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PubMed2004

[Mobilization of autologous peripheral blood stem cells with etoposide and recombinant human granulocyte colony stimulating factor in malignant tumor patients].

OBJECTIVE: To observe the combined effect of etoposide (Vp-16) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) on mobilization of autologous peripheral blood stem cells (APBSC) in malignant tumor patients and find out the suitable dose of Vp-16. METHODS: Thirty patients were randomly divided into two groups, 15 in each group. In group A, Vp-16 1000 mg/m(2) was injected intravenously in six divided doses, for 2 hours every 12 hours on day 1, 2 and 3. In group B, Vp-16 1500 mg/m(2) was injected intravenously in six divided doses for 3 hours every 12 hours on day 1, 2 and 3. rhG-CSF was given as a single daily injection subcutaneously at the dose of 300 microg.body(-1).day(-1) from the day of the nadir of white blood cell (WBC) to the day before the end of APBCS harvest. APBSC harvest started when WBC > or = 5.0 x 10(9)/L and finished when accumulated mononuclear cells (MNC) > or = 5 x 10(8)/kg or CD34+ cells > or = 2 x 10(6)/kg. RESULTS: There was no significant difference between the time of nadir, nadir of WBC, absolute neutrophil count (ANC), the beginning time and continuous time of rhG-CSF given, the beginning time and continuous time of APBSC harvest. When the blood volume, flow rate and continuous time of apheresis were similar in each apheresis in the two groups, the number of APBSC in each harvest and total number of APBSC were also not significantly different between the two groups. The side effects induced by Vp-16 were also not significant different between the two groups. CONCLUSION: Vp-16 combined with rhG-CSF is a safe and highly effective method for APBSC mobilization, 1000 mg/m(2) and 1500 mg/m(2) of Vp-16 possess similar efficiency and side effects for APBSC mobilization.

Adolescent↗
PubMed2006

[Proliferation inhibition and apoptosis induction of K562 cells by D-limonene].

This study was aimed to investigate the effect of D-limonene on K562 leukemia cells and its mechanism. Inhibitory effect of D-limonene on proliferation of K562 leukemia cells was assayed by MTT method and cell apoptosis was detected by flow cytometry and DNA agarose gel electrophoresis, the morphologic change of K562 cells was observed by microscopy. The results showed that when K562 cells were treated with 0.125 - 1.0 mmol/L of D-limonene for 48 hours, the proliferation of K562 cells was obviously inhibited in dose-dependent manner. Typical morphological changes and the typical DNA ladder on agarose gel electrophoresis for analysis of cellular apoptosis were significantly appeared in D-limonene treated K562 cells. Simultaneously, the sub-G1 peak was found in FCM analysis. It is concluded that the D-limonene can inhibit proliferation of K562 cells in dose-dependent manner, cause cell detained at G1 phase and induce apoptosis of K562 cells.

Antineoplastic Agents↗
PubMed2007

[Infection status and clinical significance of Epstein-Barr virus in pediatric leukemia---a report of 35 cases].

BACKGROUND & OBJECTIVE: Epstein-Barr virus (EBV) is associated with genesis of many human tumors. This study was to detect EBV infection in pediatric leukemia, and to explore its clinical significance. METHODS: EBV DNA in peripheral blood mononuclear cells in 35 pediatric leukemia patients, including 26 cases of acute lymphoblastic leukemia (ALL) (24 received initial treatment and 2 received retreatment), 8 cases of acute non-lymphocytic leukemia (ANLL) and 1 case of chronic lymphocytic leukemia (CLL), and in 14 healthy children was detected by fluorescent quantitative polymerase chain reaction (FQ-PCR). Its clinical significance was analyzed according to the clinical manifestations, prednisone sensitivity test, and complete remission (CR) rate after induction chemotherapy. RESULTS: EBV DNA was detected in 8 (22.86%) of the 35 pediatric leukemia patients. The positive rate of EBV DNA was 26.92% (7/26) in ALL with quantity of (5.144+/-6.91)x10(5) copies/ml, and 12.5% (1/8) in ANLL patients with quantity of 4.031x10(3) copies/ml. No EBV DNA was detected in CLL patients and healthy controls. The occurrence rates of peripheral leukocytosis and hepatosplenomegaly were significantly higher in the patients with EBV infection than in the patients without EBV infection (P <0.001). In ALL, the rate of no response to prednisone was significantly higher in the patients with EBV infection than in the patients without EBV infection (100% vs. 26.32%, P =0.001); CR rate after induction chemotherapy was significantly lower in the patients with EBV infection than in the patients without EBV infection (28.57% vs. 84.21%, P=0.003). In ANLL, the differences of CR rate and relapse rate were not significant between the patients with and without EBV infection (P=0.5). CONCLUSIONS: Pediatric leukemia patients with EBV infection have higher incidence of peripheral leukocytosis and hepatosplenomegaly. ALL patients with EBV infection have poor prednisone response and low CR rate.

