Neurophysiological and behavioral responses to music therapy in vegetative and minimally conscious States.

Assessment of awareness for those with disorders of consciousness is a challenging undertaking, due to the complex presentation of the population. Debate surrounds whether behavioral assessments provide greatest accuracy in diagnosis compared to neuro-imaging methods, and despite developments in both, misdiagnosis rates remain high. Music therapy may be effective in the assessment and rehabilitation with this population due to effects of musical stimuli on arousal, attention, and emotion, irrespective of verbal or motor deficits. However, an evidence base is lacking as to which procedures are most effective. To address this, a neurophysiological and behavioral study was undertaken comparing electroencephalogram (EEG), heart rate variability, respiration, and behavioral responses of 20 healthy subjects with 21 individuals in vegetative or minimally conscious states (VS or MCS). Subjects were presented with live preferred music and improvised music entrained to respiration (procedures typically used in music therapy), recordings of disliked music, white noise, and silence. ANOVA tests indicated a range of significant responses (p ≤ 0.05) across healthy subjects corresponding to arousal and attention in response to preferred music including concurrent increases in respiration rate with globally enhanced EEG power spectra responses (p = 0.05-0.0001) across frequency bandwidths. Whilst physiological responses were heterogeneous across patient cohorts, significant post hoc EEG amplitude increases for stimuli associated with preferred music were found for frontal midline theta in six VS and four MCS subjects, and frontal alpha in three VS and four MCS subjects (p = 0.05-0.0001). Furthermore, behavioral data showed a significantly increased blink rate for preferred music (p = 0.029) within the VS cohort. Two VS cases are presented with concurrent changes (p ≤ 0.05) across measures indicative of discriminatory responses to both music therapy procedures. A third MCS case study is presented highlighting how more sensitive selective attention may distinguish MCS from VS. The findings suggest that further investigation is warranted to explore the use of music therapy for prognostic indicators, and its potential to support neuroplasticity in rehabilitation programs.

Assessing pediatric anesthesia practices for volunteer medical services abroad.

BACKGROUND: Anesthetic techniques and problems in volunteer medical services abroad are different from those of either the developed countries from which volunteers originate or the host country in which they serve because of differences in patient population, facilities, and goals for elective surgery. Assessing outcomes is hampered by the transience of medical teams and the global dispersion of providers. We studied general anesthesia techniques and outcomes in a large international voluntary surgical program. METHODS: Anesthesia providers and nurses participating in care of patients undergoing reconstructive plastic and orthopedic surgery by Operation Smile over an 18-month period were asked to complete a quality assurance data record for each case. Incomplete data were supplemented by reviewing the original patient records. RESULTS: General anesthesia was used in 87.1% of the 6,037 cases reviewed. The median age was 5 yr (25th-75th percentiles: 2-9 yr). Orofacial clefts accounted for more than 80% of procedures. Halothane mask induction was performed in 85.6% of patients; 96.3% of patients had tracheal intubation, which was facilitated with a muscle relaxant in 19.3%. Respiratory complications occurred during anesthesia in 5.0% of patients and during recovery (postanesthesia care unit) in 3.3%. Arrhythmias requiring therapy occurred in 1.5%, including three patients to whom cardiopulmonary resuscitation was administered. Prolonged ventilatory support was required in seven patients. There was one death. Inadvertent extubation during surgery occurred in 38 patients. Cancellation of surgery after induction of anesthesia occurred in 25 patients. Overall, complications were more common in younger children. CONCLUSIONS: Our study showed that in this setting it is feasible to track anesthesia practice patterns and adverse perioperative events. We identified issues for further examination.

A novel sodium-hydrogen exchanger isoform-1 inhibitor, zoniporide, reduces ischemic myocardial injury in vitro and in vivo.

The cardioprotective efficacy of zoniporide (CP-597,396), a novel, potent, and selective inhibitor of the sodium-hydrogen exchanger isoform 1 (NHE-1), was evaluated both in vitro and in vivo using rabbit models of myocardial ischemia-reperfusion injury. In these models, myocardial injury was elicited with 30 min of regional ischemia and 120 min of reperfusion. Zoniporide elicited a concentration-dependent reduction in infarct size (EC(50) of 0.25 nM) in the isolated heart (Langendorff) and reduced infarct size by 83% (50 nM). This compound was 2.5- to 20-fold more potent than either eniporide or cariporide (EC(50) of 0.69 and 5.11 nM, respectively), and reduced infarct size to a greater extent than eniporide (58% reduction in infarct size). In open-chest, anesthetized rabbits, zoniporide also elicited a dose-dependent reduction in infarct size (ED(50) of 0.45 mg/kg/h) and inhibited NHE-1-mediated platelet swelling (maximum inhibition 93%). Furthermore, zoniporide did not cause any in vivo hemodynamic (mean arterial pressure, heart rate, rate pressure product) changes. Zoniporide represents a novel class of potent NHE-1 inhibitors with potential utility for providing clinical cardioprotection.

