Biomedical subjects

M Lin

Publications and source records attributed to M Lin.

At least 217 records · Page 12Linked to original sources

PubMed1996

Mild hypoxia induces hypertrophy of cultured neonatal rat cardiomyocytes: a possible endogenous endothelin-1-mediated mechanism.

Hypoxic or ischemic stresses on cardiomyocytes may cause a variety of compensatory responses including cell hypertrophy. In this study, we examined whether hypoxia induces hypertrophy of cardiomyocytes in vitro and whether hypoxia-induced hypertrophy is inhibited by an endothelin A receptor antagonist (BQ123). Neonatal rat cardiomyocytes were cultured in 10% O2/85% N2/5% CO2 or 95% N2/5% CO2 to produce a mild or severe hypoxic condition, respectively. Cardiomyocytes exposed to severe hypoxia revealed degenerative morphological changes and a decrease of cell number, suggesting the toxicity of severe hypoxia on cardiomyocytes. In contrast, cardiomyocytes with mild hypoxia developed hypertrophy; cell surface area of cardiomyocytes as evaluated by an image analyser system increased by 1.6-fold over control after 48 h. [3H]leucine incorporation into the cells was significantly increased by mild hypoxia but decreased by severe hypoxia, mRNA level of skeletal alpha-actin, a genetic marker of cardiac hypertrophy, up-regulated after 6-24 h by mild hypoxia. A transient increase of preproET-1 mRNA and a time-dependent increase of ET-1 protein in the culture medium were also observed in cardiomyocytes exposed to mild hypoxia. BQ123 partially inhibited either hypoxia-induced [3H]leucine incorporation or skeletal alpha-actin mRNA in a dose-dependent manner. These data suggest that mild hypoxia induces hypertrophy of cardiomyocytes and that activation of endogenous ET-1 may, at least in part, mediate this hypertrophic responses as an autocrine/ paracrine factor.

Actins↗

PubMed1996

Protective effects of garlic and related organosulfur compounds on acetaminophen-induced hepatotoxicity in mice.

In previous studies, we have demonstrated that diallyl sulfide, a flavor component of garlic, protects against chemically induced hepatotoxicity. The present study examined the activities of fresh garlic homogenates (FGH) and related organosulfur compounds in the protection against acetaminophen (APAP)-induced hepatotoxicity and the possible mechanisms involved in this protection. When FGH (5 g/kg) was administered to Swiss-Webster mice 2 hr prior to, or immediately after, an APAP treatment (0.2 g/kg), APAP-induced hepatotoxicity was essentially prevented as indicated by serum levels of alanine aminotransferase and lactate dehydrogenase and by liver histopathology. Partial protection was observed with a lower dose of FGH (0.5 g/kg). FGH also prevented APAP-induced hepatic glutathione depletion in a dose-dependent manner. FGH significantly inhibited the formation of APAP-oxidized metabolites, as indicated by decreased plasma levels of oxidized APAP metabolites. The amount of APAP excreted as oxidized metabolites in the 24 hr urine samples was also significantly lower in the mice pretreated with FGH. FGH supernatant inhibited cytochrome P450-dependent APAP oxidation in microsomal incubations. The results suggest that the protection against APAP-induced hepatotoxicity by FGH is mainly due to its inhibition of P450-mediated APAP bioactivation. Several garlic-derived organosulfur compounds and structurally related compounds were examined for their abilities to protect against APAP-induced hepatotoxicity. An S-allyl structure appears to be a common feature for most sulfides to inhibit P450 2E1-dependent activity and to display good protective activities.

Acetaminophen↗

PubMed1996

Molecular comparison of cultured hybridoma cells that switch isotypes at high and low rates.

