Adsorptive removal of sulfonamide antibiotics in livestock urine using the high-silica zeolite HSZ-385.

The adsorptive removal of seven sulfonamide antibiotics using the high-silica zeolite HSZ-385 from distilled water, synthetic urine and real porcine urine was investigated. The pH greatly affected the adsorption efficiency, and the amounts of all sulfonamide antibiotics adsorbed on HSZ-385 decreased at alkaline conditions compared with that at neutral conditions. During storage, the pH and ammonium-ion concentration increased with urea hydrolysis for porcine urine. We clarified that the adsorption efficiency of sulfonamides in synthetic urine was equivalent to that in distilled water, suggesting that adsorption behavior was not affected by coexistent ions. HSZ-385 could adsorb sulfonamide antibiotics in real porcine urine even though the non-purgeable organic carbon concentration of porcine urine was 4-7 g/L and was two orders of magnitude higher than those of sulfonamides (10 mg/L each). Moreover, the adsorption of sulfonamides reached equilibrium within 15 min, suggesting that HSZ-385 is a promising adsorbent for removing sulfonamides from porcine urine.

High levels of anandamide, an endogenous cannabinoid, block the growth of sheep preimplantation embryos by inducing apoptosis and reversible arrest of cell proliferation.

BACKGROUND: The process of implantation is mediated by various molecules, one of which is anandamide (AEA), a lipid signalling ligand belonging to the family of endocannabinoids. AEA exerts its effects on implantation by binding to the Type 1 Cannabinoid Receptor (CB1-R), expressed in both blastocysts and uterus. We wanted to know whether the endocannabinoid signalling system was present also in the sheep reproductive tract and which kind of effect(s) AEA had on the development of sheep blastocysts in vitro. METHODS: We analysed the expression and activity of the endocannabinoid system in sheep reproductive tracts and blastocysts. Hatched sheep blastocysts were then exposed to AEA and its effect(s) were determined by TUNEL assay and by measuring the rate of necrosis and 5-bromo-deoxyuridine incorporation. RESULTS: We show that the AEA signalling system is present in sheep and that high concentrations of AEA induce apoptosis and inhibit cell proliferation via a CB1-R-dependent mechanism. Indeed, AEA effects were blocked when sheep blastocysts were cultured in the presence of the CB1-R antagonist SR161417A. Moreover, AEA inhibition of cell proliferation was reversible, as arrested embryos resumed a normal growth rate upon AEA removal from the medium. CONCLUSIONS: Our results suggest that disturbed regulation of AEA signalling via CB1-R may be associated with pregnancy failure. AEA could lower the quality of blastocysts by inducing apoptosis and inhibiting cell proliferation, thus making them incompetent for implantation.

Tissue distribution of human gliostatin/platelet-derived endothelial cell growth factor (PD-ECGF) and its drug-induced expression.

Human tissue contents of gliostatin/platelet-derived endothelial cell growth factor (PD-ECGF) and its drug-induced expression in tumor cells were currently examined by a sandwich enzyme immunoassay (EIA) system and a reverse transcription-polymerase chain reaction (RT-PCR) method. Gliostatin/PD-ECGF was found to distribute in rather ubiquitous than specific human tissues and organs, with a relatively high levels in the tissues of digestive system (esophagus and rectum), brain, spleen, bladder and lung, but not in gall bladder, aorta, muscle, fat and kidney. Most of examined human tumor cell lines showed 4- or 5-fold higher contents (21.5 +/- 3.9 ng/mg protein) than normal tissue contents (4.4 +/- 1.1 ng/mg protein) on the average. While gliostatin/PD-ECGF is known to lack a signal sequence, some tumor cells (A431 and MKN74) appeared to release it into the conditioned medium. Expression of gliostatin/PD-ECGF in epidermoid carcinoma cell (A431) and stomach cancer cell (MKN45) was induced by dibutyryl cyclic AMP and phorbol ester, and uniquely in MKN45 by hydrocortisone. In particular, this hydrocortisone specifically caused an increase of the apparent secretion of MKN74 without its cytotoxic effects, suggesting a possible secretion of gliostatin/PD-ECGF in the restricted but not universal cell line. Biological significance on the chemical induction of gliostatin/PD-ECGF in tumor cells and on its extracellular secretion are discussed.