Antineoplastic Agents, Hormonal↗
PubMed2004

Sequencing of endocrine therapy in postmenopausal women with advanced breast cancer.

The introduction of the nonsteroidal aromatase inhibitor (NS-AI) anastrozole as an alternative to tamoxifen for adjuvant therapy of women with resected hormone receptor-positive breast cancer has added a management category into which patients presenting with metastatic disease can be placed. There are now essentially three such categories: (a) tamoxifen sensitive (no prior AI); (b) tamoxifen resistant (no prior AI); and (c) NS-AI resistant (no prior tamoxifen). Well-conducted Phase III trials provide evidence for choosing first-line therapy for advanced disease in categories a and b. In tamoxifen-sensitive patients, one can choose either NS-AI, anastrozole, or letrozole. In tamoxifen-resistant patients, one can choose either of the NS-AIs, the steroidal AI exemestane, or the estrogen receptor down-regulator fulvestrant. The situation is quite different for patients in category c. There are no Phase III trials of agents in patients who have experienced disease progression on a NS-AI. Phase II data are available for exemestane and high-dose estrogens, and retrospective data are available for tamoxifen and fulvestrant. Additional clinical trials are needed to determine an optimal sequencing strategy.

Androstadienes↗
PubMed1998

[Treatment strategy for recurrent breast cancer].

In recent years, many kinds of efficacious modalities have been available for the treatment of recurrent breast cancer. Endocrine therapy is essentially the treatment of choice for both premenopausal and postmenopausal patients. The recommended sequence of endocrine therapies is described as follows: In premenopausal women, ovarian ablation (LH-RH agonists) is considered the first-line therapy, with tamoxifen (TAM) and aromatase inhibitors (AI) as the second-line alternatives. In postmenopausal women, the recommended first and second-line therapy is TAM and AI, respectively. Medroxyprogesterone acetate (MPA) should be used as the third-line agent, irrespective of menopausal status. However, efficacy of combinations such as LH-RH agonist plus TAM for premenopausal women and TAM plus AI for the postmenopausals is still uncertain. Patients with rapidly progressing and/or endocrine-resistant tumor should be treated with anthracycline containing regimen such as CAF (cyclophosphamide, adriamycin, 5-fluorouracil). As for the palliative modality, chemotherapy (CAF, doxifluidine) combined with MPA has resulted in improved QOL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Inhibition of progression to androgen-independence by combined adjuvant treatment with antisense BCL-XL and antisense Bcl-2 oligonucleotides plus taxol after castration in the Shionogi tumor model.

We have reported that antisense Bcl-2 oligodeoxynucleotide (ODN) delays progression to androgen independence in the androgen-dependent (AD) mouse Shionogi tumor model. Here, we characterize changes in bcl-xL, another important anti-apoptotic gene, and test the efficacy of adjuvant antisense Bcl-xL ODN therapy either alone or in combination with antisense Bcl-2 ODN and chemotherapy after castration in the Shionogi tumor model. Bcl-xL mRNA levels increased up to 3-fold postcastration and remained 1. 5-fold higher in androgen-independent (AI) recurrent tumors compared with AD tumors before castration. Treatment of Shionogi cells with antisense Bcl-xL ODN inhibited Bcl-xL expression in a dose-dependent and sequence-specific manner. Systemic administration of antisense Bcl-xL ODN in mice bearing Shionogi tumors after castration delayed emergence of AI recurrent tumors. We then examined whether combined adjuvant antisense Bcl-xL and/or Bcl-2 ODNs plus taxol (paclitaxel) therapy further delays time to AI progression. Combined treatment of Shionogi cells with antisense Bcl-xL and Bcl-2 ODNs significantly enhanced taxol chemosensitivity compared with either agent alone, reducing the IC(50) of taxol by more than 1 log. Apoptotic DNA laddering and cleavage of poly(ADP-ribose) polymerase were more substantial after treatment with combined antisense Bcl-2 and Bcl-xL ODNs plus taxol than that with either 2 agents. Adjuvant administration of antisense Bcl-xL and Bcl-2 ODNs plus micellar taxol resulted in a significantly delayed time to AI recurrence compared with administration of either 2 agents. Our findings suggest that Bcl-xL represents a suitable molecular target for antisense ODN strategy and illustrate the potential additive effects of multi-target pharmacology for cancer therapy.

