Biomedical subjects
Publications and source records attributed to C C Pang.
Chinese populations have been protected from coronary heart disease by a low fat diet and low plasma lipids. Fat intake has increased in more affluent populations but coronary heart disease mortality has remained relatively low. Further increases in dietary fat in young people and rising rates of diabetes in the older population may increase the prevalence of hyperlipidaemia and vascular disease.
The effects of endothelin-1 and vehicle (0.9% NaCl) on mean arterial pressure, heart rate, mean circulatory filling pressure, systemic arterial resistance, cardiac output and venous resistance were studied in four groups of pentobarbitone-anaesthetized rats, either in presence or absence of phentolamine. I.v. bolus injections of endothelin-1 at 0.5, 1 and 2 nmol/kg dose dependently increased mean arterial pressure (22, 34 and 40 mmHg), arterial resistance (33, 93 and 122% over baseline), venous resistance (40, 117 and 143% over baseline) and mean circulatory filling pressure (1.0, 1.7 and 1.8 mmHg), but decreased heart rate (-16, -21 and -17 beats/min) and cardiac output (-6, -28 and -35% below baseline). The vehicle did not significantly alter any of these variables. During the continuous infusion of phentolamine (300 microg/kg per min), endothelin-1 caused similar increases in arterial resistance, venous resistance and mean circulatory filling pressure, similar reduction in cardiac output but significantly greater pressor and bradycardic responses, suggesting that the arterial and venous constrictor effects of endothelin-1 are not due to sympathetic activation and the stimulation of alpha-adrenoceptors. The results show that endothelin-1 raised mean arterial pressure via the increment in systemic arterial resistance, since cardiac output was markedly reduced. This decrease in cardiac output was mediated by increases in arterial as well as venous resistances. The vasoconstrictor and venoconstrictor effects of endothelin-1 were independent of sympathetic tone.
N(G)-nitro-L-arginine (L-NNA) and D-NNA have been shown to inhibit endothelium-dependent relaxation. This study examined if the inhibitory effect of L-NNA or D-NNA on relaxation is increased following incubation of the drug with the supernatant of tissue homogenates. Acetylcholine (ACh) caused concentration-dependent relaxation of pre-constricted rat aortic rings with maximum relaxation of 95%. Maximum relaxations to ACh were reduced to 71 and 37% in the presence of D-NNA (40 microM) and L-NNA (1 microM), respectively. Relaxation to ACh was further reduced to 18% in the presence of D-NNA that was incubated for 1 h with the supernatant of kidney homogenate, but unaffected by D-NNA incubated with the supernatant of trichloroacetic acid-denatured kidney homogenate. Incubation of L-NNA (1 microM) with either kidney supernatant or denatured kidney supernatant for 1 h did not affect its inhibitory effect on ACh-induced relaxation. Neither 1 h's incubation with plasma, or supernatants of liver, lungs or aorta homogenates affected the inhibitory action of D-NNA (40 or 120 microM) on ACh-induced relaxation. After D-NNA was incubated in kidney supernatant, its inhibitory effect on ACh-induced relaxation of the aorta was abolished by pretreatment of the aorta with L-arginine (L-Arg) but not D-Arg suggesting involvement of the L-Arg pathway. The results suggest that D-NNA is converted by the kidney to a compound that acts similar to L-NNA. There appears to be little conversion of L-NNA to D-NNA.
1. The subtypes of endothelin receptors that mediate the effects of endothelin-1 (ET-1) on mean arterial pressure (MAP), heart rate (HR), mean circulatory filling pressure (MCFP), arterial resistance (RA), cardiac output (CO) and venous resistance (RV) were characterized in 9 groups of pentobarbitone-anaesthetized rats via the injection of ET-1 in the absence and presence of bosentan (Ro 47-0203, ETA- and ETB-receptor antagonist), PD 142893 (ETA- and ETB-receptor antagonist) or FR 139317 (ETA-receptor antagonist), as well as injection of the ETB-receptor agonist, IRL 1620. 2. Cumulative i.v. bolus injections of ET-1 or IRL 1620 (0.5, 1 and 2 nmol kg-1) dose-dependently increased MAP (ET: by 22, 34 and 44; IRL: 8, 17 and 28 mmHg), RA (ET: 62, 108 and 162; IRL: 51, 63 and 86% over baseline), RV (ET: 70, 132 and 179; IRL: 81, 89 and 98% over baseline) and MCFP (ET: 1.1, 1.8 and 1.9; IRL: 0.9, 1.0 and 1.2 mmHg) and reduced CO (ET: -18, -35 and -44; IRL: -24; -26; -25% below baseline). Equimolar doses of ET-1 and IRL 1620 caused similar initial transient depressor responses. Saline did not modify any haemodynamic variables in the time-control group. 3. Bosentan (10 mg kg-1, i.v.) inhibited ET-induced increases in MAP, RV, RA and MCFP and decrease in CO. PD 142893 (22 mg kg-1, i.v.) abolished ET-induced changes on MAP, RV, RA and CO, but did not alter effects on MCFP. Bosentan alone did not cause haemodynamic changes, but PD 142893 alone elevated MCFP (0.9 +/- 0.3 mmHg at 1 h after injection) and did not alter other variables. Both antagonists abolished the initial depressor effects of ET-1. 4. FR 139317 (1 mg kg-1, i.v.) partially inhibited the increases in MAP, RV, RA and MCFP and decreases in CO elicited by ET-1, but did not alter the transient depressor response of ET-1. 5. The results show that both ETA- and ETB-receptors mediate the arterial and venous constrictor effects of ET-1. Bosentan is more efficacious than PD 142893 in inhibiting the venous effects of ET-1.