Establishment of an enzyme immunoassay system for gliostatin/platelet-derived endothelial cell growth factor (PD-ECGF).

A two-site enzyme immunoassay for gliostatin (GLS)/platelet-derived endothelial cell growth factor (PD-ECGF) has been developed. The detection limit of gliostatin/PD-ECGF was 30 pg/well, and the optimal assay range was 0.1 to ng/well. This assay system enabled us to confirm the immunochemical identity of both factors and to detect immunoreactive gliostatin/PD-ECGF (IR-GLS/PD-ECGF) in human biological body fluids. The age-related analysis from newborn to 69 years revealed that the serum IR-GLS/PD-ECGF level was high in infants younger than 1 year old (1.8 ng/ml) and in the 20-year-old age group (1.8 ng/ml), and highest in the umbilical cord blood (2.1 ng/ml). Curiously high concentrations were detected in saliva with a significant sex difference (11.3 ng/ml for males and 48.7 ng/ml for females), and in synovial fluids (3.7 ng/ml). A number of human tumor cells, gastric cancer cells, MKN-74, neuroblastoma cells, GOTO, as well as epidermoid carcinoma cells, A431, were found to produce a significant amount of IR-GLS/PD-ECGF (0.2 to 21.8 ng/mg protein), and some of them secreted the IR-GLS/PD-ECGF in the conditioned medium (approximately 0.5 ng/ml). The enzyme immunoassay system is sufficiently sensitive for the basic and clinical study of gliostatin/PD-ECGF in human body fluids, tissues and organs.

Attenuation of the reflex responses to muscle contraction by the coadministration of antagonists to substance P and somatostatin into the dorsal horn.

OBJECTIVE: The aim was to determine if the coadministration of antagonists to substance P and somatostatin into the L7 dorsal horn blunts the reflex cardiovascular responses to static contraction to a greater extent than each antagonist alone. The possibility that this attenuation is mediated by blunting the contraction evoked increases in sympathetic outflow was also tested. METHODS: Using alpha chloralose anaesthetised cats (n = 8), static contraction and stretch of the triceps surae muscle were performed before and after microinjecting (1 microliter) 250 ng of the substance P antagonist, D-Pro2-D-Phe7-D-Trp9-substance P, and the somatostatin antagonist, cyclo(7-amino-heptanoyl-phenylalanyl-D-tryptophyl-lysyl-threonyl-[ benzyl]). The muscle was contracted by electrically stimulating the peripheral end of the cut L7 ventral root. RESULTS: Before injecting the antagonists, static muscle contraction increased mean arterial blood pressure by 40(SEM 6) mm Hg, heart rate by 13(2) beats.min-1, and renal sympathetic nerve activity (RSNA) by 41(7)%. These changes were blunted by the antagonists since the increases in blood pressure, heart rate, and RSNA were reduced to 21(3) mm Hg, 8(1) beats.min-1, and 23(5)%, respectively. In contrast, antagonist administration did not affect the pressor [33(5) v 31(5) mm Hg], heart rate [9(2) v 10(2) beats.min-1], or RSNA [23(4)% v 25(5)%] responses to muscle stretch. Microinjection of 2% lignocaine into the dorsal horn virtually abolished the reflex changes elicited by muscle stretch. CONCLUSIONS: The release of substance P and somatostatin in the spinal cord plays a role in mediating the cardiovascular changes caused by static contraction, but the release of other neurotransmitters/neuromodulators is also involved. The attenuation produced by these antagonists is mediated, at least in part, by reducing sympathetic outflow.

Protective effects of alpha-tocopherol and coenzyme Q10 on warm ischemic damages of the rat kidney.

