Biomedical subjects

H I Chen

Publications and source records attributed to H I Chen.

At least 19 recordsLinked to original sources

PubMed1995

The WW domain of Yes-associated protein binds a proline-rich ligand that differs from the consensus established for Src homology 3-binding modules.

The WW domain has previously been described as a motif of 38 semiconserved residues found in seemingly unrelated proteins, such as dystrophin, Yes-associated protein (YAP), and two transcriptional regulators, Rsp-5 and FE65. The molecular function of the WW domain has been unknown until this time. Using a functional screen of a cDNA expression library, we have identified two putative ligands of the WW domain of YAP, which we named WBP-1 and WBP-2. Peptide sequence comparison between the two partial clones revealed a homologous region consisting of a proline-rich domain followed by a tyrosine residue (with the shared sequence PPPPY), which we shall call the PY motif. Binding assays and site-specific mutagenesis have shown that the PY motif binds with relatively high affinity and specificity to the WW domain of YAP, with the preliminary consensus XPPXY being critical for binding. Herein, we have implicated the WW domain with a role in mediating protein-protein interactions, as a variant of the paradigm set by Src homology 3 domains and their proline-rich ligands.

Adaptor Proteins, Signal Transducing↗

PubMed1995

Characterization of a novel protein-binding module--the WW domain.

We have identified, characterized and cloned human, mouse and chicken cDNA of a novel protein that binds to the Src homology domain 3 (SH3) of the Yes proto-oncogene product. We subsequently named it YAP for Yes-associated protein. Analysis of the YAP sequence revealed a protein module that was found in various structural, regulatory and signaling molecules. Because one of the prominent features of this sequence motif is the presence of two conserved tryptophans (W), we named it the WW domain. Using a functional screen of a cDNA expression library, we have identified two putative ligands of the WW domain of YAP which we named WBP-1 and WBP-2. Peptide sequence comparison between the two partial clones revealed a homologous proline-rich region. Binding assays and site-specific mutagenesis have shown that the proline-rich motif binds with relatively high affinity and specificity to the WW domain of YAP, with a preliminary consensus that is different from the SH3-binding PXXP motif. This suggests that the WW domain has a role in mediating protein-protein interactions via proline-rich regions, similar but distinct from Src homology 3 (SH3) domains. Based on this finding, we hypothesize that additional protein modules exist and that they could be isolated using proline-rich peptides as functional probes.

Adaptor Proteins, Signal Transducing↗

PubMed1995

Measurement of nitric oxide release in the isolated perfused rat lung.

In this study we have continuously measured real-time production of nitric oxide (NO) in the isolated, perfused rat lung by using an NO monitor (model NO-501, Inter Medical Co., Nagoya, Japan) with an NO-selective resin microsensor. A stable NO response was obtained when the sensor was placed in the pulmonary artery or the pulmonary vein; in contrast, the tracings obtained from the lung periphery were unstable. Furthermore, the NO release was higher when the isolated lungs were perfused with physiological salt solution rather than whole blood perfusion. Changes in NO production were also monitored in acute hypoxia and reoxygenation. Pretreatment with endotoxin (10 mg/kg) potentiated the NO release observed, and this effect of endotoxin was further potentiated by arginine (1 x 10(-4) M) and acetylcholine (1 x 10(-5) M) and countered by the NO synthase inhibitor, L-NG-nitro-arginine methyl ester (L-NAME; 1 x 10(-3) M).

Animals↗

PubMed1995

Effects of exercise training and deconditioning on platelet function in men.

Platelets play an important role in the pathogenesis of cardiovascular disease. It has also been noticed that regular exercise can reduce the risk of cardiovascular disease. This is the first study to demonstrate that endurance exercise training may suppress platelet adhesiveness and aggregation and that deconditioning may reverse the training effects. Healthy male sedentary subjects were randomly divided into control and training groups. The trained men were trained on a bicycle ergometer at about 60% of maximal oxygen consumption for 30 minutes per day, 5 days per week for 8 weeks, then deconditioned for 12 weeks. During the experimental period, blood samples of the trained subjects were collected before and immediately after a progressive exercise test every 4 weeks. The same experiments were applied to the controls at the beginning of this study and 8 weeks thereafter. A tapered parallel-plate chamber was used to assess platelet adhesiveness. Platelet aggregation induced by ADP was evaluated by the percentage of reduction in single platelet count. Our results showed that (1) platelet adhesiveness and aggregability were increased by short-term strenuous exercise in both control and trained groups, but the enhancement of platelet aggregability was decreased after exercise training in the trained subjects; (2) at rest and immediately after strenuous exercise, platelet adhesiveness and aggregability were decreased by training, whereas they were unchanged in the control group; and (3) deconditioning reversed the training effects on resting and postexercise platelet adhesiveness and aggregability back to the pretraining state. These results suggest that platelet adhesiveness and aggregability may be depressed by exercise training but be reversed back to the pretraining state after deconditioning.

