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Biomedical subjects

C Wen

Publications and source records attributed to C Wen.

At least 37 records · Page 2Linked to original sources
PubMed1998

Hemodynamic profile of corticotropin-induced hypertension in the rat.

OBJECTIVES: To examine hemodynamic variables in corticotropin-induced hypertension in rats and the effects of reversal of the hypertension by L-arginine on the hemodynamic profile. METHODS: Sixty male Sprague-Dawley rats were randomly divided into four groups: sham treatment (0.9% NaCl, injected subcutaneously); 0.5 mg/kg corticotropin per day, subcutaneously; 0.6% L-arginine in food plus sham; and L-arginine plus corticotropin. Systolic blood pressure, water and food intakes, urine volume, and body weight were measured every second day. After 10 days mean arterial blood pressure was measured by intra-arterial cannulation, and cardiac output, and renal, mesenteric, and hindquarter blood flows were determined using transonic small animal flowmeters. RESULTS: Injection of corticotropin increased blood pressure, water intake, urine volume, and plasma sodium concentration, and decreased body weight and plasma potassium concentration. It increased cardiac output (P < 0.01), mesenteric blood flow (P < 0.05), and renal vascular resistance (P < 0.05), and decreased renal blood flow (P < 0.05), but did not change calculated total peripheral resistance, hindquarter blood flow, mesenteric or hindquarter vascular resistance. L-arginine prevented corticotropin-induced rises in blood pressure (P < 0.001) and renal vascular resistance (P < 0.05), and a fall in renal blood flow (P < 0.05), but did not affect other hemodynamic variables. CONCLUSION: The hemodynamic profile of corticotropin-induced hypertension in the rat is characterized by a rise in cardiac output and renal vascular resistance, a fall in renal blood flow, but no change in total peripheral resistance, hindquarter blood flow, mesenteric vascular resistance, or hindquarter vascular resistance. L-arginine prevented corticotropin-induced rises both in blood pressure and in renal vascular resistance in the rat. These data suggest that the increase in renal vascular resistance might play a role in corticotropin-induced hypertension in the rat.

Adrenocorticotropic Hormone↗
PubMed1998

Adrenocorticotrophin dose-response relationships in the rat: haemodynamic, metabolic and hormonal effects.

OBJECTIVE: To determine adrenocorticotrophin dose-response relationships for increase of blood pressure and metabolic parameters of the Sprague-Dawley rat. METHODS: We injected 120 male Sprague-Dawley rats twice daily subcutaneously for 10 days with 0.5, 1, 5, 50, 100, 200 or 500 microg/kg synthetic adrenocorticotrophin per day (all n = 10) or subjected them to sham injection (0.9% NaCl; n = 50). Systolic blood pressure, 24 h food intake, water intake, urine volume and body weight were measured. Data from a further 45 rats treated with 500 microg/kg per day adrenocorticotrophin in previous studies were included in the blood pressure analyses. After we had killed these rats, their organ weights (kidney, heart, adrenal) and plasma electrolyte, adrenocorticotrophin and serum corticosterone concentrations were measured. RESULTS: On the final day of treatment systolic blood pressure of sham-injection control rats was 123 +/- 1 mmHg (n = 50). Compared with sham treatment, a low dose of adrenocorticotrophin (1 microg/kg per day) increased systolic blood pressure from 122 +/- 1 to 130 +/- 2 mmHg (P < 0.001) without any metabolic effects, whereas a high dose of adrenocorticotrophin (500 microg/kg per day) increased systolic blood pressure from 121 +/- 1 to 150 +/- 2 mmHg (P < 0.001, n = 55) with increases in intake of water and urine volume (P < 0.001, n = 10) and a decrease in body weight (P < 0.001, n = 10). Plasma adrenocorticotrophin and serum corticosterone concentrations for the sham-injection control group were 162 +/- 12 pg/ml (36 +/- 3 pmol/l) and 376 +/- 18 ng/ml (1038 +/- 50 nmol/l), respectively. Plasma adrenocorticotrophin concentration was elevated by injections of 100 (P < 0.05), 200 (P < 0.01) and 500 microg/kg adrenocorticotrophin per day (P = 0.001). Serum corticosterone concentration was not significantly different from that of sham-injection rats with 0.5-5 microg/kg adrenocorticotrophin per day but was increased by injection of 50-500 microg/kg adrenocorticotrophin per day (P < 0.001). CONCLUSIONS: These results define 1 microg/kg adrenocorticotrophin per day, administered subcutaneously, as the threshold dose for causing a rise in blood pressure in the rat Thus administration of adrenocorticotrophin increases systolic blood pressure at doses that induce minimal adrenocorticotrophin metabolic effects. Administration of a low dose of adrenocorticotrophin to the rat is a suitable model for stress-induced hypertension.