Studies were done on the protective effects of alpha-tocopherol and coenzyme Q10 (CoQ10) on warm ischemic damage to the rat kidney. Administration of alpha-tocopherol (10 mg/kg body wt/day) for 7 days or a single i.p. injection of CoQ10 (6 mg/kg body wt) increased the survival rate from 0 to 46.7% of the rats subjected to warm ischemia for 120 min. The administration of alpha-tocopherol and CoQ10 increased adenosine triphosphate (ATP) in the renal tissue from 0.53 +/- 0.18 to 0.92 +/- 0.29, and from 0.64 +/- 0.26 to 1.00 +/- 0.54 mumol/g wet weight, respectively, 4-hr reperfusion after 120 min of warm ischemia. Serum creatinine levels of the surviving rats after 120 min of warm ischemia was 9.98 +/- 0.19 mg/100 ml in the control group and 5.84 +/- 0.95 and 7.27 +/- 1.62 mg/100 ml, respectively, in alpha-tocopherol and CoQ10 administered group, when determined 2 days after the operation. These results indicate that alpha-tocopherol and CoQ10 have a protective effect on warm ischemic damage to the rat kidney, demonstrated by an increase in ATP resynthesis after reflow following warm ischemia and by the maintenance of a lower serum creatinine level. This effect was accompanied by an increase in the survival rate of ischemic rats.

Cardiovascular responses during spontaneous overground locomotion in freely moving decerebrate cats.

To examine whether the cerebrum is essential for producing the rapid cardiovascular adjustment at the beginning of overground locomotion, we examined heart rate (HR), mean arterial blood pressure (MAP), and integrated electromyogram (iEMG) of the forelimb triceps brachialis muscle in freely moving decerebrate cats during locomotion. Two to four days after decerebration surgery performed at the level of the precollicular-premammillary body, the animals spontaneously produced coordinated overground locomotion, supporting body weight. HR began to increase immediately before the onset of iEMG, and MAP began to rise almost simultaneously with the iEMG onset. Their increases in HR and MAP (24 +/- 3 beats/min and 22 +/- 4 mmHg) were sustained during locomotion. Sinoaortic denervation (SAD) did not affect the abrupt changes in HR and MAP at the beginning of locomotion (0-4 s from the onset of iEMG), whereas SAD had a contrasting effect during the subsequent period, a decrease in the HR response (9 +/- 1 beats/min) and an increase in the MAP response (30 +/- 3 mmHg). These results suggest that the cerebrum and the rostral part of the diencephalon are not essential for producing the rapid cardiovascular adjustment at the beginning of spontaneous overground locomotion. The arterial baroreflex does not contribute to this rapid adjustment but plays an important role in regulating the cardiovascular responses during the later period of spontaneous locomotion.

Responses of cerebellar Purkinje cells to mechanical perturbations during locomotion of decerebrate cats.

During the locomotion of cats which had been decerebrated at the precollicular and premammillary level, mechanical perturbations (taps of 50-550 g wt.) were applied to the paw dorsum of the left forelimb. Purkinje cells were recorded from the vermis of the cerebellar anterior lobe, and those connected to Deiters' neurons controlling the right forelimb were identified by antidromic and orthodromic stimuli. Taps on the left forelimb induced in these Purkinje cells two types of responses; I-type is a depression of simple spike discharge, often preceded by a brief phase of facilitation, and E-type is entirely a facilitation of simple spike discharge. Complex spikes, representing activation through climbing fiber afferents, were frequently evoked by the taps in both I- and E-types. The I-type depression in Purkinje cells closely corresponds to the previously reported facilitation in Deiters' neurons and forelimb extensor muscles, suggesting that the interlimb coordination during cat's locomotion is effected by linked activity of vermal Purkinje cells and Deiters' neurons.

Multiplicity of the afferent pathways mediating the exercise pressor reflex.

The cardiovascular responses to isometric contraction of the triceps surae muscle of one leg were determined before and after transecting the ipsilateral L7 or L6 and S1 spinal roots. Sectioning only the L7 spinal root slightly attenuated the pressor, but not the heart rate response induced by skeletal muscle contraction, while cutting the L6 and S1 spinal roots (L7 intact) had no effect on the cardiovascular changes. This indicates that there is multiplicity in neural afferent pathways that mediate the exercise pressor reflex.

High concentrations of immunoreactive gliostatin/platelet-derived endothelial cell growth factor in synovial fluid and serum of rheumatoid arthritis.