Aldose reductase inhibition alone or combined with an adenosine A(3) agonist reduces ischemic myocardial injury.

This study investigated whether aldose reductase (AR) inhibition with zopolrestat, either alone or in combination with an adenosine A(3)-receptor agonist (CB-MECA), reduced myocardial ischemic injury in rabbit hearts subjected to 30 min of regional ischemia and 120 min of reperfusion. Zopolrestat reduced infarct size by up to 61%, both in vitro (2 nM to 1 microM; EC(50) = 24 nM) and in vivo (50 mg/kg). Zopolrestat reduced myocardial sorbitol concentration (index of AR activity) by >50% (control, 15.0 +/- 2.2 nmol/g; 200 nM zopolrestat, 6.7 +/- 1.3 nmol/g). A modestly cardioprotective concentration of CB-MECA (0.2 nM) allowed a 50-fold reduction in zopolrestat concentration while providing a similar reduction in infarct size (infarct area/area at risk: control, 62 +/- 2%; 1 microM zopolrestat, 24 +/- 5%; 20 nM zopolrestat plus 0.2 nM CB-MECA, 20 +/- 4%). In conclusion, AR inhibition is cardioprotective both in vitro and in vivo. Furthermore, combining zopolrestat with an A(3) agonist allows a reduction in the zopolrestat concentration while maintaining an equivalent degree of cardioprotection.

Effects of negative life experiences on phobia onset.

BACKGROUND: Conditioning theories, stress theories and social psychological theories each suggest that negative life experiences should influence phobia onset, though the patterns of effects suggested by each type of theory are different. Few previous studies have estimated the effects of a broad enough range of life experiences on onset of multiple types of phobia to evaluate patterns of effects. METHODS: Retrospective data on life experiences and history of phobia from a representative sample of persons 15-54 years old from the US population (the National Comorbidity Survey) are analyzed using discrete-time event history methods. RESULTS: The effects of 12 negative life events and ten chronic childhood adversities on onset of agoraphobia, specific phobia, and social phobia are presented. Three discrete events have unique effects on agoraphobia onset: life threatening accidents, combat in war (for men), and a fire/flood or other natural disaster. Two chronic experiences during childhood have unique effects on specific phobia onset: violence at the hands of one or more adults, and verbal aggression between parents. Sexual assault by a relative and verbal aggression between parents have unique effects on social phobia onset. The effect of sexual assault by a relative on social phobia is confined to women, and to phobias beginning before age 12. CONCLUSIONS: Unpredictable and uncontrollable events that threaten or result in physical harm influence agoraphobia onset. Potentially predictable but difficult to control childhood experiences (e.g., chronic parental violence) influence specific phobia onset. Blame is a likely mediator of the effect of sexual abuse on social phobia. No data on perceptions of predictability and controllability of life experiences, or of blame, were available for analysis. These conclusions are therefore based on speculations about social psychological processes that have been supported by previous research and theory.

A cold shock-induced cyanobacterial RNA helicase.

The ability to modify RNA secondary structure is crucial for numerous cellular processes. We have characterized two RNA helicase genes, crhB and crhC, which are differentially expressed in the cyanobacterium Anabaena sp. strain PCC 7120. crhC transcription is limited specifically to cold shock conditions while crhB is expressed under a variety of conditions, including enhanced expression in the cold. This implies that both RNA helicases are involved in the cold acclimation process in cyanobacteria; however, they presumably perform different roles in this adaptation. Although both CrhB and CrhC belong to the DEAD box subfamily of RNA helicases, CrhC encodes a novel RNA helicase, as the highly conserved SAT motif is modified to FAT. This alteration may affect CrhC function and its association with specific RNA targets and/or accessory proteins, interactions required for cold acclimation. Primer extension and analysis of the 5' untranslated region of crhC revealed the transcriptional start site, as well as a number of putative cold shock-responsive elements. The potential role(s) performed by RNA helicases in the acclimation of cyanobacteria to cold shock is discussed.