Blood Platelets↗

PubMed1995

Immunomodulatory effects of acute exercise bout in sedentary and trained rats.

The immune response to acute exercise after long-term training was evaluated in rats. After 10 wk of exercise training on a drum exerciser, both sedentary control and trained groups ran with the intensity of 70% of peak oxygen consumption (VO2peak) for 10 min immediately before sacrifice. The mitogenic activity of spleen lymphocytes in trained group to staphylococcal enterotoxin B, a polyclonal T cell activator, decreased as compared to the sedentary control following acute exercise. However, proliferative response to lipopolysaccharide, a B cell mitogen, was augmented. Furthermore, the interleukin-2 production was reduced in the trained group. The lymphocyte subpopulations in the spleen and the peripheral blood lymphocytes were analyzed by flow cytometry. Although the tendency of changes in some populations was observed in trained vs untrained groups, no statistically significant difference was manifested. The serum levels of both norepinephrine and epinephrine increased immediately after acute exercise. The increase in serum lactate concentration was observed following acute exercise in sedentary control, but less prominent in the trained group.

Animals↗

PubMed1994

Origins of sympathetic innervation to the mesenteric vein vessel in cats.

Physiological and histochemical studies have clearly demonstrated the control and innervation of the sympathetic nerve on the splanchnic veins. However, the origins of postganglionic fibers remain to be determined. In this study, we used the retrograde transport of horseradish peroxidase (HRP) technique to trace the origins of postganglionic neurons in pre- and paravertebral sympathetic ganglia that innervate the mesenteric vein. A segment (6-8 mm) of mesenteric vein close to the duodeno-jejunal junction was isolated. HRP was applied externally on the vein segment to allow uptake into the nerve endings. In 10 cats, there was a total of 9275 HRP-labeled neurons in the pre- and paravertebral ganglia. The neuron distribution (mean +/- S.E.M.) was as follows: 452 +/- 77 (49%) in the superior mesenteric ganglion (SMG), 248 +/- 62 (27%) in the right celiac ganglion (RCG), 111 +/- 23 (12%) in the left celiac ganglion (LCG) and 58 +/- 16 (6%) in the splanchnic ganglia. Although the appearance of HRP neurons in the paravertebral ganglia (T10-L3) was relatively sparse, there were still significant numbers in L1 (26 +/- 13, 3%), T13 (15 +/- 5, 2%) and other ganglia. The results indicate that more than 90% of the presynaptic sympathetic neurons innervating the mesenteric vein make their synaptic connections in the prevertebral ganglia, mostly SMG and then RCG as well as LCG. Postsynaptic neurons arising directly from the paravertebral ganglia (mostly L1 and T13) constitute to about 6% of the total.

Animals↗

PubMed1994

The correlation of cardiac mass with arterial haemodynamics of resistive and capacitive load in rats with normotension and established hypertension.

In hypertensive animals and humans, cardiac hypertrophy may occur as a consequence of an external load on the heart. Several studies have suggested that the non-pulsatile components of arterial haemodynamics, such as arterial pressure and vascular resistance, do not adequately represent the ventricular afterload and are not well correlated with the degree of cardiac hypertrophy (CH). The present study was undertaken to analyse the correlation between the degree of CH and various haemodynamic parameters in the spontaneously hypertensive rat (SHR) with established hypertension. A total of 36 SHRs (6-8 months) with a tail-cuff pressure above 190 mm Hg were used. Control data were obtained from 32 age-matched normotensive Wistar Kyoto rats (WKY). Animals were anaesthetized with pentobarbitone sodium (40 mg/kg i.p.) and artificially ventilated with a respirator. A Millar catheter with a high-fidelity pressure sensor was used to record the aortic pressure and an electromagnetic flow transducer to monitor the aortic flow. The pressure and flow signals were subjected to Fourier transformation for the analysis of the arterial impedance spectrum. The left ventricular weight-to-body weight ratio (LVW/BW) was taken as a measure of the degree of CH. The measured haemodynamic parameters in these anaesthetized, open-chest SHRs were systolic pressure (SP) (mean +/- SE) 172 +/- 4 mm Hg, diastolic pressure (DP), 120 +/- 3 mm Hg, pulse pressure (PP) 52 +/- 2 mm Hg, peripheral resistance (Rp) 344,032 +/- 8,012 dyne.s.cm-5, characteristic impedance (Zc) 6,442 +/- 313 dyne.s.cm-5, the impedance modulus at the first harmonic (Z1) 26,611 +/- 1,061 dyne.s.cm-5, mean arterial compliance (Cm) 0.87 +/- 0.04 microliter/mm Hg and LVW/BW 3.092 +/- 0.026 mg/g.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Regional differences in prostaglandin production rates among porcine intrathoracic vessels.