Administration, Cutaneous↗
PubMed1998

Post-therapy iodine-131 localization in unsuspected large renal cyst: possible mechanisms.

Sensitive and specific, whole-body 131I scintigraphy remains an important technique for diagnosing metastases from differentiated papillary or follicular thyroid carcinoma. False-positive 131I localization is well recognized and can occur in a variety of conditions. We present a case of intense 131I localization in a previously unsuspected large renal cyst; the lesion was not visualized on routine preablation diagnostic 131I scintigraphy but was obvious on post-therapeutic whole-body imaging, underscoring the value of post-therapy imaging in detecting abnormalities not apparent on diagnostic studies. Radioiodine within the urinary bladder or, at times, the renal collecting system is expected, because 131I excretion is primarily by glomerular filtration. In the case presented here, 131I activity within the renal cyst supports the concept that iodide is subject to an active secretory process by the renal tubule.

Carcinoma, Papillary↗
PubMed1997

Fibronectin-fragment-induced cartilage chondrolysis is associated with release of catabolic cytokines.

Fibronectin fragments have both catabolic and anabolic activities toward articular cartilage explants in vitro. Whereas a 1 nM concentration of an N-terminal 29 kDa fibronectin fragment (Fn-f) increases the proteoglycan (PG) content of cartilage without induction of matrix metalloproteinases (MMPs), 0.1-1 microM Fn-f temporarily suppresses PG synthesis and enhances MMP release. The higher concentrations cause an initially rapid PG depletion during the first week of culture, followed by much slower PG loss and gradually increasing rates of PG synthesis. To test for the involvement of mediators, human articular cartilage was cultured with Fn-f, and conditioned media were assayed for selected cytokines and factors. With 1 nM Fn-f, the release of the anabolic factors, insulin growth factor-I and transforming growth factor beta1, from cultured cartilage was enhanced by 50-100% during the entire 28-day culture period and this was associated with both supernormal rates of PG synthesis and PG content. However, the higher concentrations of Fn-f additionally enhanced release, by at least 10-fold, of the cytokines, tumour necrosis factor alpha, interleukin-1alpha, interleukin-1beta and interleukin-6 while causing depletion of cartilage PG. Release of tumour necrosis factor alpha, interleukin 1beta and interleukin 1alpha peaked at days 2, 3 and 9 during or slightly after the period of maximal PG depletion and decreased to control levels by days 7, 7 and 21 respectively, whereas release of interleukin 6 was enhanced throughout the culture period. Neutralizing antibodies to the catabolic cytokines reduced Fn-f-mediated MMP-3 release and suppression of PG synthesis. The temporal aspects of this interplay between catabolic and anabolic factors are consistent with the kinetics of Fn-f-mediated cartilage damage and attempted repair and may be relevant to cartilage damage and repair in vivo.

Age Factors↗
PubMed1997

Agents that block fibronectin fragment-mediated cartilage damage also promote repair.