Relative importance of adenosine A1 and A3 receptors in mediating physiological or pharmacological protection from ischemic myocardial injury in the rabbit heart.

Although ischemic preconditioning (IP) in several species can be pharmacologically mimicked by selective adenosine A1 or A3 receptor agonists, it is currently unclear which receptor subtype (A1 and/or A3) is physiologically involved in mediating IP. To investigate this question, we determined (a) the affinity of adenosine for rabbit adenosine A1 and A3 receptors, and (b) the effects of selective rabbit A1 receptor blockade on IP and adenosine-mediated cardioprotection in a rabbit Langendorff model of myocardial ischemia-reperfusion injury. Adenosine was 19-fold selective for inhibition of N6-(4-amino-3-[125I]iodobenzyl)adenosine (125I-ABA) binding to recombinant rabbit A1 v rabbit A3 receptors (A1 Ki: 28 nm; A3 Ki 532 nm). Buffer-perfused rabbit hearts were exposed to 30 min regional ischemia and 120 min of reperfusion, and infarct size was measured by tetrazolium staining and normalized for area-at-risk (IA/AAR). Ischemic preconditioning (5 min global ischemia and 10 min reperfusion) or adenosine (20 micro M, 5 min) perfusion reduced infarct size (IA/AAR) to 17+/-3 and 14+/-2%, respectively (controls: 59+/-2%). Ischemic preconditioning and adenosine-mediated cardioprotection were completely blocked (57+/-2 and 61+/-4% IA/AAR, respectively) in the presence of a rabbit A1-selective concentration (50 nm) of the antagonist BWA1433 (rabbit A1 Ki: 3 nm; A3 Ki; 746 n m). Thus, whereas recent studies have demonstrated that selective A1 or A3 receptor agonists can both pharmacologically mimic IP, the results of the present study suggest that the adenosine-mediated component of IP in the isolated rabbit heart is preferentially mediated by adenosine A1 receptors, potentially due to adenosine's selectivity for this receptor subtype.

Maximizing plasmid stability and production of released proteins in Yersinia enterocolitica.

Virulent serotypes of Yersinia enterocolitica carry a plasmid (pYV) encoding a family of proteins that are released into the medium and whose expression is temperature and calcium regulated. The plasmid is easily lost from cells during their growth in the laboratory. We have used sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting with a monoclonal antibody (3.2C) that is specific for a 25-kDa released protein to show that 32 degrees C is the lowest temperature at which plasmid-encoded proteins are expressed in quantity. The highest calcium concentration allowing full expression of these proteins was 445 to 545 microM at 32 degrees C. Calcium concentrations of 745 microM and above at 37 degrees C completely prevented the loss of pYV during multiple subcultures, while at 32 degrees C, calcium concentrations of 245 microM and greater were sufficient to stabilize the plasmid. Growth of Y. enterocolitica at pH 5.5 was slower than at neutral pH values, but it also resulted in greatly increased stability of pYV. These studies showed that bacterial growth, retention of pYV, and expression of plasmid-encoded proteins may be maximized at 32 degrees C with 445 microM calcium and that pYV stability is enhanced by growth at low pH. These observations suggest new approaches for isolation of plasmid-bearing virulent strains of Y. enterocolitica from samples contaminated with this organism and also may improve our understanding of pYV retention in vivo.

Specific fears and phobias. Epidemiology and classification.

BACKGROUND: Data on eight specific fears representing DSM-III-R simple phobia were analysed to evaluate: (a) their prevalence and (b) the validity of subtypes of specific phobia defined by DSM-IV. METHOD: A modified version of the Composite International Diagnostic Interview was administered to a probability sample of 8098 community respondents. Correlates of responses to questions concerning these fears were analysed. RESULTS: The most prevalent specific fears were of animals among women, and of heights among men. Slight evidence was found for specific phobia subtypes. Number of fears, independent of type, powerfully predicted impairment, comorbidity, illness course, demographic features, and family psychopathology. CONCLUSION: Number of specific fears may mark a general predisposition to psychopathology. More detailed information is needed to resolve the question of specific phobia subtypes.