Androgens↗
PubMed2004

Structural changes in cerebral arteries following nitric oxide deprivation: a comparison between normotensive and hypertensive rats.

Chronic inhibition of nitric oxide (NO) synthesis with N(omega)-nitro-L-arginine methyl ester (L-NAME) has become a model of hypertension. The purpose of this study was to evaluate the morphological changes of cerebral arteries in rats with genetic hypertension and hypertension induced by chronic NO deprivation. Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto strain (WKY) were given L-NAME (1 mg.ml(-1)) from age 5 to 7 or 9 weeks. We assessed vascular remodelling and arteriolar injury score (AIS) in various cerebral arteries using different immunohistochemical staining techniques. In WKY and SHR, L-NAME caused an elevation in tail cuff pressure (TCP). The increase in TCP was larger in SHR than in WKY. L-NAME decreased body weight, but increased heart weight in SHR. The lumen diameter and media cross-section area of internal carotid artery (ICA) in SHR were smaller than those in WKY, and further reduced in SHR and WKY after L-NAME treatment. These findings indicate that cerebral vascular remodelling occurs following chronic hypertension either from genetic origin or NO deprivation. L-NAME increased the media thickness in SHR, but not in WKY. This agent also caused an increase in cell volume density, AIS, and inflammatory cells infiltration in perivascular space with a negative growth index in ICA. The media/lumen ratio was higher in SHR than WKY, and further increased following L-NAME treatment. Diversified vascular remodelling occurred in hypertensive rats, but not in untreated WKY. In summary, these results suggest that NO deprivation and genetic hypertension cause vascular changes in various cerebral arteries.

Animals↗
PubMed1987

Hypoxia does not alter angiotensin converting enzyme activity in hamster pulmonary microvessels.

Studies were initiated to investigate the effects of hypoxia on the conversion of angiotensin I (AI) to angiotensin II (AII) in microvessels of the lung. Using the technique of allografting neonatal lung tissue into the cheek pouch of normal hamsters, the microvessels of the lung, pulmonary arterioles, and venules could be visualized and manipulated by direct in vivo microscopy. The microvessels of the lung were studied 7-10 days after allografting by anesthetizing the hamster with pentobarbital (6.0 mg/100 g body weight i.p.) and then preparing the lung tissue for observation. The tissue was suffused with a Ringer's bicarbonate solution bubbled with a normal (20% O2-5% CO2-75% N2) or a low (95% N2-5% CO2) oxygen mixture. After equilibration, a pulmonary arteriole or venule was selected for observation, and the vessel geometry was recorded. Then, a micropipette containing either AI or AII was positioned alongside the vessel, and the agent was delivered continuously for 2 minutes. Lumen diameter was recorded continually for 8-10 minutes. This procedure was repeated until both angiotensins were tested on pulmonary arterioles and venules under conditions of a normal and low oxygen environment. This protocol was repeated on cheek pouch microvessels that did not contain pulmonary allografts. Both AI and AII produced rapid decreases in the lumen diameters of all microvessels tested. This vasoconstriction was greater for AII, and the oxygen environment did not alter the response. Conversion of AI to AII was not altered by the oxygen environment, and the relative conversion was similar in the microvessels of the lung and cheek pouch.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗
PubMed1989

Apolipoprotein assays: methodological considerations and studies in non-insulin-dependent diabetes treated by diet, glibenclamide and insulin.