We studied a variable number tandem repeat polymorphism within the dopamine transporter gene (DAT) for an association with Parkinson's disease in a Chinese population. Five alleles were detected, consisting of 6, 8, 9, 10, and 11 copies of the 40 base pair repeat sequence. The 10-copy allele was most common, accounting for 90% of alleles. There were no significant differences between the patients and the control subjects in the distribution frequencies of the alleles or genotypes. Therefore, this polymorphism is not associated with Parkinson's disease in Chinese populations.
OBJECTIVE: To assess fetal cellular injury arising from oxygen free radical activity in relation to the duration of the second stage of labor. PATIENTS AND METHODS: Cord arterial pH, malondialdehyde and organic hydroperoxides levels were determined following vaginal delivery of 326 term singleton pregnancies. Of these, 35 (11%) received epidural analgesia. The length of the second stage was recorded from the time of full dilatation to delivery. RESULTS: Arterial cord pH, malondialdehyde and organic hydroperoxides were significantly correlated with duration of second stage of labor (r=-0.4492; r=0.2542; r=0.2244; respectively, p<0.001). The association of lipid peroxidation products with second stage duration was independent of cord pH. This correlation was unchanged when cases of operative delivery were excluded. However, the relationship lost statistical significance amongst cases who received epidurals. CONCLUSIONS: The duration of the second stage is correlated with raised reactive oxygen species-derived lipid peroxidation products. Caution should be exercised in the management of prolonged second stage of labor.
The effects of NG-nitro-L-arginine (L-NNA), D-NNA, diphenyleneiodonium and di-2-thienyliodonium on contraction were studied in endothelium-denuded rat aortic rings incubated for 4 h with lipopolysaccharide (10 mu g ml-1) or vehicle. Lipopolysaccharide reduced Emax and increased EC50 of the phenylephrine (10-9-10-5 M) curve. Addition of D-NNA (4, 6 x 10-4 M), L-NNA (1, 10 x 10-6 M) and diphenyleneiodonium (1, 3 x 10-7 M), but not di-2-thienyliodonium (10-7 M), increased Emax and reduced EC50 of the phenylephrine curve of lipopolysaccharide-incubated but not control rings. Therefore, D-NNA, L-NNA and diphenyleneiodonium, but not di-2-thienyliodonium, inhibit inducible NO synthase in vascular smooth muscles.
OBJECTIVE: The purpose of this study was to determine oxygen free radical activity in the neonate at birth and relate it to umbilical cord blood acid-base status. STUDY DESIGN: A series of 110 singleton deliveries had determination of two lipoperoxides in umbilical cord blood: malondialdehyde and organic hydroperoxide. Umbilical pH, PO2, PCO2, bicarbonate, and base excess were also measured. RESULTS: There was a significant association between lipoperoxides and cord blood pH and base excess. A significant difference existed in the levels of umbilical artery lipoperoxides between nonacidemic and acidemic fetus, as defined by an umbilical arterial pH < 7.20. CONCLUSION: There is a positive association between lipoperoxide production and acid-base balance at delivery.