Selective activation of adenosine A3 receptors with N6-(3-chlorobenzyl)-5'-N-methylcarboxamidoadenosine (CB-MECA) provides cardioprotection via KATP channel activation.

OBJECTIVE: The aim of this study was to characterize the adenosine A3 receptor agonist, N6-(3-chlorobenzyl)-5'-N-methylcarboxamidoadenosine (CB-MECA), evaluate its ability to reduce myocardial ischemia/reperfusion injury and determine the role of KATP-channel activation in A3 receptor-mediated cardioprotection. METHODS: Binding affinities and adenylate cyclase inhibition were examined in CHO cells expressing rabbit recombinant adenosine A1 or A3 receptors. Infarct size (normalized for area-at-risk; % IA/AAR) was measured in buffer-perfused rabbit hearts exposed to 30-min regional ischemia and 120 min of reperfusion. RESULTS: CB-MECA was 100-fold selective for A3 vs. A1 receptors (A3 Ki: 1 nM; A1 Ki: 105 nM). Five-min perfusion with CB-MECA before ischemia/reperfusion elicited a concentration-dependent reduction in infarct size (EC50: 0.3 nM). The CB-MECA-dependent cardioprotection (control: 58 +/- 2; CB-MECA: 21 +/- 3% IA/AAR) was unchanged by an A1-selective concentration of the antagonist, BWA1433, but was completely prevented (P < 0.05) by a nonselective (A1/A3) concentration (55 +/- 6% IA/AAR). The KATP channel inhibitors, glibenclamide and 5-HD, had no effect on control infarct size, yet significantly (P < 0.05) blunted the CB-MECA-dependent cardioprotection (glibenclamide: 49 +/- 6; 5-HD: 58 +/- 4% IA/AAR). CONCLUSIONS: CB-MECA is a novel 100-fold A3 receptor-selective agonist which should prove useful for elucidating A3-dependent mechanisms in the rabbit heart. Selective stimulation of adenosine A3 receptors with CB-MECA reduces myocardial ischemia/reperfusion injury via a mechanism which involves activation of KATP channels.

Selective adenosine A3 receptor stimulation reduces ischemic myocardial injury in the rabbit heart.

OBJECTIVE: The aim of this study was to determine whether selective activation of the adenosine A3 receptor reduces infarct size in a Langendorff model of myocardial ischemia-reperfusion injury. METHODS: Buffer-perfused rabbit hearts were exposed to 30 min regional ischemia and 120 min of reperfusion. Infarct size was measured by tetrazolium staining and normalized for area-at-risk (IA/AAR). RESULTS: Preconditioning by 5 min global ischemia and 10 min reperfusion reduced infarct size (IA/AAR) to 19 +/- 4% (controls: 67 +/- 5%). Replacing global ischemia with 5 min perfusion of the rabbit A3-selective agonist, IB-MECA (A3 Ki: 2 nM; A1 Ki: 30 nM) elicited a concentration-dependent reduction in infarct size; 50 nM IB-MECA reduced IA/AAR to 24 +/- 4%. The A1-selective agonist, R-PIA (25 nM) reduced IA/AAR to a similar extent (21 +/- 6%). However, while the cardioprotective effect of R-PIA was significantly inhibited (54 +/- 7% IA/AAR) by the rabbit A1-selective antagonist, BWA1433 (50 nM), the IB-MECA-dependent cardioprotection was unaffected (28 +/- 6% IA/AAR). A non-selective (A1 vs. A3) concentration of BWA1433 (5 microM) significantly attenuated the IB-MECA-dependent cardioprotection (61 +/- 7% IA/AAR). CONCLUSIONS: These data clearly demonstrate that selective A3 receptor activation provides cardioprotection from ischemia-reperfusion injury in the rabbit heart. Furthermore, the degree of A3-dependent cardioprotection is similar to that provided by A1 receptor stimulation or ischemic preconditioning.

One-stage reconstruction for defects caused by cancrum oris (noma).