OBJECTIVE AND DESIGN: The objective was to determine if agents that suppress catabolism might also enhance repair of irreversibly damaged cartilage. MATERIAL: Articular cartilage from bovine metacarpophalangeal joints was studied in explant culture. TREATMENT: Fibronectin fragments or IL-1 alpha, which potently cause proteoglycan (PG) loss from cartilage, were added to cultures also containing the catabolism-blocking agents: insulin-like growth factor-1, or N-acetylcysteine, or Arg-Gly-Asp-Ser peptide, and the effects of these agents on blocking PG loss determined. To test for repair or restoration of PG, cartilage was first damaged, damage agents removed and inhibitory agents added. METHODS: Each mean and SD value for cartilage PG content was determined by assays of papain digests of cartilage from three similar cultures. RESULTS: The agents either partially or fully blocked PG loss and promoted repair. CONCLUSIONS: Normally irreversible cartilage damage was reversed by slowing ongoing catabolic processes during attempted repair. Thus, catabolic inhibitors have reparative potential.

Acetylcysteine↗
PubMed1997

Hemodynamic effects of the Fab fragment of digoxin antibody (digibind) in corticotropin (ACTH)-induced hypertension.

To determine whether the immune Fab fragment of digoxin antibody (digibind) attenuates established corticotropin (ACTH) hypertension, rats were given ACTH sham control (0.1 mL normal saline, twice daily, subcutaneously, n = 18) or ACTH treatment (2.5 microg/kg in 0.1 mL normal saline, twice daily, subcutaneously; n = 27) for 10 days. Acute hemodynamic effects of digibind (30 mg/kg, intravenous bolus injection) were examined after 10 days of sham control or ACTH treatment. Rats were divided into 7 groups: digibind (30 mg/kg, in 1 mL 0.9% NaCl intravenous bolus injection) plus sham (n = 6) or ACTH (n = 8), sham digibind (1 mL 0.9% NaCl intravenous bolus) plus ACTH (n = 7), digibind vehicle (sorbitol 1.8 mg in 1 mL 0.9% NaCl, intravenous bolus) plus sham (n = 6), preimmune sheep IgG (30 mg/kg in 1 mL 0.9% NaCl intravenous bolus) plus sham (n = 6) or ACTH (n = 6) and preimmune sheep IgG (Fab)2 fragment (30 mg/kg in 1 mL 0.9% NaCl intravenous bolus) plus ACTH (n = 6). ACTH increased systolic blood pressure (SBP) from 118 +/- 2 to 132 +/- 3 mm Hg on treatment day 10. BP was unchanged in sham treated rats. The acute administration of digibind decreased MAP (-14 +/- 3 mm Hg, P <.001) in ACTH hypertensive rats, but not in ACTH sham control normotensive rats (+2 +/- 3 mm Hg). Blood pressure reached a minimum after 14 +/- 3 min and the effect lasted more than 30 min. No significant change of blood pressure was found in ACTH treated rats receiving sham (0.9% NaCl) digibind injection (+2 +/- 2 mm Hg). However, both preimmune sheep IgG and IgG (Fab)2 fragment caused a decrease of blood pressure in both sham or ACTH treated rats. Although these data that digibind decreases BP in ACTH but not sham treated rats are consistent with the notion that digitalis-like substances may play a role in ACTH induced hypertension, the evidence that both preimmune sheep IgG and IgG (Fab)2 fragments also decreased blood pressure in rats suggests caution in interpretation of studies that employ digibind preparations.

Adrenocorticotropic Hormone↗
PubMed1997

Hyaluronic acid suppresses fibronectin fragment mediated cartilage chondrolysis: II. In vivo.

