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Biomedical subjects

C Kim

Publications and source records attributed to C Kim.

At least 19 recordsLinked to original sources
PubMed1996

Kinetic analysis of the interaction of cidofovir diphosphate with human cytomegalovirus DNA polymerase.

Cidofovir [CDV,(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, HPMPC] is an acyclic cytosine nucleoside phosphonate analog with potent in vitro and in vivo activity against a broad spectrum of herpesviruses. CDV diphosphate (CDVpp), the putative antiviral metabolite of CDV, is a competitive inhibitor of dCTP and an alternate substrate for human cytomegalovirus (HCMV) DNA polymerase. HCMV DNA polymerase used a synthetic DNA primer-template with a Km value of 90 +/- 8 nM and incorporated dCTP approximately 42 times more efficiently than CDVpp. HCMV DNA polymerase also utilized a synthetic DNA primer containing a single molecule of CDV at the 3'-terminus. The Km value for this DNA primer-template was 165 +/- 42 nM and incorporation of dCTP was approximately 17 times more efficient than that of CDVpp. The slower rate of incorporation of CDVpp was due mostly to the higher Km value of CDVpp toward the enzyme-primer-template complexes. These data demonstrate that incorporation of a single CDV into DNA by HCMV DNA polymerase does not lead to chain termination.

Animals↗
PubMed1996

Antitumor sulfonylurea-inhibited NADH oxidase of cultured HeLa cells shed into media.

Conditioned culture media of HeLa S cells contain a soluble NADH oxidase activity inhibited by the antitumor sulfonylurea, N-(4-methylphenylsulfonyl)-N' -(4-chlorophenyl)urea (LY181984) similar to that associated with the outer surface of the plasma membrane. This activity was absent from media in which cells had not been grown and was present in conditioned culture media from which cells had been removed by centrifugation both for serum-containing and serum-free media. The Km with respect to NADH and response to thiol reagents were similar to those of the corresponding activity of the plasma membrane of HeLa cells. The conditioned HeLa culture media bound [3H]LY181984 with high affinity. Both antitumor sulfonylurea-inhibited and -resistant forms of the NADH oxidase were isolated by free-flow electrophoresis. The antitumor sulfonylurea-inhibited activity was purified to apparent homogeneity and was identified with a 33.5 kDa protein with an isoelectric point of about pH 4.5. The 33.5 kDa protein from conditioned HeLa culture medium both bound [3H]LY181984 and retained an LY181984-inhibited NADH oxidase activity. A polyclonal antisera was raised in rabbits to the purified 33.5 kDa constituent from conditioned HeLa culture medium. The antisera blocked the activity of the LY181984-inhibited NADH oxidase activity, immunoprecipitated the activity and reacted with a 33.5 kDa protein on Western blots while preimmune sera did not. Also inhibited and immunoprecipitated was NADH oxidase activity from HeLa plasma membranes. The findings are consistent with the 33.5 kDa drug-inhibited NADH oxidase activity of the culture media being a shed form of the corresponding native 34 kDa antitumor sulfonylurea-inhibited NADH oxidase activity of the HeLa cell plasma membrane.

Antineoplastic Agents↗
PubMed1996

A pathologic study of Hodgkin's disease in Korea and its association with Epstein-Barr virus infection.

BACKGROUND: The incidence of Hodgkin's disease (HD) in Korea and other Asian countries is much lower than in western countries and its association with the Epstein-Barr virus has not been well characterized. METHODS: We evaluated the clinical, morphologic, and immunohistochemical features of 87 patients with Hodgkin's disease and also analyzed patients for Epstein-Barr virus (EBV) using in situ hybridization for EBV DNA, RNA, and latent membrane protein (LMP1). RESULTS: There were 68 males and 19 females, with a mean age of 38 years. Mixed cellularity was the most prevalent subtype. Expression of EBV RNA (EBER:EBV-encoded RNA) was detected in 60 of 87 cases (69%): 1 of 1 (100%) with lymphocyte predominance, nodular; 4 of 7 (57%) with lymphocyte predominance, diffuse; 10 of 17 (59%) with nodular sclerosis; 38 of 51 (75%) with mixed cellularity; and 7 of 11 (64%) with lymphocyte depletion. Positivity was higher in advanced clinical stages; 4 of 7 patients (57%) with Stage I; 6 of 12 patients (50%) with Stage II: 7 of 9 patients (75%) with Stage III; and 5 of 5 patients (100%) with Stage IV HD EBV DNA was detected in 9 of 25 cases tested (36%). LMP1 was seen in 39 of 87 cases (45%). EBER and LMP1 positivity were higher in children and older adults than in adults aged between 15-50 years. Immediate early mRNAs (BHLF:Bam H-fragment, lower strand frame) was seen in a single patient. CONCLUSIONS: HD in Korea showed a high incidence of mixed cellularity subtype and a high prevalence of EBV. EBV was detected in all subtypes, including a case of nodular lymphocytic predominance, and in all age groups, and showed correlation with mixed cellularity subtype and higher clinical stage. The expression of EBER and LMP were more frequently seen in children and older adults, suggesting a lowered immune surveillance in those age groups or a different pathophysiology of HD among different age groups.