The effect of sample pre-treatment as a source of variability of apolipoprotein (apo) AI, AII and B assays was demonstrated with lipid dissociating agents. The average mean percentage change ranged from -58 to +133% compared with untreated samples. The apolipoprotein method selected was validated by comparing their concentrations with their corresponding lipoprotein lipid or protein in normal controls and Type 2 (non-insulin-dependent) diabetic patients. The coefficient of variation was maintained below 3.5% for apo AI, AII, B and HDL2-apo AI. The apolipoprotein concentrations of fasting plasma lipoproteins were determined in a cross-sectional study of non-obese (body-mass index less than or equal to 30) patients with Type 2 diabetes mellitus. Compared with normal subjects matched for sex, age, body-mass index, exercise, alcohol consumption and smoking. Type 2 patients at diagnosis showed reduced apo AI and HDL2-apo AI concentrations, lowered apo AI:B ratio and increased concentrations of apo B. Type 2 patients treated by diet alone (for 6-72 months) and diet plus glibenclamide (2.5-15 mg/day for 6-48 months) exhibited similar abnormalities of plasma apolipoprotein concentration to Type 2 patients at diagnosis. However, in Type 2 patients treated with insulin (25-65 U/day for 8-144 months) concentrations of apo AI and HDL2-apo AI, and the apo AI:B ratio were normal. Apo B concentrations were generally lower compared with all groups of non-insulin treated patients. These abnormalities of apolipoprotein metabolism, which are associated with premature coronary disease, are still evident in patients treated by diet and diet plus glibenclamide, but are not seen in Type 2 patients treated with insulin.

Adult↗
PubMed1995

Native like structure and stability of apo AI in a n-propanol/water solution as determined by 13C NMR.

To elucidate the molecular details of the conformation of apolipoprotein AI (apo AI), we have developed an approach related to the solubilization of this protein in 30% n-propanol. We have previously reported the promotion of a native-like structure for apo AI solubilized in n-propanol, as depicted by circular dichroism, fluorescence, and limited proteolytic digestion as compared to the lipid associated form of apo AI. In the present study, we labeled the Lys residues of apo AI with 13C by reductive methylation and used 13C NMR to confirm the formation of a native-like structure of apo AI in this environment. Furthermore, by the above criteria (circular dichroism and 13C NMR) and by using urea and temperature as denaturing agents, we show that the denaturation of the native-like structure of apo AI in n-propanol is a biphasic process. These studies show that in 30% n-propanol, apo AI contains two independently folded structural domains, of markedly different stabilities that might correspond to the amino-terminal and the carboxy-terminal halves of the molecule.

1-Propanol↗
PubMed2006

Combination therapy with aromatase inhibitors: the next era of breast cancer treatment?

Long-term endocrine therapy with either aromatase inhibitors (AIs) or tamoxifen may lead to endocrine resistance and disease progression. Recent years have seen advances in our understanding of the complex biological mechanisms associated with resistance. Growth factor signaling pathways appear to be upregulated in hormone-resistant tumours and interact with oestrogen-receptor (ER) signaling, which remains functional even after long-term endocrine deprivation. Signaling through the human epidermal and insulin-like growth-factor receptor (HER and IGFR, respectively) pathways may promote ligand-independent ER gene transcription and stimulate growth factor signaling. Therapeutic agents that inhibit these signal transduction pathways, when combined with AIs, may offer breast cancer patients new hope for more robust, longer-term remissions. Preliminary data from phase II studies of combination therapies are encouraging. There is a large programme of ongoing randomised, controlled trials, the results of which should pave the way for integrating combination therapies into clinical practice. To identify which patients will respond best to particular combinations of treatments, biomarkers and gene expression profiles are being investigated as predictors of sensitivity or resistance. In time, breast cancer treatment will become truly individualised because physicians will be able to match patients with a variety of disease phenotypes to optimal combination therapies.

Antineoplastic Agents, Hormonal↗
PubMed2006

Formulation of liposome for topical delivery of arbutin.

The aims of this study were to encapsulate arbutin (AR) in liposome to enhance the skin-whitening activity, and to investigate the effect of liposome formulation on the entrapment efficiency (EE%), skin permeation rate and skin deposition. The liposomes were prepared by a film dispersion method with several different formulations and were separated from the solution by using the gel-filtration method. The physical (size distribution, morphology) and chemical (drug entrapment efficiency, hairless mouse skin permeation and deposition) properties of liposomes were characterized. The entrapment efficiency in all liposome formulations varied between 4.35% and 17.63%, and was dependent on the lipid content. The particle sizes of liposomes were in the range of 179.9-212.8 nm in all liposome formulations. Although the permeation rate of AR in the liposome formulations decreased compared with AR solution, the deposition amount of AR in the epidermis/dermis layers increased in AR liposomal formulation. These results suggest that liposomal formulation could enhance the skin deposition of hydrophilic skin-whitening agents, thereby enhancing their activities.

Administration, Topical↗
PubMed2002

The impact of hormonal treatments on quality of life of patients with metastatic breast cancer.