Since neovascularization plays an important role in the propagation of rheumatoid synovitis, we analyzed the concentration of gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF), a potent angiogenic and chemotactic factor, in the synovial fluid and serum of rheumatoid arthritis (RA) patients. The immunoreactive GLS/PD-ECGF concentrations (mean value +/- S.D.) in synovial fluid, measured by a sandwich enzyme immunoassay, were significantly higher in RA patients than in osteoarthritis (OA) patients (233.02 +/- 219.40 vs. 9.09 +/- 14.86 ng/g, P < 0.001), and the serum concentrations were also higher in RA patients than in age-matched controls (8.77 +/- 7.60 vs. 3.74 +/- 2.61 ng/ml, P < 0.005). These results suggest that GLS/PD-ECGF may participate in the endothelial proliferation resulting in initiation of the extensive emigration of mononuclear cells and proliferation of the synovial tissues in rheumatoid arthritis, and that the immunoreactive GLS/PD-ECGF in serum as well as synovial fluids may be a useful diagnostic marker of RA.

Interlaboratory validation of the in vitro eye irritation tests for cosmetic ingredients. (11) EYTEX(TM).

EYTEX(TM) is an in vitro test system for predicting the ocular irritation potential of chemicals and formulations. This method was evaluated as an alternative method to the Draize eye irritation test (Draize test) for the eye irritation potential of several cosmetic ingredients in a three-phase validation study conducted at five to seven laboratories. Thirty-nine test substances were used as coded samples. The test procedures were controlled under the same standard operating procedure (SOP) at all participating laboratories. The interlaboratory coefficient of variation (CV) was 20.8%. The correlation coefficient between EYTEX scores and the maximal average Draize total score (MAS) was 0.313. Irritancy classifications were established based on the results of 54 EYTEX tests and the EYTEX/Draize equivalent was calculated. Thirty-eight EYTEX test results concurred with the results of the Draize test, substantial equivalence was 70.4%. These results indicate that EYTEX provides a rough method of classification rather than providing absolute values. The present results also indicate that EYTEX has the following characteristics: (1) intensely coloured substance may not be compatible; (2) some cationic surfactants may be underestimated; (3) EYTEX can be applied to most test substances under the same conditions as the in vivo tests.

Interlaboratory Validation of the in vitro Eye Irritation Tests for Cosmetic Ingredients. (4) Haemoglobin Denaturation Test.

Interlaboratory validation of the haemoglobin denaturation (HD) test on 38 cosmetic ingredients was conducted by five to eight participating laboratories. The HD test was evaluated as an alternative method to the Draize eye irritation test (Draize test) based on three indices of protein denaturation: the test substance concentration that induces 50% HD of the positive control (RDC(50)), a relative HD rate at 1% of the test substance (1%RDR) and a relative change in maximum absorption wavelength (1% lambdamax). The coefficients of variation associated with a positive HD test among the participating laboratories were within an acceptable range for practical application. The in vitro test results were in relatively good agreement with the Draize test. The correlation coefficient (r) between the in vivo maximal average Draize total score (MAS) and log (RDC(50)), 1%RDR and 1% lambdamax were -0.91, 0.67 and 0.79, respectively. The results revealed several limitations associated with the HD test: (1) the HD test cannot be applied to coloured test substances with a strong absorption, around 418nm; (2) water-insoluble test substances cannot be evaluated by RDC(50) or 1%RDR; (3) the HD test cannot be applied to strong acids that exceed the buffering capacity of a phosphate buffer solution; (4) the HD test cannot be used to determine the potential for eye irritation caused by factors other than protein denaturation, for example, polyoxyethylene octylphenylether (10 E.O.). Thus, the HD test alone is not appropriate for predicting eye irritation potential. Nevertheless, the good agreement between the HD test results and in vivo irritation scores as well as the ease of application suggest that this test may play an important role in a test system to determine eye irritation potential.

Interlaboratory validation of the in vitro eye irritation tests for cosmetic ingredients. (1) Overview of the validation study and Draize scores for the evaluation of the tests.