Cancrum oris is a disease process that has been described for centuries, but now presents primarily in developing countries. The disease in known to occur in association with poor nutrition and exanthematous infections. The acute disease occurs usually in young children, and the infectious process causes destruction of the involved orofacial tissues with variable degrees of tissue loss and scar reaction in those who are affected and survive. The chronic sequelae of the acute disease process often require reconstructive surgery. We present the natural history of the disease process and its causes, and demonstrate the wide spectrum of resulting defects that challenge the reconstructive surgeon. Because of the socioeconomic situation inherent with these patients and the volume of patients in need of treatment with this disease, innovative and efficient treatment is required. We have demonstrated methods of reconstructive surgery that differ from the multiple staged procedures described in previous studies by allowing for one-stage surgical reconstruction of even the most complex cases. This allows for treatment of the majority of patients in their native countries in a cost-effective and safe manner, and treatment of more severely afflicted individuals in modern medical centers without their having to spend a long time period away from their homes.

Studies of the candidate genes TGFB2, MSX1, TGFA, and TGFB3 in the etiology of cleft lip and palate in the Philippines.

Population-based candidate-gene studies can be an effective strategy for identifying genes involved in the etiology of disorders where family-based linkage studies are compromised by lack of access to affected members, low penetrance, and/or genetic heterogeneity. We evaluated association data for four candidate genes using a population from the Philippines that is genetically separate from previously studied Caucasian populations. Case ascertainment was made possible by collaboration with Operation Smile, a volunteer medical organization, which facilitated identification of a large number of cases for study. A new allelic variant of transforming growth factor-beta 3 was identified to use in these studies. After exclusion of syndromic cases of cleft lip and palate, no evidence for association with previously reported allelic variants of transforming growth factor-beta 2 (TGFB2), homeobox 7 (MSX1), or transforming growth factor-alpha (TGFA), or with the new TGFB3 variant was detected. Previous association studies using Caucasian populations of nonsyndromic cleft lip and/or palate (CL/P) and cleft palate only (CPO) have strongly suggested a role for TGFA in the susceptibility of clefting in humans. Exclusion of significant association in a non-Caucasian population for TGFA suggests that TGFA plays less of a role than it does in Caucasians. This may be due to multiple or different genetic and/or environmental factors contributing to the etiology of this most common cranio-facial anomaly in the Philippine population.

Clinical and epidemiologic studies of cleft lip and palate in the Philippines.

Clinical and epidemiologic studies of defined geographic populations can serve as a means of establishing data important for genetic counseling and as a first step in identifying strategies best suited for identification of causes. Under the sponsorship of Operation Smile International, clinical, genetic, and epidemiologic studies were carried out at six sites within the Philippines between 1989 and 1996. Patients who were being evaluated for surgical repair of craniofacial anomalies (primarily clefts of the lip and palate) were briefly examined for the presence of associated anomalies, and a family history was obtained to look for the frequency of cleft lip and palate in siblings. Birth records of 47,969 newborns over an 8-year period at one hospital in Bacolod City in the province of Negros Occidental were reviewed. Medical records of infants born with clefts of the lip and/or palate and other major anomalies were reviewed and birth prevalence rates calculated. Findings include a birth prevalence of 1.94 per 1000 live births for cleft lip with/without palate in the Philippines. Recurrence rates in siblings for nonsyndromic clefts of the lip and palate were 23 per 1000 for cleft lip with or without cleft palate, and 14 per 1000 for cleft palate only. The percentage of clefts associated with multiple anomalies was 21% at birth and 6% for individuals examined during the screening process, providing evidence for a high postnatal death rate. These data provide groundwork for additional etiologic studies including segregation analysis and molecular genetic studies involving linkage or association, as well as for studies of environmental contributions to clefting such as vitamin deficiencies. Preliminary molecular analysis using an association approach is reported in a companion paper. The findings suggest a high incidence of cleft lip and palate in native-born Filipinos.

Agoraphobia, simple phobia, and social phobia in the National Comorbidity Survey.

BACKGROUND: Data are presented on the general population prevalences, correlates, comorbidities, and impairments associated with DSM-III-R phobias. METHODS: Analysis is based on the National Comorbidity Survey. Phobias were assessed with a revised version of the Composite International Diagnostic Interview. RESULTS: Lifetime (and 30-day) prevalence estimates are 6.7% (and 2.3%) for agoraphobia, 11.3% (and 5.5%) for simple phobia, and 13.3% (and 4.5%) for social phobia. Increasing lifetime prevalences are found in recent cohorts. Earlier median ages at illness onset are found for simple (15 years of age) and social (16 years of age) phobias than for agoraphobia (29 years of age). Phobias are highly comorbid. Most comorbid simple and social phobias are temporally primary, while most comorbid agoraphobia is temporally secondary. Comorbid phobias are generally more severe than pure phobias. Despite evidence of role impairment in phobia, only a minority of individuals with phobia ever seek professional treatment. CONCLUSIONS: Phobias are common, increasingly prevalent, often associated with serious role impairment, and usually go untreated. Focused research is needed to investigate barriers to help seeking.