Intra-articular sodium hyaluronic acid (HA) has been used as a treatment intervention in the management of osteoarthritis. It has been observed that HA can coat the articular surface, and thus, has been suggested to provide a possible prophylactic barrier for the articular cartilage. In an accompanying manuscript (Homandberg et al.), we report that a commercially available high-molecular-weight HA (approximately 800-kDa, ARTZ, Seikagaku Corp.) can partially block fibronectin fragment (Fn-f)-mediated cartilage injury in vitro. Herein we report a study of the effects of intra-articular HA on an in vivo animal model of Fn-f-mediated cartilage injury. Rabbit knees were injected with Fn-f, and after 1 week, the cartilage proteoglycan (PG) content had decreased to 59 +/- 8% of control. In sharp contrast, PG content in knees receiving pre-treatment with HA followed by Fn-f injection had only decreased to 85 +/- 27% of control (P < 0.01). Similarly, the PG content in knees receiving an injection of Fn-f, followed by an injection of HA were significantly higher (74 +/- 18% of control) than Fn-f injured knees with no treatment (P < 0.02). Intra-articular HA alone had no effect on cartilage PG content. The results in this study suggest that HA is effective in partially preventing Fn-f mediated cartilage injury, most likely by coating the articular surface. Further, HA treatment after Fn-f injury may facilitate restoration of matrix components.

Animals↗
PubMed1997

Hyaluronic acid suppresses fibronectin fragment mediated cartilage chondrolysis: I. In vitro.

A commercial preparation of 800-kDa hyaluronic acid (HA), (ARTZ from Seikagaku, Inc.), has been used as a therapeutic intervention in the treatment of osteoarthritis (OA). We tested the effect of this HA form, HA/800, in an in vitro cartilage chondrolytic system in which a specific amino-terminal 29-kDa fragment of fibronectin (Fn-f) penetrates cartilage tissue to activate chondrocytes to amplify two major chondrolytic activities: suppression of proteoglycan (PG) synthesis and induction of matrix metalloproteinases. We report that HA/800 did not block damage by Fn-f in serum free cartilage cultures. However, HA/800 was effective in blocking the ability of 100 nM Fn-f to cause the degradation and release of half of the total cartilage PG from cartilage in 10% serum/DMEM cultures. While the Fn-f caused a half-time for PG release of 3 days, continuous exposure to 0.1 or 1 mg/ml HA/800 slowed the half-time to 12 days. Further, a single 1 day pre-incubation with 0.1 or 1 mg/ml HA/800 was sufficient to decrease the half-time of 100 nM Fn-f mediated PG depletion to 7 and 12 days, respectively. HA/800 completely blocked the effect of 10 nM Fn-f. Blocking of Fn-f-mediated cartilage PG depletion was associated with a decreased concentration of Fn-f on the superficial cartilage surface and decreased penetration into the cultured cartilage tissue. Further, the two major chondrolytic activities of the Fn-f, suppression of synthesis of PG and enhanced release of stromelysin-1, were suppressed by HA/800. HA/800 also partially restored PG in cartilage first damaged with the Fn-F. We conclude that HA/800 slows Fn-f-mediated cartilage chondrolysis in vitro and has some reparative potential. The damage blocking activity appears to be associated with the ability of HA/800 to block penetration of the Fn-f, rather than with direct effects on cartilage tissue.

Animals↗
PubMed1997

SUP-17, a Caenorhabditis elegans ADAM protein related to Drosophila KUZBANIAN, and its role in LIN-12/NOTCH signalling.

LIN-12/NOTCH proteins mediate cell-cell interactions that specify cell fates. Previous work suggested that sup-17 facilitates lin-12 signalling in Caenorhabditis elegans. Here, we show that sup-17 encodes a member of the ADAM family of metalloproteases. SUP-17 is highly similar to Drosophila KUZBANIAN, which functions in Drosophila neurogenesis, and the vertebrate ADAM10 protein. Furthermore, we show by genetic analysis that the extracellular domain of LIN-12 appears to be necessary for sup-17 to facilitate lin-12 signalling and that sup-17 does not act downstream of lin-12. Finally, we show by cell ablation experiments that sup-17 can act cell autonomously to facilitate lin-12 activity. We discuss the implications of our observations for LIN-12/NOTCH signalling and how our results complement and extend results obtained from genetic analysis of kuz in Drosophila.