A three-step interlaboratory validation of alternative methods to the Draize eye irritation test (Draize test) was conducted by the co-operation of 27 organizations including national research institutes, universities, cosmetic industries, kit suppliers and others. Twelve alternative methods were evaluated using 38 cosmetic ingredients and isotonic sodium chloride solution. Draize tests were conducted according to the OECD guidelines using the same lot of test substances as was evaluated in the alternative tests. Results were as follows. (1) Variation in Draize scores was large near the critical range (maximal average Draize total scores (MAS)=15-50) for the evaluation of cosmetic ingredients. (2) Interlaboratory variation was relatively small for the alternative tests. The mean coefficients of variation (CV%) were less than 50 for all assays except for the hen's egg-chorioallantoic membrane test (HET-CAM), chorioallantoic membrane-trypan blue staining test (CAM-TB) and haemoglobin denaturation test (HD). The CV% of these three methods came into the same range as the other tests when non-irritants were excluded from the data analysis. (3) Results for acids (pH of 10% solution <2.5), alkalis (pH of 10% solution >11.5) and alcohols (lower mono-ol) in cytotoxicity tests clearly deviated from the other samples in the comparison of cytotoxicity with Draize results. (4) Pearson's correlation coefficients (r) between results from cytotoxicity tests using serum and MAS were -0.86 to -0.92 for samples excluding acids, alkalis and alcohols. (5) When the samples were divided into liquids and powders, r of CAM-TB increased from 0.71 for all samples to 0.80 and 0.92, respectively. (6) Spearman's rank correlation coefficients between the results of alternative methods and MAS were relatively high (r>0.8) in the case of HET-CAM and CAM-TB. Those for cytotoxicity tests were high if the data for acids, alkalis and alcohols were excluded (SIRC-CVS: r=0.945, SIRC-NRU: r=0.931, HeLa-MTT: r=0.926, CHL-CVS: r=0.880). Exclusion of data for powdered samples also increased the coefficient of HET-CAM and CAM-TB to 0.831 and 0.863, respectively. These results suggest that no single method can constitute an evaluation system applicable to all types of test substances by itself. However, several methods will be useful for the prediction of eye irritation potential of cosmetic ingredients if they are used with clear understanding of the characteristics of those methods.

Transient responses of heart rate, arterial pressure, and head movement at the beginning of eating in awake cats.

Time courses of heart rate (HR), arterial pressure (AP), and head movement at the beginning of eating were analyzed in conscious cats. The cats were trained to eat when movements of their body trunks were restrained. Food was presented for 10 sec at intervals of 100 sec. With the abrupt presentation of food, a head-down movement occurred immediately and thereafter eating started with a mean latency of 1.6 sec. During eating HR increased by 22% from the preeating value and AP was elevated by 11%. To determine the time relation between the onset of eating and the change in each variable in response to eating, mean time courses of HR, AP, and head movement were obtained from 7-40 trials in each cat. The head-down movement preceded the onset of eating by 1.3 sec. The increase in HR preceded the onset of eating by 0.2 sec; the change in AP followed it by 3-4 sec. This indicated that the increase in HR was not induced reflexly either by food intake or by the change in AP. After administration of hexamethonium, the changes in HR and AP in response to eating were abolished, although eating was evoked by the food presentation. Additionally, the increase in HR was also reduced by propranolol and atropine. Thus, the acceleration of HR at the beginning of eating may be induced by central activation of the autonomic nervous system.

Nitric oxide mediates cat hindlimb cholinergic vasodilation induced by stimulation of posterior hypothalamus.

The aim of this work was to examine whether endothelium-derived relaxing factor (nitric oxide) mediates cat hindlimb cholinergic vasodilation induced by stimulation of the posterior hypothalamus and beta-adrenergic vasodilation by I.V. injection of isoproterenol using an inhibitor of nitric oxide synthesis, NW-nitro-L-arginine methyl ester (L-NAME). Without L-NAME, femoral blood flow velocity (FBV) increased during hypothalamic stimulation by 11.2 +/- 2.2 cm/s (mean +/- SEM) from the baseline value of 8.4 +/- 2.2 cm/s and femoral conductance (FC) increased by 0.084 +/- 0.021 cm/s/mmHg from 0.062 +/- 0.016 cm/s/mmHg, which were abolished by atropine (0.5 mg I.A.). Arterial blood pressure (AP) and heart rate (HR) increased during hypothalamic stimulation (15 +/- 8 mmHg and 22 +/- 6 beats/min). When isoproterenol (1-2 micrograms I.V.) was injected, FBV and FC increased 5.1 +/- 0.56 cm/s and 0.048 +/- 0.005 cm/s/mmHg. With L-NAME (20-100 mg I.A.), the rises in AP and HR during hypothalamic stimulation were unchanged but the increases in FBV and FC were significantly blunted to 5.2 +/- 3.7 cm/s and 0.026 +/- 0.021 cm/s/mmHg. In contrast, L-NAME did not affect the responses in FBV and FC during stimulation of beta-adrenergic receptors. The effect of NG-monomethyl-L-arginine (10-30 mg I.A.) was the same as L-NAME. It is suggested that nitric oxide is involved in hindlimb cholinergic vasodilation neurally induced by hypothalamic stimulation but not in beta-adrenergic vasodilation.