BACKGROUND: The concept of quality of life (QOL) increasingly has been used to assess health-related outcomes associated with a specific disease or its treatment, especially in patients with incurable tumors, such as metastatic breast cancer (MBC). Hormonal therapy (HT) is often used to treat hormone receptor-positive MBC, with the primary treatment goal of reducing both disease burden and patient suffering. OBJECTIVE: This article reviews the instruments used to assess QOL in patients with breast cancer, the adverse effects of HTs, and the clinical trials that assess QOL in patients with MBC receiving various HTs. METHODS: Articles were identified for inclusion in this manuscript through the following searches, limited to English-language publications: MEDLINE (mid 1960s to January 2002), American Society of Oncology abstracts (1997-2001), and San Antonio Breast Cancer Symposium abstacts (2001 and 2002). The following search terms were used: quality of life, breast cancer, hormonal therapies, tamoxifen, toremifene, letrozole, anastrozole, exemestane, and megestrol acetate. CONCLUSIONS: QOL assessment following MBC treatment has become an important indicator of treatment effectiveness, and numerous clinical trials have studied the impact of HT on QOL. In general, the older HTs, such as the progestins and selective estrogen receptor modulators (SERMs), produce more adverse effects than do the newer HTs, such as the aromatase inhibitors (AIs) and estrogen receptor (ER) antagonists. QOL data regarding tamoxifen, a SERM associated with a high incidence of vasomotor symptoms and vaginal discharge, are limited, although tamoxifen has not been associated with significant psychological distress when administered as a chemopreventive or adjuvant MBC therapy in clinical trials. QOL studies comparing the third-generation AIs with tamoxifen or megestrol acetate show that the AIs produce a more favorable QOL, probably because these agents target the aromatase enzyme, which results in a lower incidence of thromboembolism and vaginal bleeding. Although QOL studies of the ER antagonist fulvestrant have not been conducted, several attributes of this new HT may contribute to the retention of a good QOL in patients with MBC. A variety of QOL-assessment tools to measure the impact of HTs on patients with MBC are available. Clinical trial data regarding QOL in patients with MBC receiving HT will be useful for both clinicians and patients in evaluating treatment options and developing treatment strategies.

Antineoplastic Agents, Hormonal↗
PubMed2001

Niacin, but not gemfibrozil, selectively increases LP-AI, a cardioprotective subfraction of HDL, in patients with low HDL cholesterol.

Evidence indicates that the high density lipoprotein (HDL) subfraction containing apolipoprotein A-I without apolipoprotein AII (LP-AI) is more antiatherogenic than HDL particles containing apolipoprotein A-I and apolipoprotein A-II (LP-AI+AII). This study examined the effect of extended-release niacin (niacin-ER) and gemfibrozil on LP-AI and LP-AI+AII particles in patients with low levels of HDL cholesterol (HDL-C). Mechanisms by which these agents modulate HDL particles were investigated by in vitro studies using human hepatoblastoma (Hep G2) cells. A total of 139 patients with low HDL-C (</=40 mg/dL) were randomized to niacin-ER or gemfibrozil in a multicenter double-blind trial. Patients were dose-escalated with once-nightly niacin-ER (1 to 2 g) or gemfibrozil (1.2 g) for 19 weeks. Niacin-ER had a greater effect in raising HDL-C and apolipoprotein A-I levels than did gemfibrozil. Niacin-ER at 1- and 2-g doses increased LP-AI levels by 8.7+/-4.0% (P=0.033) and 24.0+/-4.4% (P<0.001), respectively. Gemfibrozil had no consistent effect on LP-AI levels. LP-AI+AII levels increased 5% to 8% by both agents. In vitro studies showed that niacin, but not gemfibrozil, selectively decreased the uptake of (125)I-labeled LP-AI holoparticles by Hep G2 cells. The uptake of [(3)H]cholesterol ester was approximately 75% greater from LP-AI versus LP-AI+AII particles, but neither niacin nor gemfibrozil affected cholesterol ester uptake. These data indicate that unlike gemfibrozil, niacin selectively increases LP-AI compared with LP-AI+AII particle concentration in patients with low HDL-C levels. The mechanism of action of increased LP-AI concentration appears to be mediated by decreased hepatic removal of LP-AI particles, which are more efficient in reverse cholesterol transport, thus suggesting an additional mechanism by which niacin mediates its antiatherogenic properties.