We have previously reported the isolation of variants from the 36.65 and PC1.4.1 hybridoma cell lines that spontaneously switch from gamma 1 to gamma 2a and gamma 2b at high and low rates. In order to further characterize the phenotype of these variants, we have now investigated the production of germline transcripts and methylation which are two of the molecular correlates of isotype switching. While some of the correlations that exist in normal cells were present in some of the clonal variants, others were not. However, the higher switching variants of both cells lines had higher recombinational activity as measured with a shuttle vector. The distinct phenotypic characteristics of each cell line provide an opportunity to dissect the roles of individual molecular events in the process of isotype switching.

Animals↗

PubMed1996

When to discharge patients with bleeding peptic ulcers: a prospective study of residual risk of rebleeding.

BACKGROUND: From January 1993 to December 1994, we conducted a prospective study to investigate the evolutionary change of rebleeding risk in bleeding peptic ulcers. To obviate possible confounding factors that would influence decision making for discharge of patients, subjects with coexistent acute illnesses, systemic bleeding disorders, alcoholism, and use of nonsteroidal anti-inflammatory drugs were excluded. METHODS: Emergency endoscopies were performed in patients with hematemesis or a melena within 24 hours of admission. Ulcer lesions were divided into six categories according to endoscopic findings. The residual risks of rebleeding of each type of ulcers were calculated for 10 days, and the critical point of acceptable rebleeding risk after discharge was set at 3%. RESULTS: Three hundred ninety-two patients with bleeding peptic ulcers completed the study. The ulcers, characterized by clean bases, red or black spots, adherent clots, nonbleeding visible vessels without local therapy, nonbleeding visible vessels with local therapy, and bleeding visible vessels with local therapy took 0, 3, 3, 4, 4, and 3 days, respectively, to decrease rebleeding risk to below the critical point. All episodes of fatal rebleeding (n = 4) occurred within 24 hours after admission. CONCLUSIONS: Patients with clean-based ulcers can be discharged in the first day of admission. The optimal duration required for hospitalization of patients with ulcers characterized by nonbleeding visible vessels at initial endoscopy is 4 days. The remaining patients with ulcers marked by other bleeding stigmata may be discharged after a 3-day observation.

Adolescent↗

PubMed1996

Protective effects of diallyl sulfide on acetaminophen-induced toxicities.

Diallyl sulfide (DAS), a major flavour component of garlic, is known to modulate drug metabolism and may protect animals from chemically induced toxicity and carcinogenesis. In this study the effects of DAS on the oxidative metabolism and hepatotoxicity induced by acetaminophen (APAP) in rats were investigated. In the hepatotoxicity evaluation of Fischer 344 rats there was a dose-dependent increase in the odds of mortality rate by APAP (P = 0.009); DAS treatment significantly protected rats from APAP-related mortality (P = 0.026). Liver toxicity determined by lactate dehydrogenase activity was significantly increased by APAP treatment (0.75 g/kg). Pretreatment with DAS protected animals from APAP-induced liver toxicity in a time- and dose-dependent fashion. Treatment of DAS (50 mg/kg) 3 hr after APAP dosing significantly (P < 0.05) protected rats from APAP-induced liver toxicity. The metabolism of APAP (50 microM) in vitro was significantly inhibited by DAS (0.3-1 mM) in liver microsomes isolated from F344 rats. As the effect of DAS on APAP-induced hepatotoxicity in vivo was observed only when DAS was administered before or shortly after (< 3 hr) APAP dosing, data suggested that the protective effect of DAS is mainly at the metabolic activation step of APAP. However, the possibility that DAS may also have effects on other drug metabolism systems, such as glutathione (GSH) and glutathione S-transferases, cannot be ruled out.

Acetaminophen↗

PubMed1996

Benzodiazepine receptor ligands with different intrinsic efficacies alter ethanol intake in alcohol-nonpreferring (NP) rats.