We examined the effects of D-NNA (NG-nitro-D-arginine) and L-NNA (NG-nitro-L-arginine) on suppression of Escherichia coli lipopolysaccharide (LPS)-induced vascular hyporeactivity in pentobarbital-anesthetized rats. Mean arterial pressure (MAP) and pressor response to norepinephrine (NE) were reduced at 40 min (early phase) and 3.5-4 h (late phase) after i.v. injection of LPS (10 mg/kg). Pretreatment with either D-NNA (16 mg/kg) or L-NNA (8 mg/kg) abolished LPS-induced reduction in MAP and hyporesponsiveness to NE during the early phase but not the late phase of endotoxemia and increased mortality. In contrast, posttreatment with D-NNA and L-NNA at 3 h after the injection of LPS prevented further decreases of MAP and pressor response to NE during the late phase of endotoxemia. The restoration of vascular response by pretreatment with either D-NNA or L-NNA during the early phases or posttreatment with either of these two agents during the late phase of endotoxemia was abolished by i.v. infusion (10 mg/kg/min) of L-arginine (L-Arg), but not D-arginine (D-Arg), suggesting involvement of the L-Arg/ nitric oxide pathway.
We previously reported that the renal arterial infusions of non-hypotensive doses of calcitonin gene-related peptide (CGRP) caused renal vasodilatation and increases in glomerular filtration rate at a low dose, but renal vasoconstriction, natriuresis and kaliuresis at a high dose. In the present study, we examined the effects of the specific CGRP1 receptor antagonist (CGRP-(8-37) (1 and 10 nmol/kg) and the putative CGRP receptor antagonist, [Tyr(0)]CGRP-(28-37)(3 and 30 nmol/kg), on the renal vascular and tubular effects of CGRP in inactin-anaesthetized Sprague-Dawley rats. Renal arterial infusion of single doses of CGRP (0.3-300 pmol/kg per min) did not significantly alter mean arterial pressure or heart rate. However, during the continuous renal arterial infusion of either CGRP-(8-37) or [Tyr(0)CGRP-(28-37) incompletely inhibited the vasoconstriction but did not inhibit diuresis, natriuresis and kaliuresis elicited by a high but non-hypotensive dose of CGRP. On the basis that CGRP-(8-37) is a competitive CGRP1 receptor antagonist, our results suggest: (1) the renal vascular effect of CGRP is completely mediated via the activation of CGRP1 receptors, (2) the renal tubular effects of CGRP are not mediated via CGRP1 receptors, and (3) [Tyr(0)]CGRP-(28-37) is a CGRP1 receptor antagonist with potency and efficacy less than those of CGRP-(8-37).
The effects of platelet activating factor (PAF) on haemodynamics in the absence and presence of the potent PAF receptor antagonist TCV-309 (3-bromo-5-[N-phenyl-N-[2-[[2-(1,2,3,4-tetrahydro-2- isoquinolyl-carbonyloxy)ethyl]carbamoyl]ethyl]carbamoyl]-1- propylpyridinium nitrate) were studied by the microsphere technique in pentobarbitone-anaesthetized rats. I.v. infusion of the low dose PAF (0.05 microgram kg-1 min-1) did not significantly alter mean arterial pressure, cardiac output or total peripheral resistance but increased arterial conductances in the stomach, intestine, caecum and colon and reduced conductance in the spleen. I.v. infusion of the high dose of PAF (0.3 microgram kg-1 min-1) markedly reduced mean arterial pressure (-53 mm Hg) and cardiac output (-62%) and insignificantly increased total peripheral resistance. Arterial conductances in the lungs, stomach, intestine, caecum and colon, kidneys and spleen were reduced and those in the heart and muscle were increased. TCV-309 (10 micrograms kg-1) abolished all changes in arterial pressure, cardiac output and total peripheral resistance and arterial conductances elicited by either the low or the high dose of PAF. The results show that a non-hypotensive dose of PAF caused vasodilatation of the gastrointestinal organs and vasoconstriction of the spleen. A high dose of PAF which markedly decreased arterial pressure and cardiac output caused vasodilatation of the heart and muscle and vasoconstriction of the lungs (bronchial), gastrointestinal organs, kidneys and spleen. All haemodynamic changes were blocked by TCV-309 indicating the involvement of PAF receptors.
1. The effects of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on mean circulatory filling pressure (MCFP), total peripheral resistance (TPR), cardiac output (CO) and resistance to venous return (Rv) were studied in rats. 2. In conscious, unrestrained rats, L-NAME (0.5-16 mg kg-1) dose-dependently increased mean arterial pressure (MAP) but not MCFP, an inverse index of venous compliance, either in the absence or presence of the ganglionic blocker mecamylamine (10 mg kg-1). 3. In pentobarbitone-anaesthetized rats, L-NAME (2, 4, 8 mg kg-1) increased MAP and reduced CO in a dose-related manner but did not change MCFP, TPR (+84, +140 and +192%) as well as Rv (+62, +72, +110%) were dose-dependently increased by L-NAME. 4. Our results show that L-NAME reduces CO by increasing arterial as well as venous resistances. L-NAME does not affect MCFP.