Adolescent↗
PubMed1996

Role of interleukin 6 in epithelial hyperproliferation and bone resorption in middle ear cholesteatomas.

Locally produced pro-inflammatory cytokines are considered to play an important role in the initiation and/or maintenance of inflammatory diseases. In cholesteatomatous lesions there are increased levels of some cytokines and inflammatory mediators like interleukin 1, tumor necrosis factor and colony-stimulating factor, etc. Interleukin 6 (IL-6) can be produced by different cells present in cholesteatoma (e.g. keratinocytes, lymphocytes, fibroblasts and macrophages). Until now, no data have been available on the role of IL-6 in cholesteatoma. In this study we used immunohistochemistry to investigate the presence and distribution of IL-6 in tissue samples from cholesteatoma patients. Levels of the cytokine were quantified in tissue extracts using an enzyme-linked immunosorbent assay. Finally, the presence of biologically active IL-6 was analyzed in the murine cell line 7TD1. Human skin samples obtained from the external ear canal were used as controls. Using the anti-IL-6 antibody in an alkaline phosphatase anti alkaline phosphatase technique, a moderate diffuse staining of the whole epidermis was observed in sections of normal skin. In cryostat sections of cholesteatoma samples, a stronger staining of the whole epithelium was observed. Many of the cells infiltrating the cholesteatoma stroma also showed positive immunostainings. The concentration of IL-6 in relation to the total protein concentration in cholesteatoma (119.33 +/- 30) were higher than in human skin (9.16 +/- 13). While IL-6 activity was not detected in skin samples, two of the ten cholesteatoma samples studied showed a stimulatory effect when incubated with the cell line 7TD1. The overexpression of IL-6 in middle ear cholesteatoma suggests a participation of this cytokine in some of the clinical features seen: epithelial hyperproliferation and bone resorption. The absence of biological activity in the majority of the cholesteatoma samples points to the presence of natural inhibitors for IL-6.

Bone Resorption↗
PubMed1996

Quantitative analysis of interleukin-1-alpha gene expression in middle ear cholesteatoma.

Regardless of its origin, cholesteatoma is characterized by the presence of a keratinizing epithelium with an hyperproliferative behavior leading to a very important bone resorption. Previous studies have demonstrated overexpression of interleukin-1 (IL-1 protein in middle ear cholesteatoma by immunohistochemistry and enzyme-linked immunosorbent assay, suggesting a significant role for IL-1-alpha. In this study, the presence of IL-1-alpha messenger ribonucleic acid (mRNA) was quantified by in situ hybridization on frozen sections (n = 10) and by computer-assisted image analysis. Human skin obtained from the external ear canal (n = 10) was used as the control. A higher percentage of cells hybridized for the antisense probes IL-1-alpha mRNA was found in cholesteatoma epithelium. Furthermore, keratinocytes of the suprabasal cell layers were also found to contain specific hybridizations. Some cells in cholesteatoma stroma also contained IL-1-alpha mRNA transcripts. The results of this study confirm the central role of IL-1-alpha in the epithelium hyperproliferation and bone resorption observed in middle ear cholesteatoma.

Cholesteatoma, Middle Ear↗
PubMed1996

Variability of fine particle deposition in healthy adults: effect of age and gender.