To investigate the regional variability in intrathoracic vascular prostaglandin (PG) synthesis, we obtained vessel segments from porcine coronary artery (COA), thoracic aorta (AT), common carotid artery (CRA), pulmonary artery (PA), pulmonary vein (PV), and inferior vena cava (IVC). Vascular production rates of 6-keto-PGF1 alpha (an indicator for PGI2), PGF2 alpha, and PGE2 were measured both in unstimulated state and in arachidonic acid-stimulated state using immunosorbent assays. Our results indicated that PGI2 production rate in all vessel segments decayed with time after vessel dissection. In all vessel segments tested under unstimulated conditions, PGI2 production rates were about one order of magnitude higher than PGF2 alpha and PGE2 production rates of the same specimens. Results from unstimulated, 1.5 hr pre-incubated specimens indicated that i) PGI2 production rates in COA, AT, and PV were greater than those in CRA, PA, and IVC; ii) PGF2 alpha production rates from the same specimens were higher in PV than in AT, CRA, and IVC, while these in PA were higher than in IVC; and iii) PGE2 production rates from the same specimens were not significantly different from one another. Arachidonic acid added at about 1.5 hr after vessel harvest stimulated the PGI2 and PGF2 alpha synthesis rates by 3 to 15 folds. However, this arachidonic acid treatment caused 70 to 300-fold increases in PGE2 production rates, reaching levels comparable to PGI2. All three prostanoid production rates under stimulated conditions were also variable among different intrathoracic vessels. Although either physiological gas concentrations or local hemodynamic conditions alone can partially explain our results, which physiological parameter(s) actually causes these regional differences remains to be verified.

Animals↗

PubMed1994

The sympathetic efferent innervation of the cutaneous and muscle veins in cats. A comparative study using retrograde localization with horseradish peroxidase.

Previous studies using electrical stimulation, tension recording and fluorescence histochemical methods indicate that variations in the sympathoadrenergic innervation exist in regional veins of the limb. In the present experiment, we used horseradish peroxidase (HRP) as a retrograde tracer to localize and quantitate the sympathetic innervations to the saphenous, femoral and muscle veins in the cat. The animal was anesthetized with pentobarbital. In three groups of cats, a segment of saphenous (n = 8), femoral (n = 8) and muscle (n = 10) vein was isolated. HRP was applied on the outer vein wall for 3-4 h to allow uptake into the nerve endings. The paravertebral sympathetic chain on the same side of HRP application was dissected after the animal was killed and fixed 60 h following the application of tracer. HRP-labeled neurons were counted in each sympathetic ganglion from L1 to S1. The average number of neurons (mean +/- SE) were 913 +/- 99, 732 +/- 70 and 234 +/- 32, respectively, for saphenous, femoral and muscle vein. There was no statistical difference between the saphenous and femoral vein (P > 0.1). The muscle vein was far less innervated (P < 0.001). When the surface area (mm2) of the vein segment for HRP application was taken into account, the neurons per mm2 were 44.1 +/- 4.8 for saphenous vein, 24.6 +/- 1.8 for femoral vein and 10.2 +/- 1.3 for muscle vein. The neuron density was significantly different among the three groups (P < 0.01). In a single ganglion, the distribution of HRP-neurons appeared to be scattering in pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Exponentially tapered t-tube model of systemic arterial system in dogs.