Benzodiazepine (BDZ) receptor ligands with varying intrinsic efficacies [RO19-4603, 0.02-0.15 mg/kg; FG 7142 1-16 mg/kg; DMCM, 1-8 mg/kg; RO16-6028 (bretazenil), 8-32 mg/kg] in modulating GABAergic activity were examined for the ability to alter palatability-induced ethanol (EtOH) intake in the alcohol-nonpreferring (NP) line of rats. NP rats on a 22-hour fluid-deprivation schedule were given 2-hour daily access to a 10% (v/v) EtOH/3% (g/v) polycose solution and water. Average EtOH intake was 2.1 +/- 0.2 g/kg/2 hours, and water intake was 17.1 +/- 0.9 ml/2 hours. During the initial 15 minutes of the 2-hour session, RO19-4603, the imidazothienodiazepine partial inverse agonist reduced EtOH intake to 19% of control values at 0.04 mg/kg and completely suppressed drinking of the EtOH solution at 0.15 mg/kg. Twenty-four-hour postdrug administration, the 0.08-mg/kg dose of RO19-4603 completely suppressed drinking of the EtOH solution at the 60-minute interval, and the 0.15-mg/kg dose reduced intake to 20% of control levels at the 15-minute interval. FG 7142, the partial beta-carboline inverse agonist reduced EtOH drinking at the 60-minute interval with the 1-mg/kg dose, and the 16-mg/kg dose reduced water intake at the 15-minute interval. DMCM, the full beta-carboline inverse agonist, significantly reduced water intake at 15 minutes (4 and 8 mg/kg), and the same doses caused a substantial increase in EtOH drinking at the 120-minute interval. The anxiolytic agent bretazenil (16 and 32 mg/kg) increased EtOH consumption during the initial 15 minutes to 270% to 425% of control levels, and water intake increased by the end of the 2-hour session to as much as 210% of control following administration of the 32-mg/kg dose. These findings support existing evidence suggesting that BDZ receptor ligands may modify neuronal processes that mediate some reinforcing and/or aversive properties of alcohol. They further demonstrate a potential importance of the GABAA-BDZ receptor complex in mediating palatability- (environmentally) induced EtOH drinking even in rats selectively bred for low alcohol preference.

Analysis of Variance↗

PubMed1996

The distribution of the MiIII (Gp.Mur) phenotype among the population of Taiwan.

The MiIII (Gp.Mur) phenotype is rare among Caucasians but has a much higher incidence among some Oriental populations. In Taiwan the population is relatively heterogenous and, as expected, the incidence of the MiIII phenotype was found to vary markedly among the different ethnic groups. The highest frequencies of the MiIII phenotype were found among some of the indigenous groups, namely the Ami, Yami and Puyuma groups, being 88.4%, 34.3% and 21.2%, respectively, which are also the highest frequencies among any population group reported so far. Antibody screening cells and antibody identification panels containing the MiIII phenotype can obviously be obtained very easily from Ami blood donors and compatible blood for patients with anti-"Mia' can most easily be obtained from Chinese blood donors, except those living on the east coast.

Asian People↗

PubMed1996

Induction of antibodies to the bluetongue virus core polypeptide VP7 in sheep by internal image rabbit antiidiotypic antibodies.

We previously generated rabbit polyclonal antiidiotypic antibody (anti-Id) to a murine monoclonal antibody (M1875) specific for the bluetongue virus core protein VP7, and demonstrated that this anti-Id (designated RAb2-A) had the characteristics of an internal image anti-Id (Ab2 beta). In this communication, RAb2-A was used to induce immune responses in sheep and the responses were compared to immunization with VP7. The immune sera were tested for the presence of anti-VP7 antibodies and the expression of the Id of M1875. Animals immunized with RAb2-A were able to produce M1875-like antibody responses, i.e., they recognized the same or a similar epitope as M1875 and possessed the M1875 Id, without subsequent exposure to the original antigen. This was demonstrated by showing that antibodies induced by RAb2-A (i) reacted specifically with the immunizing anti-Id, (ii) were capable of binding VP7, (iii) inhibited M1875 from binding to VP7, and (iv) inhibited M1875 from binding to RAb2-A. Animals immunized with purified VP7 produced antibodies that possessed the epitope and idiotope specificity of M1875. No antibody responses to VP7 were detected in control animals immunized with either rabbit anti-Id to the pseudorabies virus glycoprotein gII or BHK-21 cell proteins. We conclude that rabbit anti-Id RAb2-A serologically mimics an M1875-defined VP7 epitope sufficiently to function as a surrogate antigen for inducing anti-bluetongue virus VP7 responses.