Recent epidemiologic studies suggest increased mortality among the elderly in association with particulate air pollution. We investigated the variability in fractional deposition (DF) of inhaled particles (2 microns mass median aerodynamic diameter [MMAD]) in 62 subjects with normal lung function, aged 18 to 80 yr. Each subject inhaled 2-microns monodisperse carnauba wax particles while following a breathing pattern previously determined by respiratory inductance plethysmography in that subject (i.e., particles inhaled) was determined by laser aerosol photometry and pneumotachometry at the mouth. DF (mean DF = 0.29 +/- 0.06 (ages 18 to 40 yr), 0.29 +/- 0.07 (ages 41 to 60 yr), and 0.26 +/- 0.06 (age over 60 yr) was independent of age. There was a tendency toward greater DF in female than in male subjects; DF = 0.30 +/- 0.07 (females) and 0.27 +/- 0.06 (males) (p = 0.06); however, because the males had 45% higher minute ventilations than the females, the deposition rate (Drate), or particles depositing per unit of time, was 30% greater in males than in females (p = 0.004). Multiple regression analysis showed that among all subjects, the variability in DF was best predicted by variability in the breathing period (T) associated with the pattern used to breathe the particles, and by the subject's specific airway resistance (sRAW). These results may prove useful in determining age- and gender-relative risks that may be associated with the inhalation of pollutant particles in ambient air.

Adolescent↗
PubMed1996

Progesterone together with estradiol promotes luteinizing hormone beta-subunit mRNA stability in rat pituitary cells cultured in vitro.

The present study examined the role of ovarian steroids, estradiol and/or progesterone in the regulation of luteinizing hormone beta-subunit (LH-beta) mRNA levels and LH release in the rat anterior pituitary cells cultured in vitro. When estradiol (10 nmol/l) and/or progesterone (100 nmol/l) were added to the cultures, neither estradiol or progesterone nor both together altered the basal LH-beta mRNA levels or LH release. Continuous exposure to gonadotropin-releasing hormone (GnRH, 0.2 nmol/l) for 24 h markedly induced LH-beta mRNA accumulation, and in this experimental condition, progesterone alone and progesterone + estradiol further augmented GnRH-induced LH-beta mRNA levels and LH release. Then we explored further the possibility that ovarian steroids are involved in modulating LH-beta mRNA stability in cultured rat pituitary cells where transcription was inhibited by actinomycin D. Anterior pituitary cells were preincubated with GnRH (0.2 nmol/l) for 16 h and, after removing GnRH from culture medium, the cells were incubated further in the presence of actinomycin D (5 mumol/l) for 24 h. The LH-beta mRNA levels gradually declined to about 30% of the control values (zero time point after GnRH removal) in a time-dependent manner. During this period, either progesterone alone or progesterone + estradiol clearly blocked the degradation of LH-beta mRNA species. These results indicate that ovarian steroids promote LH-beta mRNA stability, thereby contributing to the maintenance of GnRH-stimulated LH-beta mRNA levels.

Animals↗
PubMed1995

Recombinant human replication protein A binds to polynucleotides with low cooperativity.

Replication protein A (RPA) is a multisubunit single-stranded DNA-binding protein that is involved in multiple aspects of cellular DNA metabolism. We have determined quantitative estimates of the binding parameters of human replication protein A (hRPA) from equilibrium binding isotherms. The intrinsic binding constant (K) and cooperativity parameter (omega) were determined from analysis of changes in the intrinsic fluorescence of hRPA that occurred upon binding single-stranded DNA homopolynucleotides. The cooperativity of hRPA binding to both poly(dT) and poly(dA) was found to be low (omega = 10-20) at all NaCl concentrations examined (0.3-2 M). In contrast, the apparent binding affinity (K omega) of RPA decreased significantly with increasing salt concentration, such that log [NaCl]/log K omega was -2.8 for poly(dT) and -4.8 for poly(dA). We conclude that the salt dependent decrease in binding affinity resulted from changes in the intrinsic binding constant (K). These data suggest that the interaction of hRPA with single-stranded DNA involves significant electrostatic interactions, similar to other single-stranded DNA-binding proteins. The apparent binding affinity (K omega) of RPA was higher for poly(dT) than for poly(dA); extrapolation of our data indicated that the apparent binding affinity at 0.2 M NaCl was 1.6 x 10(10) M-1 for poly(dT) and 1.1 x 10(9) M-1 for poly(dA).

DNA, Single-Stranded↗
PubMed1995

Interleukin-13 effectively down-regulates the monocyte inflammatory potential during traumatic stress.