Fundamental rhythm of cardiac sympathetic nerve activity in awake cats at rest and during body movement.

Cardiac sympathetic nerve activity (CSNA in imp/s) was measured in the postganglionic fibers of awake cats at rest, during body movement, and with excitement. The CSNA showed synchronized discharges with various periodicities. Rhythms of the synchronized CSNA were analyzed by an interval histogram (IIH). The IIH showed a multimodal distribution. The first model interval (Tc) was in a range of 75 to 125 ms. An 8-12 cycle/s Tc rhythm, i.e., inverse value of Tc, was always observed in the awake cat at rest and during body movements. Probability of the 8-12 cycle/s Tc rhythm was smallest at rest, increased during body movement, and was largest with excitement. These results suggested that the 8-12 cycle/s Tc rhythm, observed in all states in the conscious cat, is a fundamental rhythm of central cardiovasomotor origin. The subsequent model distribution (Tb = 2 x Tc, 3 x Tc, 4 x Tc, or 5 x Tc) ranged from 150 to 700 ms, mostly 200 to 500 ms. A 2-5 cycle/s Tb rhythm, i.e., inverse value of Tb, appeared more frequently at rest than that during body movement or with excitement. A new model concerning a mechanism to cause the 2-5 cycle/s Tb rhythm is suggested.

Effect of renal denervation on the compensatory renal growth following nephrectomy in the cat.

The purpose of this study was to clarify the effect of denervation on the mass of the remaining kidney with or without unilateral nephrectomy using adult cats. The animals were divided into 4 groups: (1) control group, the weights of the right and left kidneys were measured intact in 5 cats; (2) nephrectomy group (Nx, n = 5 cats), the right kidney was removed and the left kidney was weighed 3-5 d after nephrectomy; (3) nephrectomy and denervation group (Nx+Dx, n = 7 cats), the left kidney was weighed on the 7th day after surgery in which the left kidney was denervated and the right kidney was removed; and (4) denervation group (Dx+Dx, n = 5 cats), both kidneys were weighed on the 7th day after denervation of the kidneys. In the control group, the left and right kidney weights per body weight (LKW and RKW) were the same (LKW, 0.74 +/- 0.06%; RKW, 0. 74 +/- 0.07%). In the Nx group, LKW increased to 0.90 +/- 0.03% 3-5 d after nephrectomy, although RKW of the removed kidney was 0.66 +/- 0.01%. In the Nx+Dx group, LKW increased to 0.97 +/- 0.15%, which was similar to that of the Nx group. In the Dx+Dx group, LKW (0.56 +/- 0.05%) and RKW (0.54 +/- 0.05%) were significantly less than those in the control group. We conclude that the renal nerves may contribute to maintaining the renal mass and that the neural effect on compensatory growth following nephrectomy may be covered by other growth factors.

Effects of baroceptor reflex on cardiac and renal sympathetic nerve activity before and after atropinization in awake cats at rest.