Animals↗

PubMed1996

Dantrolene sodium can increase or attenuate activity of skeletal muscle ryanodine receptor calcium release channel. Clinical implications.

BACKGROUND: Dantrolene sodium (DS) is a direct-acting skeletal muscle relaxant whose only known action is to block calcium release from intracellular storage sites. The exact site of action for DS is unknown, but its efficacy in treating and preventing anesthetic-induced malignant hyperthermia (MH) is well established. METHODS: Single ryanodine (Ry1) receptor calcium release channels were incorporated into a planar lipid bilayer for electrophysiologic recording and for subsequent analysis of the channel's gating and conductance properties. The cellular effects of low DS concentrations were investigated by isometric contracture tension responses in biopsied MH human and dog muscle fascicles and in normal, single fibers from human vastus lateralis muscle. RESULTS: Two concentration-dependent DS effects on the isolated Ry1 receptor were discovered, suggesting at least two different binding sites. At nanomolar concentrations, DS activated the channel by causing three-to fivefold increases in open-state probability and dwell times. At micromolar concentrations, DS first increased then reduced activity in the channels; with the dominant effect being reduced activity. A 20 nm concentration of DS produced significant contracture tension in human muscle from one MH subject and caused potentiation of twitch in muscle from another MH patient. Halothane contracture in MH dog muscle was followed by an additional increase in tension when treated with 20 nm DS. Other investigations on chemically skinned, human fibers showed that calcium loaded in the sarcoplasmic reticulum was partially released by nM DS. CONCLUSIONS: The study results suggest that at least two binding sites for DS exist on the Ry1 receptor calcium channel. A low-affinity (microM) site is associated with reduced channel gating and open-state dwell time and may relate to the established pharmacologic muscle relaxant effect of DS. The proposed high-affinity (nM) DS binding site activates the channel, producing Ca2+ release to the myoplasm, which, under environmentally adverse conditions, could damage genetically predisposed MH muscle. Such a phenomenon, if it occurs in DS treated MH patients, could generate a recrudescence of the syndrome.

Animals↗

PubMed1996

The JHM strain of mouse hepatitis virus induces a spike protein-specific Db-restricted cytotoxic T cell response.

Cytotoxic T lymphocyte (CTL) activity specific for mouse hepatitis virus (MHV) JHM strain (JHMV or MHV-4) was examined using in vitro stimulated spleen cells derived from immunized C57BL/6 (H-2b) mice. Target cells infected with JHMV were specifically recognized; however, analysis of target cells expressing the virus structural proteins via recombinant vaccinia viruses showed no recognition of the viral nucleocapsid (N), membrane (M), small membrane (sM) or haemagglutinin-esterase (HE) proteins. Only target cells expressing the virus spike (S) protein were recognized. Furthermore, the majority of CTL activity was restricted to target cells expressing the MHC class I Db molecules. Analysis of truncations and deletions of the S protein expressed by recombinant vaccinia viruses and peptide coated targets identified a single antigenic epitope, aa 510-518, conforming to the Db binding motif. These amino acids are contained within a domain deleted from a number of strains of mouse hepatitis virus, suggesting a role for immune pressure. To determine the potential for CTL specific for an epitope(s) within a non-structural protein, 24 CTL lines were established and characterized. No evidence for the induction of non-specific CTL activity or virus-specific CTL restricted to an epitope in a non-structural protein was obtained. These data indicate that the predominant CTL activity in JHMV-infected C57BL/6 mice is Db restricted and specific for a single epitope contained within aa 510-518 of the S protein.