OBJECTIVES: To determine the potential of interleukin-13 (IL-13) to modify in vitro lipopolysaccharide-induced monocyte-macrophage (MO) activity in human cells from individuals who had sustained either major mechanical or burn injury and to investigate whether the effect of IL-13 is different on MOs that have been preactivated under traumatic stress than on monocytic cells from healthy volunteers. DESIGN: Peripheral MOs from 20 controls and 16 patients after major burn or mechanical trauma were separated on days 1, 3, 5, and 7 after injury and incubated with lipopolysaccharide (1 microgram/mL) in the presence or absence of IL-13 (10 ng/mL) for 4 hours and for 20 hours. Thereafter, the following measures were determined from the culture supernatants: neopterin, nitric oxide, tumor necrosis factor alpha, IL-1 beta, IL-6, and IL-8. RESULTS: Ex vivo lipopolysaccharide-activated MOs, compared with control cells, displayed considerably enhanced inflammatory activity during the immediate posttraumatic course, with a substantial and consistent elevation of levels of tumor necrosis factor alpha and IL-6. The addition of human recombinant IL-13 to the MO cultures resulted in an effective down-regulation of the synthesis of tumor necrosis factor alpha, IL-1 beta, and IL-6 as well as IL-8, showing an average reduction of mediator production to two thirds of the value found in corresponding sole lipopolysaccharide-stimulated cultures. The impact of human recombinant IL-13 on control MOs was almost identical for IL-6 and IL-1 beta, slightly lower for IL-8, and nonexistent for tumor necrosis factor alpha. CONCLUSION: From this study and preexisting findings, we conclude that, based on its biologic properties, IL-13 should be tested as a biologic response modifier for acute states of trauma-induced host defense deficiency.

Adult↗
PubMed1995

Evaluation of a fluorescence feedback system for guidance of laser angioplasty.

BACKGROUND AND OBJECTIVE: Laser-induced fluorescence spectroscopy (LIFS) may be capable of guiding laser angioplasty by discriminating normal and atherosclerotic artery and by determining catheter-tissue environment. Previous optical multichannel analyzer based LIFS systems have been expensive and cumbersome. To simplify LIFS, a system based on photomultiplier tubes was developed and evaluated. STUDY DESIGN/MATERIALS AND METHODS: Tissue fluorescence was induced by a helium cadmium laser (wavelength = 325 nm, power = 0.2-0.5 mW), collected by clinical multifiber laser angioplasty catheters and directed through one of two filters (10 nm bandpass, 380 nm or 440 nm peak transmission) to a photomultiplier tube. An LIFS ratio was defined as the relative intensity at 380:440 nm after calibration with an elastin fluorescence spectrum; 157 coronary artery cadaveric specimens were evaluated spectroscopically and histologically. To evaluate the utility of LIFS to optimize catheter position by determining catheter-tissue contact, by determining saline dilution of blood, and by orienting eccentric multifiber catheters a new variable, the total fluorescence intensity (TFI) was defined as the sum of arterial fluorescence intensities at 380 nm and 440 nm. TFI was recorded in vitro through multifiber catheters from 20 arterial specimens in vitro in blood and evaluated as a function of the catheter-to-tissue distance (d) over a range from 0 to 400 mu. RESULTS: Defining normal specimens as those with an intimal thickness < or = 200 mu, and atherosclerotic as those with an intimal thickness > 200 mu, 47/50 (94%) normal and 85/107 (79%) atherosclerotic specimens were correctly classified using a threshold LIFS ratio of 2.0. Mean (+/- SE) normal ratio was 1.76 +/- 0.02 and mean atherosclerotic ratio was 2.78 +/- 0.08 (P < or = 0.01). The classification accuracy of atherosclerotic specimens increased with intimal thickness so that 95% of atherosclerotic specimens (69/73) with intimal thickness > or = 400 mu were correctly classified. TFI was capable of determining catheter-tissue contact as maximal TFI was recorded with the catheter in contact with the tissue (d = 0 mu) and decreased markedly with distance (to 52 +/- 6% at d = 100 mu, 19 +/- 4% at d = 200 mu, and 3 +/- 1% at d = 300 mu). TFI was recorded from ten arterial specimens in blood/saline mixtures ranging in hematocrit from 0% (saline) to 50% (whole blood). TFI was capable of detecting saline hemodilution of blood as TFI decreased markedly at higher hematocrits such that TFI could only by recorded at hematocrits < 10% for catheter-to-tissue distances > or = 300 mu. TFI was recorded through ecentric multifiber catheters from 25 arterial specimens and eval-uated as a function of the degree of catheter-tissue overlap. TFI was capable of detecting maximal catheter-tissue overlap as TFI correlated linearly with the area (A) of overlap (TFI = 1.12 A + .07, r = 0.92). CONCLUSIONS: By discriminating atherosclerotic from normal tissue and by confirming catheter-tissue contact and saline hemodilution, fluorescence feedback should minimize irradiation of normal tissue and/or blood and enhance the safety and efficacy of laser angioplasty.