ADAM Proteins↗
PubMed1997

[Clinical analysis of 7 cases of mesenteric venous thrombosis].

7 patients with mesenteric venous thrombosis (MVT) were treated in Anzhen Hospital from 1984 to 1996. The patients were all operated on and the diagnosis was confirmed pathologically. Fine patients were cured and 2 died. We discussed the pathophsiology, pathogeny, clinical manifestation, diagnosis and treatment of MVT. Most of the patients presented with a clinical picture of acute abdomen and the diagnosis was made only at laparotomy. Close observation and proper laparotomy should be given to the doubtful cases. To reduce the mortality rate of MVT, we resected the bowel which looks normal in appearance but comprises the mesentery of thrombosis. Adequate anticoagulant therapy should be given as early as possible.

Adult↗
PubMed1996

Fibronectin fragment mediated cartilage chondrolysis. II. Reparative effects of anti-oxidants.

In an accompanying manuscript, it was shown that the cartilage chondrolytic activities of fibronectin fragments (Fn-f), which are mediated through catabolic cytokines such as TNF-alpha, IL-1 and IL-6, could be suppressed by anti-oxidants (AOs). The AOs neutralized reactive oxygen species (ROS) which are known to mediate catabolic cytokine action. The objective in this work was to test whether AOs would promote restoration of proteoglycan (PG) in Fn-f treated cartilage, since under normal culturing conditions, PG is not restored after removal of the Fn-f. Cartilage was first cultured with an amino-terminal 29-kDa Fn-f to cause loss of about half of the total PG and then treated with NAC (1 and 10 mM) or glutathione (10 microM) or DMSO (0.1 or 1%). Treatment with NAC and glutathione maximally caused restoration of PG within 14 days to normal or supernormal levels, while DMSO was less effective. Catalase, but not superoxide dismutase, enhanced PG content to a small but significant extent. The restoration of PG in Fn-f treated cartilage occurred throughout the full depth of the cartilage slices as shown by histochemical analysis. However, removal of the AO allowed a subsequent decrease in PG content suggesting that the AOs had not blocked cytokine expression but had merely suppressed cytokine activities. Addition of NAC to IL-1 treated cartilage promoted a restoration of PG, while addition to chymopapain or trypsin treated cartilage was not very effective, suggesting that the effect of AOs requires a cytokine driven damage system. We conclude that the AOs promote a restoration of PG in the Fn-f treated cartilage by suppressing the effects of catabolic cytokines. The data suggest a potential for AOs in reversing tissue damage caused by cytokines.

Acetylcysteine↗
PubMed1996

Fibronectin fragment mediated cartilage chondrolysis. I. Suppression by anti-oxidants.

Fibronectin fragments damage cartilage in vitro by greatly enhancing metalloproteinases and suppressing proteoglycan (PG) synthesis which results in severe cartilage PG depletion. Since reactive oxygen species (ROS) have been implicated in catabolic cytokine action and preliminary data suggested that catabolic cytokines such as TNF-alpha, IL-1 alpha, IL-1 beta and IL-6 are responsible for fibronectin fragment mediated damage, selected anti-oxidants (AOs) were tested as inhibitors of cytokine. ROS and fibronectin fragment activity. Damage was measured by depletion of cartilage PG during tissue culture. The AO, N-acetylcysteine (NAC), decreased the extent of cartilage PG depletion caused by TNF-alpha and IL-1 alpha and by the ROS, hydrogen peroxide and superoxide anion, confirming that the cytokines operate through ROS and that ROS can initiate cartilage PG depletion. NAC at 0.1 and 1 mM, totally suppressed PG depletion caused by a highly potent amino-terminal 29-kDa fibronectin fragment (Fn-f) for 14 days in culture. NAC at 10 mM totally blocked Fn-f mediated PG depletion for 21 days and increased the cartilage PG content by 30% above normal levels. Glutathione (10 microM) and DMSO (1%) were also totally effective while catalase and superoxide decreased Fn-f mediated damage only during the first week and superoxide dismutase alone caused damage after 1 wk. The AOs caused protection by reducing the major catabolic activities of the Fn-f: enhanced release of stromelysin-1 (MMP-3) and suppression of PG and protein synthesis. NAC also decreased normal rates of PG degradation and increased the half-lives of labeled PG in both control and Fn-f treated cartilage. We conclude that the Fn-f mediates cartilage chondrolysis through ROS, consistent with the involvement of catabolic cytokines in the Fn-f mechanism, and that AOs greatly reduce Fn-f mediated cartilage chondrolysis. In an accompanying manuscript we also report that AOs promote reparative responses in Fn-f and cytokine treated cartilage.