This study determines the role of an asymmetric T-tube model as a representation of arterial mechanical properties. The model consists of two non-uniform tubes connected in parallel. The non-uniform properties of each tube include geometric and elastic tapering and each tube terminates in a complex load. Pulsatile pressure and flow velocity of the ascending aorta were measured in 10 closed-chest, anaesthetized dogs. An exponentially tapered transmission line is used to describe the non-uniform properties of the vasculature. The phase constant is a function of position along the path length due to geometric and elastic tapers. This non-uniform T-tube model makes it possible to fit the measured pressure waveform in the ascending aorta. Model parameters could be estimated and used to interpret the physical properties of the arterial system. The mathematical and experimental model impedance spectra are similar. There is a close correspondence between the impedance parameters derived from the non-uniform T-tube model and values computed from measurements on dogs. The results suggest that inclusion of tube tapering improves the mathematical model so that it closely represents the experimentally derived arterial impedance in closed-chest dogs. We conclude that the non-uniform properties of wave-transmission paths may play an important role in governing the behaviour of an asymmetric T-tube for the description of the arterial system.

Animals↗

PubMed1994

Impaired left ventricular relaxation and arterial stiffness in patients with essential hypertension.

1. This study was designed to determine how left ventricular relaxation function in patients with essential hypertension is impaired by arterial haemodynamic load that is increased in early ejection phase. These patients did not suffer from cardiac hypertrophy or disturbed coronary perfusion. We used a high-fidelity multisensor catheter to record pressure and flow signals in the ascending aorta. The timing and magnitude of wave reflection were obtained by decomposing the measured waves into their forward and backward components. Radionuclide angiography was employed to obtain the time-activity curve. The left ventricular relaxation function was assessed by analysing the time-activity curve, which was filtered using Fourier expansion with the number of harmonics for minimum error. 2. In comparison with age-matched normotensive subjects (seven subjects with mean blood pressure 97 mmHg), hypertensive subjects (seven subjects with mean blood pressure 138 mmHg) had a shorter backward wave arrival time (193 +/- 26 versus 258 +/- 35 ms) and a higher reflection factor (0.58 +/- 0.12 versus 0.42 +/- 0.07). Isovolumic relaxation period was prolonged in hypertensive subjects (118 +/- 19 versus 90 +/- 19 ms). There was an inverse correlation between isovolumic relaxation period and backward wave arrival time in all 14 subjects (r = -0.67, P < 0.05). In contrast, there were no significant differences in cardiac output and time to peak ejection rate between the two groups. 3. Our analyses revealed that early return of the enhanced wave reflection may profoundly impair left ventricular relaxation function in patients with hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗

PubMed1994

Ischemia-reperfusion lung injury attenuated by ATP-MgCl2 in rats.

The protective effect of ATP-MgCl2 on ischemia-reperfusion lung injury has been reported in kidney, liver, heart, and muscle but has not been examined in lungs. The aim of this study was to determine whether ATP or ATP-MgCl2 pretreatment would attenuate ischemia-reperfusion-induced acute lung injury and to identify the possible mechanisms for such protection. Typical acute lung injury was successfully induced in Sprague-Dawley rats by 10 min of hypoxia followed by 75 min of ischemia and 50 min of reperfusion. Pretreatment with ATP-MgCl2 (or adenosine) but not ATP or MgCl2 (all at 10(-6) M) significantly attenuated the acute lung injury. All the protective effects of ATP-MgCl2 were nearly undetectable when promazine (an ecto-adenosinetriphosphatase inhibitor) or 3,7-dimethyl-1-propargylxanthine (an A2-receptor antagonist) was added before ATP-MgCl2 pretreatment. These observations support our hypothesis that the protective effect of ATP-MgCl2 is in part mediated through adenosine, the degradation product of ATP, which is produced by the Mg(2+)-dependent ecto-adenosinetriphosphatase on the surface of neutrophils and reacts with neutrophil A2 receptors to inhibit the production of O2 radicals.

Adenosine Triphosphate↗

PubMed1994

Physical conditioning decreases norepinephrine-induced vasoconstriction in rabbits. Possible roles of norepinephrine-evoked endothelium-derived relaxing factor.