Amino Acid Sequence↗

PubMed1996

Biological mimicry of the bluetongue virus core protein VP7 by rabbit anti-idiotype.

A subpopulation of rabbit polyclonal anti-idiotypic antibody (anti-Id) was previously produced to a murine monoclonal antibody (mAb) (M1875) specific for the bluetongue virus core protein VP7. In this report, mimicry of VP7 by this anti-Id (designated RAb2-A) was functionally analyzed through immunization of Balb/c mice with RAb2-A or purified VP7. Animals immunized with RAb2-A were able to produce an M1875-like Ab3 antibody response with idiotype and epitope specificity resembling that of M1875 without subsequent exposure to the nominal antigen. This conclusion was supported by experiments showing that the RAb2-A-induced Ab3 antibodies (i) reacted specifically with the immunizing anti-Id; (ii) were capable of binding VP7; (iii) inhibited M1875 from binding to VP7; and (iv) inhibited M1875 from binding to RAb2-A. Similarly, mice immunized with purified VP7 also produced antibodies that exhibited characteristics such as idiotype and epitope specificity in common with M1875. No antibody response to VP7 was detected in control groups of mice immunized with either normal rabbit IgG or BHK-21 cell components. Therefore, it can be concluded that rabbit anti-Id RAb-2-A mimics an M1875-defined VP7 epitope sufficiently to function as a surrogate antigen for inducing an anti-bluetongue virus response.

Animals↗

PubMed1996

Evidence that two distinct populations of rabbit anti-idiotypic antibodies are induced by three monoclonal antibodies specific for bluetongue virus core protein VP7.

Three groups of anti-idiotypic antibodies (anti-Id or Ab2), designated RAb2-A, RAb2-B1, and RAb2-B2, were isolated from rabbit antiserum raised against three monoclonal antibodies (mAbs) (M1875, M1877, and M1886) specific for the bluetongue virus core protein, VP7. RAb2-A was specific for the idiotype of M1875. RAb2-B1 and RAb2-B2, isolated through the M1877 and M1886 affinity columns, respectively, were directed against the common idiotype that is shared by M1877 and M1886 and therefore classified in the same population (RAb2-B). Further characterization revealed that the two anti-Id populations, RAb2-A and RAb2-B, were significantly different. RAb2-A was an Ab2 beta type of anti-Id since (i) its reaction with M1875 was inhibited by the antigen; (ii) it inhibited the M1875-VP7 interaction; and (iii) it elicited anti-VP7 antibody response in Balb/c mice. In contrast, RAb2-B may represent an Ab2 alpha type of anti-Id since its reactions with M1877 or M1886 were not inhibited by the antigen, even though it inhibited mAbs from binding to the antigen. These results indicated that RAb2-A and RAb2-B represent two distinct populations of anti-Ids to anti-VP7 mAbs with similar epitope specificity.

Animals↗

PubMed1996

Comparison of the Lewis phenotypes among the different population groups of Taiwan.

In Caucasians, three red cell Lewis phenotypes are observed, namely Le (a+b-), Le (a-b+) and Le (a-b-). For Chinese living in Taiwan the Le (a+b-) phenotype is replaced by the Le (a+b+) phenotype so that the three red cell Lewis phenotypes observed in Chinese are Le (a+b+), Le (a-b+) and Le (a-b-). In addition, Chinese individuals with Le (a-b-) red cells can be subdivided into two groups, namely those who secrete both ABH and Lewis substances in saliva and those who secrete only ABH substances in saliva. However, four red cell Lewis phenotypes Le (a+b-), Le (a+b+), Le (a-b+) and Le (a-b-) are observed among some of the indigenous groups living in Taiwan. Red cell Le (a+b-) individuals among these indigenous groups can also be subdivided into at least two groups, namely those with Le(a) and Le(b) in saliva (plus varying amounts of ABH substances) and those with just Le(a) in saliva. The former are most likely a weak form of the red cell Le (a+b+) phenotype while the latter appear to be similar to the Caucasian red cell Le (a+b-) phenotype. There was also one red cell Le (a+b-) individual whose saliva had a small amount of A substance as well as Lea substance and therefore appeared to be intermediate between the above two forms of the Le (a+b-) phenotype.