Angioplasty, Laser↗
PubMed1995

Anaesthetic induction in a child with end-stage cardiomyopathy.

The purpose of this clinical report is to discuss the anaesthetic management of a patient with end-stage cardiomyopathy. An eight-year-old boy sustained electro-mechanical dissociation following a "standard anaesthetic induction" but was subsequently successfully anaesthetized using a combination of etomidate, midazolam, lidocaine, vecuronium and glycopyrrolate. Anaesthetic techniques and their relationship to the specific category of cardiomyopathy (dilated, hypertrophic or restrictive) are discussed. The potential detrimental effects of anaesthetic sympatholysis, myocardial depression and negative chronotropy on cardiac output are explained.

Anesthesia, Intravenous↗
PubMed1995

IV compared with brachial plexus infusion of butorphanol for postoperative analgesia.

In a randomized, double-blind, controlled study, we have compared two groups of patients receiving either continuous systemic i.v. or continuous brachial plexus infusion of butorphanol for analgesia after operations on the upper extremities. Twenty-two patients undergoing elective upper extremity surgery were allocated randomly to one of two groups to receive either butorphanol i.v. and saline injected into the brachial plexus sheath (i.v. group) or butorphanol injected into the brachial plexus sheath and saline i.v. (brachial plexus group). After surgery on the upper extremity under continuous axillary brachial plexus block, each patient received a continuous infusion of butorphanol either i.v. or into the brachial plexus sheath at a dose of 83.3 micrograms h-1. Concurrently, a saline infusion was given via the alternate route. Patients rated their pain on a 10-cm visual analogue scale (VAS). VAS scores in the two groups did not differ up to 6 h and 24 h after operation. From 9 h until 24 h after operation, pain scores were significantly higher in the i.v. group than in the brachial plexus group. The VAS score 9 h after operation was 3.3 (SD 2.7) in the i.v. group and 0.6 (0.9) in the brachial plexus group (P < 0.01); 12 h after operation 2.7 (1.8) in the i.v. group and 0.6 (0.9) in the brachial plexus group (P < 0.01); 18 h after operation 1.7 (1.0) in the i.v. group and 0.7 (1.0) in the brachial plexus group (P < 0.05); and 24 h after operation 3.2 (2.4) in the i.v. group and 0.7 (1.2) in the brachial plexus group (P < 0.01). We conclude that continuous injection of butorphanol into the brachial plexus sheath provided superior analgesia compared with continuous i.v. injection.

Adolescent↗
PubMed1995

Comparison of continuous brachial plexus infusion of butorphanol, mepivacaine and mepivacaine-butorphanol mixtures for postoperative analgesia.

We have reported recently that continuous administration of butorphanol into the brachial plexus sheath provided analgesia of a quality superior to that of continuous i.v. administration. In the present study, we have compared postoperative pain relief produced by continuous infusion of one of three types of solution into the axillary sheath: opioid alone, local anaesthetic alone or a mixture of local anaesthetic and opioid. In patients undergoing upper extremity surgery with continuous axillary brachial plexus block, we injected one of the three solutions into the axillary neurovascular sheath: butorphanol 2 mg (group B), 0.5% mepivacaine alone (group M) and 0.5% mepivacaine-butorphanol (group MB); the volume of each solution was 50 ml, administered at a rate of 50 ml per 24 h. At 3 h after operation, visual analogue scale (VAS) scores were significantly higher in group M than in group MB (P < 0.01), and higher in group B than in group MB (P < 0.05).

Adolescent↗
PubMed1995

d-Tubocurarine accentuates the burn-induced upregulation of nicotinic acetylcholine receptors at the muscle membrane.