Allopurinol↗
PubMed1996

Fibronectin fragments induce the expression of stromelysin-1 mRNA and protein in bovine chondrocytes in monolayer culture.

Addition of proteolytically generated fibronectin fragments (Fn-f) to cultured cartilage tissue causes greatly enhanced release of metalloproteinases (MMPs), such as pro-stromelysin-1 (proSln-1), and suppression of proteoglycan (PG) synthesis, through release of catabolic cytokines, while native fibronectin is ineffective. We have investigated whether enhanced release of proSln-1 was due to up-regulation of pro-Sln-1 mRNA. We report the addition of a 29-kDa (amino-terminal heparin-binding Fn-f) or a 140-kDa (central cell-binding Fn-f) to bovine chondrocytes in monolayer culture causes a dose dependent increase in the expression of pro-Sln-1 mRNA and the greatly enhanced release of pro-Sln-1 protein into the culture media. Up to 700 nM pro-Sln-1 was found in the conditioned media and metabolic labeling showed that it constituted a major portion of newly synthesized protein. A potential activator of pro-Sln-1, urokinase (u-PA), was released at elevated levels in the presence of the Fn-f while other activators, tissue plasminogen activator (t-PA) and plasmin activities were not detected. Addition of these activators to conditioned media did not allow conversion of pro-Sln-1 to active Sln-1. However, aminophenyl mercuric acid activated pro-Sln-1 to a 48-kDa Sln-1 form capable of degrading PG when added to cartilage suspensions. Gelatinase A mRNA was also enhanced, suggesting that the Fn-f may induce MMPs in general. However, the major regulator of Sln-1 activity, tissue inhibitor of MMPs form 1 (TIMP-1), was not induced at the gene level. Thus, a major effect of Fn-f on chondrocytes is to up-regulate pro-Sln-1 expression at the gene level, resulting in pro-Sln-1 as a major protein product.

Animals↗
PubMed1996

Angiotensin converting enzyme inhibition and protein restriction in progression of experimental chronic renal failure.

This study examined whether the effects of protein restriction and angiotensin converting enzyme (ACE) inhibition on the progression of renal failure are common or additive. Male Sprague Dawley rats (12 wks of age) underwent 5/6 nephrectomy and were randomized to 20% protein diet (PD) (n = 9), 20% PD+enalapril (5 mg/kg/day) (n = 10), 20% PD+felodipine (30 mg/kg/day) (n = 9), 6% PD (n = 9), 6% PD+enalapril (n = 9) or 6% PD+felodipine (n = 10). Protein restriction, enalapril or felodipine treatment all retarded progression of renal failure and development of glomerular lesions. Protein restriction and enalapril appeared to have additive effects in preventing glomerular sclerosis.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Validation of transonic small animal flowmeter for measurement of cardiac output and regional blood flow in the rat.