Asian People↗

PubMed1996

Synthesis and conformational analysis of cyclic pentapeptide endothelin antagonists.

Two endothelin antagonists cyclo(D-Leu-D-Val-Pro-D-Asp-Trp) (IPI-147), and cyclo (D-Trp-D-Asp-Ac3c-D-Val-Leu) (IPI-725) have been synthetized. Their solution conformations have been studied in aqueous solution by NMR spectroscopy and dynamics simulation. Activity studies show that IPI-725 is a strong ETA antagonist, while IPI-147 is a weak ETA antagonist. Comparison of the solution conformations of these two ETA antagonists suggests that the difference in their activities results from their structural differences. IPI-147 contains a type II beta-turn with a hydrogen bond between NH of D-Val and the C = O of D-Asp. IPI-725, on the other hand, contains two turns, a type II beta-turn with a hydrogen bond between NH of D-Asp and C = O of D-Val, as well as a gamma'-turn with a hydrogen bond formed between D-Val NH and D-Asp carbonyl group. Therefore IPI-147 appears to be more flexible than IPI-725. Although both beta-turns contain the same residues, their orders in the turn are reversed. The beta-turn in IPI-725 is formed with D-Val:Leu:D-Trp:D-Asp, while in IPI-147, the beta-turn is formed with D-Asp:Trp:D-Leu:D-Val. The activities and solution conformations of IPI-147 and IPI-725 were also compared with BQ-123 [cyclo(D-Trp-D-Asp-Pro-D-Val-Leu)], a well characterized, highly potent endothelin antagonist.

Endothelins↗

PubMed1996

Modification of the Mycobacterium bovis extracellular protein MPB70 with fluorescein for rapid detection of specific serum antibodies by fluorescence polarization.

The principle of fluorescence polarization described by Perrin (F. Perrin, J. Phys. Radium 7:390-401, 1926) was applied to the development of a novel assay that used fluorescein-labeled Mycobacterium bovis secretory protein MPB70 for rapid detection of anti-MPB70 antibodies in selected sera from three M. bovis-infected species (elk, Ilama, and bison). Labeling of purified MPB70 with fluorescein isothiocyanate resulted in the incorporation of 0.96 +/- 0.08 (mean +/- standard deviation; n = 3) fluorescein group per MPB70 molecule. The labeled protein fluoresced strongly with an emission maximum at 518 nm when excited with light of a wavelength near 493 nm, and its immunoreactivity with anti-MPB70 monoclonal antibody 4C3/17 was not altered by modification with fluorescein. The fluorescence polarization assay protocol was optimized for analysis of serum samples by incorporating into the assay buffer 0.05% lithium dodecyl sulfate, which prevents the occurrence of some nonspecific interactions. Sera from M. bovis-infected animals, selected on the basis of exhibiting the presence of anti-MPB70 antibodies, as detected by enzyme-linked immunosorbent assay (ELISA), reacted with fluorescein-labeled MPB70, resulting in an increase in polarization of up to 330 milli-polarization units, in contrast to the values for noninfected sera (167 to 178 mP), which were close to that obtained in the absence of specific antibodies (164.7 +/- 3.3 mP; n = 6). These results demonstrated the feasibility of using fluorescein-labeled MPB70 to detect anti-MPB70 antibodies by fluorescence polarization and suggested that the assay described here can be an alternative to ELISA or other antibody assay systems. The advantages of this original methodology and its general applicability to the diagnosis of infectious diseases are discussed.

Animals↗

PubMed1996

Selective IgA deficiency and anaphylactoid transfusion reaction: a case report.