BACKGROUND: Increases in acetylcholine receptors (AChRs) at the muscle membrane, induced by burn injury, have been associated with a hyperkalemic response to succinylcholine and resistance to d-tubocurarine-like drugs. Muscle relaxants often are administered to burn-injured patients in the intensive care unit to facilitate mechanical ventilation. This study in rats tested whether continuous administration of d-tubocurarine in subparalytic doses exaggerates the upregulation of AChRs induced by burn trauma. Subparalytic doses were used to avoid the confounding effects of immobilization. METHODS: Three days after an approximate 50% body surface area burn or sham injury, the animals received an infusion of 3.03 +/- 0.05 micrograms/h of d-tubocurarine or equal volume of saline directly to the left gastrocnemius muscle via catheter connected to a subcutaneously implanted osmotic pump. After 7 days of d-tubocurarine or saline infusion, the AChRs were quantitated using 125I-alpha-bungarotoxin. The AChRs on the d-tubocurarine or saline-infused left gastrocnemius were compared to the contralateral gastrocnemius in the same group. The right or left gastrocnemius AChRs were compared to the ipsilateral muscles between groups. These intra- and intergroup comparisons allowed the delineation of the effects of catheter irritation, burns, or d-tubocurarine on AChRs. RESULTS: Daily examination of the withdrawal response to toe-pinch revealed no evidence of paralysis. Weight loss in the burn-injury animals receiving d-tubocurarine or saline was similar, confirming that the infusion of d-tubocurarine did not impair the mobility of the animals to move and feed. The plasma d-tubocurarine concentration after 7 days of infusion was 26.0 +/- 12 ng/ml (mean +/- SE). Regardless of burn or sham injury or of d-tubocurarine or saline infusion, the concentration of AChRs on the left was consistently greater than in the contralateral right gastrocnemius muscles within the same group, indicating that manipulation of the area alone can result in upregulation of AChRs. The AChRs in the right gastrocnemius of burn-injured animals were greater than those in the same muscle of sham-injured animals, regardless of saline (7.24 +/- 0.9 vs. 5.7 +/- 0.5 fmoles/mg protein, P = 0.06) or d-tubocurarine (7.3 +/- 0.4 vs. 5.7 +/- 0.5, P < 0.05) infusion to the burn-injury groups. AChRs in the left gastrocnemius of burn-injury animals receiving d-tubocurarine were significantly greater than those in burn- or sham-injury animals receiving saline (13.9 +/- 1.1 vs. 9.8 +/- 1.2 and 7.1 +/- 0.5 fmoles/mg protein, respectively, P < 0.05). CONCLUSIONS: Burn-induced upregulation of AChRs is accentuated by infusion of subparalytic doses of d-tubocurarine. Concomitant administration of d-tubocurarine to burn-injured patients may result in further exaggeration of the aberrant responses to neuromuscular relaxants.

Animals↗
PubMed1995

Map dynamic ranges versus duration of hearing loss in cochlear implantees.

In order to assess the relationship of factors such as age, cause of deafness, use of hearing aids, duration of hearing loss, and age at onset of hearing loss, with the size of map dynamic ranges (DRs), 34 postlingually and 8 prelingually deaf users of the Nucleus cochlear implant system were analyzed according to the sizes of map DRs. Lack of auditory stimulation for a longer period than 10 years might be one of the most important factors associated with a reduced map DR. Use of hearing aids was associated with larger map DRs. Small map DRs were found across a range of age, age at onset, and duration of hearing loss. Cause of deafness did not appear to be related to map DRs.

Adolescent↗
PubMed1995

Differences in the capsaicin-induced dilation of arterioles and venules in rat striated muscle.

We previously found that capsaicin can dilate third-order arterioles in striated muscle by a mechanism that appears to involve release of endogenous calcitonin gene-related peptide (CGRP). Experiments were done to determine 1) whether capsaicin has similar effects on larger arterioles and venules and 2) whether relaxation involves endogenous CGRP and synthesis of endothelium-derived relaxing factor. In male Sprague-Dawley rats anesthetized with pentobarbital (50 mg/kg, i.p.), we examined responses of first- and second-order microvessels in the cremaster muscle using video microscopy. Addition of capsaicin (0.1 microgram/ml) to vessels constricted by norepinephrine (10(-7) M) dilated 1A's by 91% +/- 28%, 2A's by 113% +/- 18% 1V's by 11% +/- 6% and 2V's by 42% +/- 18%. Capsaicin in the presence of the specific CGRP receptor antagonist CGRP (8-37) caused an attenuated arteriolar dilation but had no significant venodilatory effect (1A's 29% +/- 18%, 2A's 55% +/- 14%, 1V's 7% +/- 3%, 2V's 16% +/- 3%). Pretreatment with N-nitro-L-arginine methyl ester (10(-4) M) did not prevent capsaicin-induced arteriolar dilation (A1's 118% +/- 11%; A2's 129 +/- 24%) but blocked capsaicin-induced venodilation (V1's constricted by 5% +/- 5%; V2's constricted by 2% +/- 6%). N-nitro-L-arginine methyl ester also blocked CGRP-induced dilation of both orders of venules, but not arterioles. These data suggest that capsaicin-induced dilation may involve synthesis of endothelium-derived relaxing factor in the venules but not in the arterioles.

Animals↗