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Biomedical subjects

G L Engelmann

Publications and source records attributed to G L Engelmann.

At least 19 recordsLinked to original sources
PubMed1996

In utero exposure to ethanol alters mRNA for insulin-like growth factors and insulin-like growth factor-binding proteins in placenta and lung of fetal rats.

Insulin-like growth factors I and II (IGF-I and IGF-II) play a role in regulating fetal growth and development. Their actions in target tissues are modulated in part by binding to IGF binding proteins 1 and 2 (IGFBP-1 and IGFBP-2). In this study, we examined the effect of fetal exposure to alcohol IGF-I and on IGF-II and IGFBP-1 and IGFBP-2 mRNA in placenta and fetal lung tissue. Timed-pregnant Sprague-Dawley dams were fed a diet consisting of 35% ethanol-derived calories [alcohol-fed (AF)], an Isocaloric diet with sucrose substituted for alcohol (pair-fed; PF), or ad libitum rat chow (CF). Alcohol feeding began on gestational age (G) 14. At G20, dams were killed, and we examined placenta and fetal lung for the steady-state levels of mRNA for IGF-1 and IGF-II and for IGFBP-1 and IGFBP-2. In all dams, body weight increased throughout gestation, and there were no differences between the three groups. At G20, the mean weight for the fetuses from the AF group was lower (p < 0.001) than the fetuses from the CF and PF groups. Steady-state mRNA levels were detected in fetal lung and in placentas by Northern-blot hybridization analysis and semiquantitated by slot-blot hybridization analysis. Multiple transcripts for IGF-I and IGF-II, 1.8 kb species for IG-FBP-1 and 1.6 kb species for IGFBP-2 were detected from total RNA isolated from the fetal lung and placenta, Slot-blot hydridization analysis of fetal lung RNA showed that IGF-I mRNA was significantly increased (p < 0.001) in AF males and females by 4.0 +/- 0.28-fold and by 3.25 +/- 0.2-fold, respectively. IGF-II transcript levels were not affected. IGFBP-1 and IGFBP-2 were increased in AF males, whereas only IGFBP-2 was increased in AF females. In the placenta, there was a significant increase in IGFBP-1 and IGFBP-2 transcripts [(p < 0.001) 1.75 +/- 0.5-fold and 3 +/- 0.53-fold increase, respectively]. No differences between the groups in serum levels of IGFBP-1 or -2 were detected when measured by Western-blot analysis. The increased gene expression for IGFBPs within fetal lung and placenta may decrease bioavailability of locally synthesized, IGFs that may contribute to the fetal growth retardation observed in this model system.

Animals↗
PubMed1995

Stimulation of a Ca(2+)-calmodulin-activated histone 3 arginine kinase in quiescent rat heart endothelial cells compared to actively dividing cells.

A Ca(2+)-calmodulin-activated histone 3 kinase was partially purified from nuclear extracts of dividing and quiescent rat heart endothelial cells. The histone 3 phosphorylating activity was 20-100-fold higher in quiescent than in dividing cells. Base hydrolysis followed by amino acid analysis revealed that histone 3 was phosphorylated on arginine. Further investigations were conducted to determine whether phosphorylation of histone 3 also occurred in vivo. Cells were incubated for 3 h in a phosphate-free medium supplemented with [32P]phosphoric acid. It was observed that the nuclear content of arginine-phosphorylated histone 3 was considerably higher in quiescent than in dividing rat heart endothelial cells. The histone 3 arginine kinase is a component of a complex containing a Ca(2+)-dependent calmodulin-binding protein of apparent molecular mass of 85 kDa. Using polyclonal antibodies to an 85-kDa protein, also the major Ca(2+)-dependent calmodulin-binding component of the histone 3 arginine kinase from calf thymus, an immunoreactive protein of identical apparent molecular mass was found to be present in equal amounts both in dividing and quiescent cells. We propose that the 85-kDa protein is either the histone 3 arginine kinase or one of its subunits and that phosphorylation of histone 3 is involved with cell cycle exit in eukaryotes.

Animals↗
PubMed1995

Human thymic epithelial cells produce TGF-beta 3 and express TGF-beta receptors.