BACKGROUND: Physical activity can reduce sympathetic tone and may be beneficial to human health. Whether the vascular responses to norepinephrine (NE), an adrenergic vasoconstrictor, could be altered by chronic exercise was unclear. We therefore conducted this study to investigate the effects of endurance exercise training on NE-induced vasoconstrictive response in healthy rabbits. Possible mechanisms were also studied. METHODS AND RESULTS: Twenty-four male New Zealand White rabbits were used for this study. They were divided into two groups: control and training. The training group was trained on a treadmill with running speed of 0.88 km/h at a 0 degree grade for 10 to 60 minutes per day, for 5 days a week for a total of 8 weeks. At the end of the experiments, thoracic aortae (3 mm long) were isolated. The vascular tension was measured with a force transducer. The dose-response relation of NE-induced vasoconstriction was determined and compared for control (n = 5) and trained (n = 6) groups. To verify the possible involvement of endothelium-derived relaxing factor (EDRF) in the alteration of NE-induced vasoconstriction after exercise training, we compared the vascular responses to NE in endothelium-intact, N omega-nitro-L-arginine (L-NNA, 10(-4) mol/L)-pretreated, or denuded vessel segments (n = 4 for each experiment of each group). EDRF release in the presence or absence of NE was also evaluated by the increased tension induced by hemoglobin (10(-5) mol/L), an EDRF scavenger (n = 6 for the control group and n = 8 for the trained group). In addition, vascular responses to some specific adrenergic agonists (ie, phenylephrine, an alpha 1-agonist, and clonidine, an alpha 2-agonist) were also studied to see if a specific adrenergic receptor was involved (n = 4 for each experiment of each group). Our results indicated that (1) [NE]ED50 of the thoracic aorta was elevated by exercise training; (2) in the presence of NE, EDRF release from the thoracic aorta, assessed by addition of hemoglobin or L-NNA, was higher in the trained group than in the control group; (3) both phenylephrine (10(-8) mol/L) and clonidine (10(-6) mol/L) could evoke vasorelaxation that would be inhibited by L-NNA; and (4) in addition to causing vasoconstriction, NE could stimulate EDRF release, possibly via alpha 1- and alpha 2-receptors of endothelial cells. CONCLUSIONS: Our data suggest that exercise training may decrease NE-induced vasoconstrictive response and may increase NE-stimulated EDRF release.

Animals↗

PubMed1994

Different effects of strenuous exercise and moderate exercise on platelet function in men.

BACKGROUND: Platelets play an important role in the pathogenesis of cardiovascular diseases. It is also noticed that on one hand, regular exercise can reduce the risk of cardiovascular diseases, and on the other hand, vigorous exercise provokes sudden cardiac death. We therefore hypothesize that various intensities of exercise may affect platelet function differently. METHODS AND RESULTS: Strenuous and moderate exercise (about 50% to 55% of peak oxygen consumption, VO2peak) on a bicycle ergometer in 10 sedentary and 10 physically active healthy young men was executed on two separate occasions. Blood samples were collected before and immediately after exercise. A newly designed tapered parallel plate chamber was used to assess platelet adhesiveness. Platelet aggregation induced by ADP was evaluated by the percentage of reduction in single platelet count. beta-Thromboglobulin (beta-TG) and platelet factor 4 (PF4) were measured by ELISA. In addition, a similar study on 5 patients with stable angina were also conducted. Our results showed that (1) in the sedentary healthy group, platelet adhesiveness and aggregation were increased by strenuous exercise and depressed by moderate exercise; (2) in the active healthy group, platelet adhesiveness and aggregation were enhanced by severe exercise, whereas only aggregation was decreased by moderate exercise; (3) in the patients with stable angina, platelet adhesiveness and aggregation were enhanced by strenuous exercise and adhesiveness was suppressed by moderate exercise; (4) the degree of hemoconcentration induced by acute exercise tended to be related to the severity of exercise in all subjects; and (5) although severe exercise elevated beta-TG and PF4, there were no significant changes in beta-TG, PF4, and the ratio of beta-TG to PF4 in healthy subjects after exercise. CONCLUSIONS: It is concluded that platelet adhesiveness and aggregability may be sensitized by strenuous exercise in both healthy subjects and patients with stable angina. In contrast, platelet function can be suppressed significantly by moderate exercise in the healthy and tends to be depressed in patients with stable angina. The former may increase the risk of cardiac arrest and the latter may protect us from cardiovascular diseases. In addition, the effects of acute exercise tend to be more pronounced in the sedentary than in the active.

Adult↗

PubMed1994

The direct cardiac effects of ketamine studied on the intact isolated rabbit heart.

The effects of ketamine on the inotropic and chronotropic responsiveness of heart were examined in spontaneously beating hearts isolated from rabbits by using a modified Langendorff preparation. The changes of maximum left ventricular dP/dt from baseline level after exposing to ketamine 5, 25 and 125 micrograms/ml averaged +7.1% (P < 0.05), +2.8% (P > 0.05) and -42.6% (p < 0.001), respectively. The decreases of heart rate at the three ketamine concentrations averaged 2.4% (P < 0.05), 9.4% (P < 0.01) and 36.8% (P < 0.001), separately. Our data demonstrate that ketamine has dual actions on the cardiac inotropism. It mildly increases cardiac contractility at low concentration whereas at high concentration it depresses myocardium profoundly. Besides, ketamine produces a dose-dependent inhibition on chronotropism directly.