Anaphylactoid transfusion reaction following the administration of incompatible blood products can be life threatening, but accounts for only a very small proportion of all transfusion reactions. One of the causes of anaphylactoid transfusion reaction is the reaction of patient's anti-immunoglobulin A(IgA) with plasma IgA which is usually present in transfused blood. We report a case who had anaphylactoid transfusion reactions after transfusion of only a few milliliters of packed RBC from 3 consecutive donors, in spite of compatible pretransfusion crossmatches. The patient's serum revealed IgA deficiency accompanied by high-titer anti-IgA. The family study showed that one of her sons had partial IgA deficiency accompanied by anti-IgA2. In conclusion, although selective IgA deficiency is rare in Taiwan, it may still occasionally result in severe anaphylactoid transfusion reactions.

Aged↗

PubMed1996

Regulation of endothelial IGFBP-3 synthesis and secretion by IGF-I and TGF-beta.

We have examined the regulation of endothelial IGFBP-3 production by IGF-I and TGF-beta, two growth factors thought to play a major roles in the complications of diabetes mellitus. In addition, we developed a sensitive method for IGFBP-3 mRNA quantitation by adapting the fluorescent modification of the competitive PCR strategy. Our results using both Northern analysis and the fluorescent competitive PCR method indicate that: (1) IGFBP-3 mRNA is increased 2- to 10-fold by IGF-I and maximally reduced to 20% of control by TGF-beta; (2) the changes in mRNA levels correlate with the levels of IGFBP-3 protein secreted into the media by these cells; (3) the induction of IGFBP-3 mRNA and protein by IGF-I analogs was directly related to their ability to bind to the type I IGF receptor, reflecting an IGF-I receptor-mediated process; and (4) steady state IGFBP-3 mRNA levels did not change significantly after a 6 h incubation with actinomycin D in the presence or absence of the growth factors suggesting that the observed IGF-I/TGF-beta effects occur at the level of gene transcription rather than mRNA stability.

Adipose Tissue↗

PubMed1996

Comparisons of long-term effects of lisinopril vs nifedipine vs conventional therapy in the treatment of mild-to-moderate hypertension in patients with chronic obstructive pulmonary disease.

BACKGROUND: Any hypertensive patient may be found to have associated lung disease. The response of high blood pressure to specific antihypertensive agents in this category is still unknown. Thus, a group of 76 consecutive patients with mild-to-moderate hypertension and chronic obstructive pulmonary disease (COPD) were selected to participate in a clinical antihypertensive trial to define the roles of lisinopril, nifedipine and conventional therapy, and their impact on the renin-antiotensin system (RAS). METHODS: After a two-week placebo period, patients were randomly assigned to a regimen of one of three main treatment strategies: (A) lisinopril with or without diuretics; (B) nifedipine with or without diuretics; or (C) diuretics with or without conventional vasodilators (sorbitrate and hydralazine) or selective beta-blockers. The drug doses were titrated to a goal of less than 90 mmHg for maximal diastolic pressure, and the patients continued to receive therapy for at least one year. RESULTS: After one year of follow-up, only 66 patients had completed the study. All high blood pressure was significantly reduced by the three regimens (p < 0.005), but no significant difference in blood pressure control by any individual regimen was noted. Double product also showed the similar trend. Therapy A achieved the best reduction of double product among three regimens, but statis tieally insignificant. Furthermore therapy A suppressed the RAS, whereas therapies B and C might activate this system. Concomitantly, therapy A also had significant favorable effects on metabolic responses in contrast to therapy C. Therapy B revealed a neutral effect on such responses. CONCLUSIONS: These data indicated that these three main strategies could provide significant antihypertensive efficacy for blood pressure control in patients with hypertension and COPD. For preventive strategy, therapy A may provide more advantageous effects than therapy C. A long-term double-blind trial including more subjects is warranted to identify the true advantages of therapy A in reduction or major cardiovascular and respiratory events.

Aged↗