TGF-beta affects proliferation, differentiation and maturation of T cells; however, the effect of TGF-beta on thymic stromal cells has not been characterized. To better understand the role of TGF-beta in T cell development, we determined whether TGF-beta is present in the human thymus, and identified stromal cells that express TGF-beta receptors and respond to TGF-beta. We demonstrate that primary cultured human thymic epithelial cells (TEC) express TGF-beta 1, TGF-beta 2 and TGF-beta 3, as well as TGF-beta type I receptor (T beta RI) (ALK-5) and TGF-beta type II receptor (T beta RII) transcripts. In vitro, epidermal growth factor (EGF) increases transcript levels of TGF-beta 1, TGF-beta 3 and T beta RII, suggesting that EGF may modulate TGF-beta responses in TEC; however, TGF-beta 2 and T beta RI transcript levels were not affected. We also detect TGF-beta 3 and T beta RII protein in association with keratin-positive TEC in vitro and in vivo. TEC culture supernatants contain TGF-beta 3 as detected by Western blots and, upon heat and acid activation, display growth inhibitory activity on the CCL-64 cells that is neutralized by anti-TGF-beta mAb treatment. We further demonstrate that TGF-beta 1 increases leukemia inhibitory factor transcript levels in TEC, indicating that TEC express functional TGF-beta receptors. Thus, we have shown in the human thymus that TEC produce TGF-beta 3 and express T beta RI and T beta RII. The data suggest that TGF-beta is present in the human thymus and may indirectly affect T cell development by regulating TEC cytokine production.

Animals↗
PubMed1994

Characterization of the gap junction protein, connexin45.

Connexin45 is a gap junction protein which forms channels with unique characteristics. RNA blots demonstrated that connexin45 is expressed in a number of cell lines including WB, SK Hep1, BHK, A7r5, CLEM, and BWEM cells. Connexin45 was further studied in BWEM cells using specific affinity-purified antibodies directed against a synthetic peptide representing amino acids 285-298 of its sequence. Immunofluorescence experiments demonstrated that the BWEM cells expressed both connexin43 and connexin45 and that these connexins colocalized. Connexin45 polypeptide, immunoprecipitated from BWEM cells metabolically labeled with [35S]-methionine, consisted of a predominant 48 kD polypeptide. Connexin45 and connexin43 contained radioactive phosphate when immunoprecipitated from BWEM cells metabolically labeled with [32P]-orthophosphoric acid. This phosphate label was removed from connexin45 by alkaline phosphatase digestion. Treatment of BWEM cells with the tumor promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibited intercellular passage of microinjected Lucifer yellow. While TPA treatment induced phosphorylation of connexin43 in these cells, it reduced the expression of connexin45. Furthermore, the connexin45 expressed after TPA treatment was not phosphorylated. These results suggest that treatments which alter protein phosphorylation may regulate connexin43 and connexin45 in BWEM cells by different mechanisms.

Animals↗
PubMed1994

Coordinate TGF-beta receptor gene expression during rat heart development.

Transforming growth factor-beta (TGF-beta) has been implicated to participate in heart development. The receptors which transduce the signal(s) mediated by TGF-beta ligand binding have only recently been cloned. One of the most prominent effects of TGF-beta is inhibition of cell proliferation, a process that is tightly regulated during heart development. Using the developing rat ventricle as a model system, we have determined the steady state expression patterns for the Type I, II, and III TGF-beta receptors (TGF-beta Rs). Using RNA isolated from ventricular chambers on day 18 of gestation through the ninth postnatal week of age, we detected a modest increase in expression levels for Type I and Type III TGF-beta Rs. In contrast, steady state transcript levels for the Type II TGF-beta R showed a profound developmental increase from nearly undetectable levels at the fetal ages examined to high levels during the first postnatal week of age. Immunoelectron microscopic localization of Type II TGF-beta R confirmed that the 3-week-old ventricular myocyte, as well as nonmyocytes, contained immunoreactive material. Immunoreactivity was found at both the cell surface as well as intracellular compartment. Regional variations (right ventricle, left ventricle, or septum) in the expression pattern of several markers of heart development, but not the TGF-beta R's, were found in RNA obtained from 3-week-old postnatal animals. These data suggest that "downstream" effectors of TGF-beta-mediated stimulation are modulated in a developmental, regional-specific manner in the neonatal/mature myocardium by the level of bioactive TGF-beta.