1. The vascular effects of the soluble guanylyl cyclase inhibitor, methylene blue as well as the nitric oxide (NO) synthase inhibitors, NG-nitro-L-arginine (L-NOARG) and diphenyleneiodonium (DPI) were studied in rat isolated aortic rings and conscious, unrestrained rats. 2. Acetylcholine (ACh) and sodium nitroprusside (SNP) caused concentration-dependent relaxation of preconstricted aortic rings. Both methylene blue (1 x 10(-5) M) and L-NOARG (3 x 10(-5) M) abolished ACh-induced relaxation; however, methylene blue but not L-NOARG shifted the concentration-response curve of SNP to the right. 3. In conscious rats, i.v. infusion of methylene blue (1.1 x 10(-5) mol kg-1 min-1), at a concentration which reduced the aortic tissue level of cyclic GMP by 50%, did not significantly alter mean arterial pressure (MAP) and heart rate (HR). In contrast, i.v. bolus injection of L-NOARG (1.5 x 10(-4) mol kg-1) markedly increased MAP and decreased HR. 4. Both ACh and SNP dose-dependently decreased MAP in conscious rats. Methylene blue did not alter the magnitude or duration of ACh- or SNP-induced depressor responses. L-NOARG, on the other hand, significantly though incompletely, reduced the magnitude and duration of the depressor response to ACh but not SNP. The depressor response to ACh or SNP was not altered by pretreatment with indomethacin (1.4 x 10(-5) mol kg-1) or capsaicin (3.3 x 10(-4) mol kg-1). 5. NG-nitro-L-arginine methyl ester (L-NAME) also caused dose-dependent increases in MAP in conscious rats. Both methylene blue and DPI (1 x 10-5 mol kg-1) selectively shifted the dose-pressor response curve of L-NAME to the right.6. These results suggest that: (1) the inhibition of endogenous NO biosynthesis does not necessarily lead to pressor response in vivo, (2) L-NOARG may not produce pressor response solely via the inhibition of endogenous endothelial NO biosynthesis, and (3) the depressor responses to ACh and SNP may not involve the release of NO or prostanoids or afferent nerve transmitters.
1. Adrenomedullin is a novel vasoactive peptide which is produced in the lungs, ventricle, kidneys, heart and adrenal medulla. Adrenomedullin shows homology to calcitonin gene-related peptide (CGRP) and has similar pharmacological actions to CGRP. 2. This study examined the dose-response effects of adrenomedullin (rat, 11-50) on mean arterial pressure (MAP), heart rate (HR), renal blood flow (RBF), glomerular filtration rate (GFR) and renal tubular electrolyte excretion in Inactin-anaesthetized Sprague Dawley rats. The possible involvement of CGRP receptors in actions of adrenomedullin was also examined via renal arterial injection of a CGRP receptor antagonist, CGRP (8-37) (1 or 10 nmol kg-1) or [Tyr0]CGRP(28-37) (3 or 30 nmol kg-1), starting 15 min prior to the administration of adrenomedullin. 3. Renal arterial infusion (0.001 to 1 nmol kg-1) of adrenomedullin did not alter MAP, HR and renal K+ excretion but dose-dependently increased RBF and arterial conductance, GFR, urine flow and Na+ excretion. 4. The renal actions of adrenomedullin were not blocked by either the low or the high dose of CGRP(8-37) or [Tyr0]CGRP(28-37). 5. The results show that adrenomedullin causes renal vasodilatation, increments in GFR, diuresis and natriuresis. The renal actions of adrenomedullin are not mediated via the activation of CGRP1 receptors.
1. The effects of the potassium channel opener, pinacidil, on mean arterial pressure (MAP), mean circulatory filling pressure (MCFP), total peripheral resistance (TPR), cardiac output (CO) and resistance to venous return (Rv) were studied in rats. 2. In pentobarbitone-anaesthetized rats given mecamylamine (ganglionic blocker, 3.7 micrograms kg-1) and noradrenaline (1.5 micrograms kg-1 min-1) to suppress autonomic reflexes, pinacidil (60 and 180 micrograms kg-1 min-1), relative to the vehicle, reduced MAP and TPR in a dose-dependent manner but did not significantly alter CO, MCFP or RV. 3. Pinacidil (10-300 micrograms kg-1 min-1) caused similar increases in MCFP, an inverse index of venous compliance, and similar dose-dependent reductions in mean arterial pressure (MAP) in conscious, intact rats and rats infused with the ganglionic blocker, hexamethonium (150 micrograms kg-1 min-1). In rats with vasomotor tone elevated by the infusion of noradrenaline (1.5 micrograms kg-1 min-1), pinacidil caused markedly greater depressor responses but did not significantly alter MCFP. 4. Our results show that pinacidil is an efficacious vasodilator of arterial resistance blood vessels but has little venodilator activity.