The objective of the present study was to validate a transonic flowmeter system with two probes (model 3SS for cardiac output (CO) and 1RB for organ flows) in Sprague-Dawley (SD) rats first by measuring blood flow through pump-infused isolated renal artery and ascending aorta, and then through measurements of CO and renal, mesenteric, and hindquarter blood flow (RBF, MBF, HBF) in vivo. We measured in vivo baseline flow and changes in flow induced by dopamine and propranolol for CO, prostaglandin E2 (PGE2), and angiotensin II (AII) for RBF and pentobarbital sodium for MBF and HBF. Correlations between meter and pump flow were linear (r = 0.999, p < 0.001) with close agreement both in ascending aorta and renal artery flow measurements. The baseline values were 15 +/- 0.7 ml/100 g/min for CO, 4 +/- 0.1 ml/100 g/min for RBF, 7 +/- 0.3 ml/100 g/min for MBF, and 6 +/- 0.3 ml/100 g/min for HBF, respectively. The system reliably detected increase and/or decrease in CO and regional blood flows. The transonic flowmeter system is accurate, highly reproducible, and compatible with other established techniques for measuring CO and regional blood flows in the rat.

Angiotensin II↗
PubMed1996

Dehydroepiandrosterone does not prevent adrenocorticotrophin-induced hypertension in conscious rats.

1. We tested the hypothesis that dehydroepiandrosterone (DHEA), which prevents dexamethasone-induced hypertension in rats, may block adrenocorticotrophin (ACTH) hypertension, which has been presumed due to corticosterone excess. The blood pressure and metabolic effects of DHEA (18 mg/kg per day) were examined in sham and ACTH-treated (0.5 mg/kg per day) conscious Sprague-Dawley rates (n = 20). 2. ACTH but not sham injection increased blood pressure, water intake and urine output and decreased bodyweight. 3. DHEA administration for 10 days did not alter blood pressure or metabolic effects in either sham or ACTH-treated rats. 4. DHEA, which is known to block dexamethasone-induced hypertension, did not modify ACTH-induced hypertension in the rat. This suggests either that ACTH-induced hypertension is not simply a consequence of glucocorticoid activity or that the action of DHEA in dexamethasone hypertension is not through blocking the glucocorticoid receptor.

Adrenocorticotropic Hormone↗
PubMed1996

L-arginine prevents corticotropin-induced increases in blood pressure in the rat.

In this study we examined whether L-arginine treatment could prevent corticotropin (ACTH)-induced increases in blood pressure in the Sprague-Dawley rat. Sixty rats were randomly divided into six groups (n = 10): sham injection, ACTH injection (0.5 mg/kg per day in divided doses), L-arginine (0.6%) in food plus sham injection, L-arginine plus ACTH treatment, D-arginine (0.6%) in food plus sham injection, and D-arginine plus ACTH. Systolic pressure, water intake, urine volume, body weight, plasma and urinary electrolytes, and serum corticosterone concentrations were measured. ACTH increased systolic pressure (from 127 +/- 2 to 165 +/- 6 mm Hg, P < .001), water intake, and urine volume and decreased body weight body weight. L-Arginine reduced ACTH-induced blood pressure rises (130 +/- 3 mm Hg, P < .001) but had no effect on blood pressure in sham-treated rats. D-Arginine did not affect blood pressure in sham-treated rats, and systolic pressure in D-arginine+ACTH-treated rats was similar to that of ACTH-treated rats. L-Arginine decreased serum corticosterone concentrations in sham-treated rats (424 +/- 42 versus 238 +/- 25 ng/mL, P < .01), but D-arginine had no effect. However, both drugs decreased serum corticosterone concentrations in ACTH-treated rats (1071 +/- 117 versus 739 +/- 95 and 695 +/- 72 ng/mL for L- and D-arginine, respectively; both P < .05). As L-arginine but not D-arginine prevented ACTH-induced increases in blood pressure in Sprague-Dawley rats and both L- and D-arginine reduced serum corticosterone concentrations in ACTH-treated rats, the effects of L-arginine in preventing ACTH-induced hypertension were not simply a consequence of decreased corticosterone secretion.

Adrenal Glands↗