Cleft palate closure in the neonate: preliminary report.

Our recent experience with cleft palate closure in the neonatal period (within 28 days of birth) is reviewed in this study. The research involved a series of 21 neonates who presented with untreated cleft palates and underwent a modified Veau-Wardill-Kilner palate closure by a single surgeon between 1991 and 1994. The postoperative clinical follow-up ranged from 8 to 37 months (mean 18 months). All complications discussed do not seem to occur more frequently when surgery is done at this age than at an older age. Our findings demonstrate that cleft palate closure can be safely performed in the neonatal period; we do not, however, recommend that the standard approach should be changed based on this preliminary report.

The effect of very early cleft palate closure on the need for ventilation tubes in the first years of life.

The otologic consequences associated with cleft palates are well known. Closure of palatal clefts within the first weeks of life has many potential benefits, including improved feeding and cosmesis. The potential otologic benefits of very early closure are not known. Eighteen newborns have undergone closure of their palatal clefts within the first month of life with subsequent otolaryngology follow-up through our craniofacial center. Thirteen (72%) of the 18 still required placement of ventilation tubes during their first 3 years of life because of persistent effusion (for more than 120 days) or recurrent infection (more than four episodes in 6 months or more than six episodes in 12 months). Very early cleft palate closure may not significantly alter the need for ventilation tubes in children with palatal clefts.

Monoclonal antibody to a major outer membrane protein of feline Chlamydia psittaci: antibody specificity and anti-idiotype antibody production.

A murine monoclonal antibody, F1-8, was developed against the purified major outer membrane protein (MOMP) of Chlamydia psittaci feline pneumonitis (FPn). F1-8 showed a serotype-specific activity against intact Fpn elementary bodies in a micro-immunofluorescence assay. In immunoblot, F1-8 reacted only with the Fpn MOMP but did not react with the MOMPs from other strains of C. psittaci and C. trachomatis. F1-8 neutralized Fpn infectivity in L929 cell culture in a dose-dependent and complement independent fashion. These results suggested that the monoclonal antibody (mAb) binds with an epitope on the MOMP region that is exposed at the cell surface and plays an important role in FPn infection. Polyclonal anti-idiotype (anti-Id) antibodies to mAb F1-8 were elicited by F1-8 coupled to keyhole limpet hemocyanin. These anti-Id antibodies inhibited F1-8 binding to FPn MOMP.

Vasoconstrictor action of angiotensin I-convertase and the synthetic substrate (Pro11,D-Ala12)-angiotensin I.

A chymase (also referred to as angiotensin I-convertase) specific for the conversion of angiotensin (Ang) I to Ang II has been identified in human heart. This serine protease is also present in dog and marmoset vasculature. We examined the vasoconstrictor effects of Ang II putatively generated from an angiotensin-converting enzyme (ACE)-resistant convertase synthetic substrate (SUB) in vivo and in vitro. In marmosets, SUB (7 to 700 micrograms/kg i.v.) or Ang I (0.1 to 30 micrograms/kg) caused similar dose-dependent increases in mean arterial pressure (10 to 100 mm Hg) and decreases in heart rate. Pressor effects of SUB were slightly attenuated at low (but not high) doses by captopril (CAP, 1 mg/kg i.v.) and blocked by losartan (5 mg/kg i.v.); in contrast Ang I pressor effects were substantially blocked by both. In isolated canine superior mesenteric artery, Ang I-induced contraction was eliminated by losartan and reduced but not eliminated by 10 mumol/L CAP. When combined with the serine protease inhibitor chymostatin, CAP eliminated Ang I-induced contraction, but chymostatin alone had no effect. SUB-induced contraction was not blocked by CAP but was equally blocked by chymostatin (25 mumol/L) alone or by the combination of CAP (10 mumol/L) and chymostatin (25 mumol/L); losartan (10 mumol/L) eliminated SUB-induced responses. Previous studies have suggested that Ang I-convertase is important for production of Ang II in the heart. Our results are consistent with a potential role for Ang I-convertase in the production of Ang II in the vasculature, resulting in Ang II-mediated vasoconstriction.