The existence of calcitonin gene-related peptide (CGRP) nerve fibers and CGRP receptors in the kidney and the coupling of the receptors to adenylyl cyclase suggest that CGRP participates in renal regulation. This study investigates the dose-effect relationship of CGRP on renal blood flow (RBF) and arterial conductance, glomerular filtration rate (GFR) and tubular excretion in Inactin-anesthetized, Sprague-Dawley rats. The contributions of endothelium-derived relaxing factor/nitric oxide in the renal actions of CGRP also were investigated via renal arterial injection of the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 0.5 or 5 mg/kg). Renal arterial infusion of CGRP (0.3-300 pmol/kg/min) did not affect mean arterial pressure or heart rate. Low doses of CGRP increased RBF, arterial conductance and GFR, but the highest dose reduced RBF and conductance without affecting GFR. High doses of CGRP also increased urine flow and excretions of Na+ and K+. The renal vasodilator but not the constrictor effect of CGRP was inhibited by both doses of L-NAME. The increase in GFR by the lowest dose of CGRP was attenuated by the low dose and abolished by the high dose of L-NAME. L-NAME did not inhibit the diuretic, natriuretic and kaliuretic effects elicited by high doses of CGRP. The results show that a low dose of CGRP causes renal vasodilatation via the release of endothelium-derived relaxing factor/nitric acid.
We characterized the contractile effect of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA) in endothelium-denuded rat aortic rings. Incubation with L-NNA (4 x 10(-6)-6.4 x 10(-5) M) for 5 h dose-dependently contracted endothelium-denuded aortic rings. In contrast, incubation with NG-nitro-D-arginine (D-NNA 6 x 10(-6)-4 x 10(-4) M), diphenyleneiodonium (DPI, NO synthase inhibitor, 3.2 x 10(-6) M) or dexamethasone (10(-7) M, inhibitor of expression of inducible NO synthase) did not contract the denuded rings. The L-NNA-induced contraction was not significantly altered by the presence of the endothelium or by pretreatment with L-arginine (L-Arg 2 x 10(-3) M) or lipopolysaccharide (100 ng/ml). These results suggest that L-NNA causes slow contraction of endothelium-denuded vascular smooth muscle (VSM) by a mechanism independent of the inhibition of constitutive or inducible NO biosynthesis.
1. It is known that activation of alpha 1-adrenoceptors causes renal vasoconstriction and increased tubular Na+ and water reabsorption, with the alpha 1a-subtype mediating the constrictor effect. 2. This study examines which subtype of alpha 1-adrenoceptors mediates tubular Na+ and water reabsorption in pentobarbitone-anaesthetized rats. In order to avoid systemic effects, phenylephrine (0.3 to 30 micrograms kg-1), methoxamine (0.1-10 micrograms kg-1) and vehicle were infused into the right renal artery (via the suprarenal artery) of three groups of rats. Two other groups of rats were continuously infused with the irreversible selective alpha 1b-adrenoceptor antagonist, chloroethylclonidine (3 mg kg-1 h-1) for 1 h, prior to the construction of dose-response curves to phenylephrine or methoxamine. Another group was continuously infused with the irreversible selective alpha 1a-adrenoceptor antagonist, SZL-49 (10 micrograms kg-1 h-1) for 1 h, prior to the construction of dose-response curves to phenylephrine. Mean arterial pressure (MAP), heart rate (HR), urine flow, Na+ and K+ excretion, and urine osmolality were monitored. 3. Phenylephrine and methoxamine did not affect MAP or HR but dose-dependently and significantly decreased urine flow, urine osmolality as well as Na+ excretion and, slightly increased K+ excretion, although this was significant only for phenylephrine. 4. The antidiuretic, antinatriuretic and kaliuretic effects of phenylephrine were abolished by pretreatment with chloroethylclonidine, but were not inhibited by SZL-49. The inhibitory effects of methoxamine on urine flow and Na+ excretion were also almost totally abolished by chloroethylclonidine. 5. Our results show that alpha 1b-adrenoceptors mediate renal tubular Na+ and water reabsorption.