10(-6)mol/L to 10(-5) mol/L. It had also an inhibitive effect on the PE and U-46619-induced contraction and caused significantly larger decrease in U-46619 but not in KCl or PE induced contraction in tissues from TS14d rats. CONCLUSION: ROK activity may be enhanced and play a compensational role in rat femoral arteries after TS14d.