Animals↗

PubMed1993

Pharmacological evaluation of the alpha-adrenoceptors of the rabbit urethra.

Nerve-mediated responses of the rabbit urethral smooth muscles were studied using electrical stimuli of short duration to selectively stimulate the intramural nerves. The nature of the responses to exogenously applied adrenergic agonists and its antagonists were also examined. The results confirmed that the rabbit urethral smooth muscle contains both subtypes of alpha-adrenoceptors and the nerve-mediated contraction of the rabbit urethra is of adrenergic nature and mediated mainly via alpha 1-adrenoceptors.

Adrenergic alpha-Agonists↗

PubMed1993

Evaluation of left ventricular functional status using thermodynamic indices.

Conventional methods to assess cardiac contractility have been focused on the mechanical properties of the myocardium. Many of these have suffered from theoretical and practical drawbacks. In this study, we have attempted to evaluate the left ventricular contractile status using the thermodynamic principle and compared these indices with the conventional index (dP/dt). A total of 8 mongrel dogs were anesthetized and artificially ventilated. A Millar catheter with high-fidelity multiple sensors was inserted into the aorta to record the simultaneous changes in aortic flow and pressure waves. Cardiac inotropy was increased by graded doses (2-32 micrograms/kg/min) of dobutamine. Angiotensin injection (100-300 micrograms) to achieve a blood pressure elevation of 30 mmHg was employed for afterload augmentation. Preload was increased by rapid infusion of 6% dextran solution (20 ml/kg). Several thermodynamic parameters were calculated at steady state during the control period and after drug interventions. These included power-averaged rate of power density generation (ARPD), peak ejection rate of change of power (PREP), energy-averaged power density (APD) and frequency-normalized ARPD (FARPD). PREP and APD were unchanged by afterload increment while FARPD, ARPD and dP/dt decreased significantly with an increase in afterload, ARPD was highly sensitive to an increased preload (p < 0.001), and PREP was also changed significantly by an increase in preload. dP/dt was boarderlinely affected by Dextran infusion (p = 0.05), and APD was independent of preload (P > 0.05). Inotropic stimulation increased ARPD, PREP, APD, FARPD and dP/dt by 139.0 +/- 48.0%, 98.0 +/- 51.4%, 74.0 +/- 49.7%, 60.0 +/- 30.4% and 44.6 +/- 10.4%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1993

Characterization of postsynaptic alpha-1 and alpha-2 adrenoceptors in the feline saphenous and femoral veins [corrected].

Experiments were designed to characterize the effects mediated by alpha-1 and alpha-2 adrenoceptors in saphenous and femoral veins of the cat. Ring segments of saphenous and femoral veins were mounted for isometric tension recording in modified Krebs-bicarbonate solution, gassed with 95% O2-5% CO2 and maintained at 37 degrees C. Norepinephrine (a mixed alpha 1 and alpha 2 agonist), phenylephrine (a preferential alpha 1 agonist) and clonidine (a preferential alpha 2 agonist) caused dose (concentration)-dependent contractions in saphenous and femoral veins. The maximal contractions produced by clonidine were significantly less than those produced by norepinephrine or phenylephrine in both veins. However, threshold dose and EC50 values indicated that clonidine was more potent than norepinephrine and phenylephrine. Contractile responses to these agonists were attenuated when the veins were pretreated with alpha 1-or alpha 2-adrenoceptor antagonists, prazosin and yohimbine, respectively. The contractile responses to norepinephrine and tyramine were inhibited to a greater extent by yohimbine than by prazosin in both saphenous and femoral veins, suggesting that norepinephrine released from perivascular nerve terminals activates preferentially postsynaptic alpha 2-adrenoceptors. Further examination of alpha-adrenoceptor subtypes was achieved by comparing pA2 values of prazosin and yohimbine from Arunlakshana and Schild plots. Chronic sympathetic denervation by removing lumbar sympathetic chain significantly reduced the contractile responses evoked by tyramine. Denervation did not significantly affect the concentration-response curve to phenylephrine but significantly augmented the contractile responses evoked by clonidine in both veins.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