The effects of baroceptor reflex on mean cardiac (MCSNA) and renal sympathetic nerve activity (MRNA) were analyzed before and after atropinized (0.1 mg/kg, i.v.) states in conscious cats at rest. Resting values of MCSNA, MRNA, mean aortic pressure (MAP), and heart rate (HR) were 85 +/- 6 imps/s, 76 +/- 11 imps/s, 100 +/- 4 mmHg, and 164 +/- 10 beats/min, respectively. Both MCSNA and MRNA changed almost inversely to changes in the absolute MAP in the range of 90-140 mmHg. Within this pressure range the gain of baroceptor-sympathetic system to the heart and kidney was 2.31 and 1.84, respectively. MCSNA as well as MRNA was reduced to the noise level at the MAP of 142 and 150 mmHg, respectively. With atropine, MCSNA and MRNA were inhibited centrally whereas HR increased to 192 beats/min. The increase in MAP caused by norepinephrine (2.1 micrograms/kg, i.v.) was enhanced to 75 +/- 7 mmHg by atropine from 31 +/- 4 mmHg in control. The piecewise linear MAP-MCSNA and MAP-MRNA relationships changed to a remarkable clockwise hysteresis loop. During the rising MAP period, the gain of the baroceptor-sympathetic system decreased to 0.91 and 0.97 in MCSNA and MRNA, respectively. During the returning MAP period, a delayed activation in MCSNA and MRNA occurred centrally. We conclude that the baroceptor reflex effect on MCSNA is larger than those on MRNA, and that the baroceptor control of MCSNA and MRNA is modified centrally by atropine in the awake cat at rest.

Reflex responses in plasma catecholamines caused by static contraction of skeletal muscle.

To examine a hypothesis of whether static muscle contraction produces a release of catecholamines from the adrenal medulla via reflex stimulation of preganglionic adrenal sympathetic nerve activity induced by receptors in the contracting muscle, we compared the reflex responses in a concentration of epinephrine (Ep) and norepinephrine (NEp) in arterial plasma during static contraction and during a mechanical stretch of the hindlimb triceps surae muscle in anesthetized cats. Static contraction was evoked by electrically stimulating the peripheral ends of the cut L(7) and S(1) ventral roots at 20 or 40 Hz. Mean arterial pressure (MAP) and heart rate (HR) increased 23 +/- 3.1 mmHg and 19 +/- 4.3 beats/min during static contraction. Ep in arterial plasma increased 0.18 +/- 0.072 ng/ml over the control of 0.14 +/- 0.051 ng/ml within 1 min from the onset of static contraction, and NEp increased 0.47 +/- 0.087 ng/ml over the control of 0.71 +/- 0.108 ng/ml. Following a neuromuscular blockade, although the same ventral root stimulation failed to produce the cardiovascular and plasma catecholamine responses, the mechanical stretch of the muscle increased MAP, HR, and plasma Ep, but not plasma NEp. With bilateral adrenalectomy, the baseline Ep became negligible (0.012 +/- 0.001 ng/ml) and the baseline NEp was lowered to 0.52 +/- 0.109 ng/ml. Neither static contraction nor mechanical stretch produced significant responses in plasma Ep and NEp following the adrenalectomy. These results suggest that static muscle contraction augments preganglionic adrenal sympathetic nerve activity, which in turn secretes epinephrine from the adrenal medulla into plasma. A muscle mechanoreflex from the contracting muscle may play a role in stimulation of the adrenal sympathetic nerve activity.

Noninvasive evaluation of cardiac output during postural change and exercise in humans: comparison between the modelflow and pulse dye-densitometry.

To investigate whether the Model-flow method, by simulating the aortic input impedance model from a noninvasive monitoring of arterial blood pressure, reflected a reliable measure of cardiac output (CO) during postural change and whole-body exercise occurring in daily life, we compared the Modelflow-estimated CO with a simultaneous reference determined by the pulse dye-densitometry. Nine healthy volunteers performed postural change from supine to upright and dynamic stepping exercise. The Modelflow-estimated CO decreased to 4.8 +/- 0.5 l/min, from 5.8 +/- 0.6 l/min, during the postural change and increased to 12.8 +/- 1.3 l/min during a stepping exercise, returning to 5.1 +/- 0.4 l/min at 5 min after exercise. When comparing the pooled data of CO during resting and following exercise between the Modelflow and pulse dye-densitometry, we found that the average CO did not differ between the two estimates and that there was a significant correlation between them; the slope of the linear regression line corresponded to approximately 1.0. Although such linear relationship was also observed in an individual subject, the slope of the regression line varied from 0.737 to 1.588 among the subjects. The calibration of the Modelflow-estimated CO with the dye-densitometry value at supine or upright improved a correlation between the two estimates. Thus it is likely that the noninvasive Modelflow simulation from arterial blood pressure can provide a reliable estimation of group-average cardiac output during postural change and stepping exercise occurring in daily life. It will be recommended for a more accurate estimation of cardiac output in a given subject to calibrate the Modelflow data with an independent measure.