Apolipoprotein A-I↗
PubMed2005

Systemic administration of attenuated Salmonella choleraesuis in combination with cisplatin for cancer therapy.

Some anaerobic and facultative anaerobic bacteria have been employed as anticancer agents. Previously, we have demonstrated tumor-targeting and antitumor activities of attenuated Salmonella choleraesuis carrying antiangiogenic genes. Here we exploited S. choleraesuis as a single-agent therapy and as part of a combination therapy with low-dose cisplatin for syngeneic murine lung tumor and hepatoma. Systemically injected S. choleraesuis preferentially accumulated within tumors for at least 4 weeks and the bacteria accumulated preferentially in not only subcutaneous but also orthotopic tumors over livers and spleens at ratios ranging from 1000:1 to 100,000:1. S. choleraesuis was capable of delaying tumor growth and enhancing survival in both subcutaneous tumor and experimental metastasis models. More strikingly, the combination of S. choleraesuis plus cisplatin acted additively to retard tumor growth and extensively prolong the survival time of the mice bearing hepatomas or lung tumors. Such combination treatment also increased infiltrating neutrophils and CD8+ T cells, as well as apoptotic cells, in the tumors, compared with S. choleraesuis or cisplatin treatment alone. These findings suggest that S. choleraesuis in combination with cisplatin, which exerts oncolytic effects and enhances antitumor immune responses, represents a promising strategy for the treatment of primary and metastatic tumors.

Animals↗
PubMed2004

Infragenual cuff-compression reduces venous contamination in contrast-enhanced MR angiography of the calf.

PURPOSE: To reduce venous contamination at the calf level in three-dimensional contrast-enhanced MR angiography (CE-MRA) by applying continuous infragenual cuff-compression. MATERIALS AND METHODS: Ten patients with clinically relevant peripheral arterial occlusive disease (PAOD) underwent dynamic three-dimensional CE-MRA of the calf. Six consecutive measurements were acquired with the first measurement serving as mask. Cuff-compression of 50 mmHg was attached below the knee. To allow intra-individual comparison, compression was applied unilaterally. The cuff was inflated three minutes before scanning and was continued throughout the MRA session. Venous contamination and arterial visualization scores were ranked using a five-point rating scale. Contrast-to-noise ratios (CNRs) of superficial enhancing calf-veins on the uncompressed and compressed calf sides were evaluated. An asymmetry index (AI) defined by CNR(mean) (uncompressed)/CNR(mean) (compressed) was introduced to describe the ratio in venous contrast agent supply between both sides quantitatively. RESULTS: Three-dimensional CE-MRA of the calves demonstrated significantly lower superficial venous contamination scores (P < 0.004) and clearly improved arterial visualization (P < 0.009) on the compressed side. Additionally, AI values were larger than 1 (P < 0.02), indicating a higher contrast agent supply in the superficial veins on the uncompressed side. CONCLUSION: Infragenual cuff-compression minimizes venous overlay in three-dimensional CE-MRA at calf level by reduction of contrast agent supply in the superficial veins.

Aged↗
PubMed1988

Alteration of fate of vasoactive autacoids in pulmonary circulation following monocrotaline-induced lung vascular injury in rats.

1. To learn how pulmonary vascular injury alters the ability of the lung to metabolize vasoactive autacoids, lung vascular lesions were produced in rats by a single subcutaneous injection of monocrotaline (90 mg kg-1), and the blood pressure responses to angiotensin I (AI), angiotensin II (AII), bradykinin, prostaglandin E2 (PGE2) and substance P were examined. Vasoactive agents were given intravenously or intra-arterially. 2. On histological examination of the lung at 3 weeks after monocrotaline treatment, degeneration or necrotization of endothelial cells was evident. 3. The conversion of AI to AII was only slightly depressed by monocrotaline treatment. On the other hand, the depressor response to intravenously injected bradykinin was enhanced in monocrotaline-treated rats. When the rats were pretreated with indomethacin the depressor response to intravenous bradykinin was the same for both control and monocrotaline-treated groups which suggests that endogenous prostaglandins are involved in the enhancement of the response to bradykinin. 4. In monocrotaline-treated rats the depressor response to intravenous PGE2 was significantly enhanced depending on the period following the treatment, while that to the intra-arterial injection did not differ from control. 5. The data suggest that monocrotaline-induced lung injury impairs the metabolism of PGE2 during pulmonary circulation but has little effect on the conversion of AI to AII and the degradation of bradykinin in rats.

Angiotensin I↗