Animals↗
PubMed1993

Formation of fetal rat cardiac cell clones by retroviral transformation: retention of select myocyte characteristics.

Ventricular myocyte (cardiomyocyte) growth is exquisitely regulated such that embryonic and fetal development are the primary periods of active cellular division. This report describes formation of three separate cardiomyocyte cell clones obtained by replication-defective retroviral (v/myc and v-H-ras) transformation of primary cultures of day-16 fetal rat cardiomyocytes. The cell clones do not spontaneously contract, yet they express several cardiac-specific (cardiac troponin-C, alpha-cardiac actin) and associated genes (Connexin 43, Early growth response gene-1) with stable expression of several genes determined through the 28th passage. None of these cell clones express skeletal muscle actin or the skeletal muscle regulatory gene MyoD1; yet all display ultrastructural and biochemical evidence of their cardiac muscle lineage. Molecular and biochemical studies of cardiac-specific gene regulation can be anticipated from the cell clones as it pertains to nuclear transcription factors and transient CAT-based reporter gene constructs. The formation of these cell clones will enable further studies of growth and development of this unique muscle cell population of the cardiovascular system to be performed at the cellular and molecular level.

Animals↗
PubMed1993

Coordinate gene expression during neonatal rat heart development. A possible role for the myocyte in extracellular matrix biogenesis and capillary angiogenesis.

OBJECTIVE: Neonatal heart development is a period of active extracellular matrix deposition and capillary angiogenesis which follows the cessation of ventricular myocyte proliferation. The aim was to determine whether coordinate expression of growth factors by the ventricular myocyte could function to inhibit myocyte proliferation directly as well as indirectly by paracrine stimulation of non-myocyte extracellular matrix deposition and capillary angiogenesis. METHODS: Immunohistochemistry and northern blot hybridisations were performed on ventricular samples from fetal to mature animals of the spontaneously hypertensive (SHR) and normotensive control Wistar Kyoto (WKY) strains. RESULTS: Ventricular expression of types I, III, and IV collagen genes reached their "maximum" within the first 2-3 postnatal weeks and then rapidly declined. Expression of TGF beta 3 and SPARC were found to precede and accompany the changes in extracellular matrix gene expression during this same developmental period. TGF beta 3 was immunolocalised to fetal cardiomyocytes with very limited expression in neonatal/adult non-myocytes. Associated with the neonatal expression of TGF beta variants, transcripts for the type 2 IGF receptor gradually declined over the first three postnatal weeks. Myocyte TGF beta gene expression, latent TGF beta release, and paracrine mechanisms of action could be facilitated by residual type 2 IGF receptor expression to help mediate stimulation of non-myocyte extracellular matrix synthesis and deposition. CONCLUSIONS: Expression of select growth factors, growth factor receptors, and components of the extracellular matrix appear to be highly coordinated during ventricular remodelling which occurs during neonatal heart development. A paradigm is presented which integrates the expression patterns of various myocyte derived stimuli and their postulated impact on formation of the structural components of the neonatal heart by modulation of myocyte and non-myocyte cell types.

Animals↗
PubMed1993

Acidic fibroblast growth factor and heart development. Role in myocyte proliferation and capillary angiogenesis.

Proliferative growth of the ventricular myocyte (cardiomyocyte) is primarily limited to fetal and early neonatal periods of development. In concert with the neonatal "transition" from proliferative to hypertrophic growth, ventricular remodeling of the nonmyocyte compartment is characterized by increased extracellular matrix synthesis/deposition and capillary angiogenesis. A role for locally generated and bioactive ventricular acidic fibroblast growth factor (aFGF) in these processes is proposed and substantiated by the following: 1) colocalization of aFGF peptide and fibroblast growth factor receptor (flg) transcripts to the developing fetal cardiomyocyte by immunohistochemistry, immunoelectron microscopy, and in situ hybridization, 2) continued localization of aFGF peptide and transcripts to the neonatal/mature cardiomyocyte, and 3) localization of flg immunoreactivity and transcripts to specific neonatal ventricular nonmuscle cell types. Specific ventricular cell types at distinct developmental stages appear to be responsive to ventricular myocyte-derived aFGF (myocytes in the fetal heart and nonmyocytes/endothelial cells in the neonatal heart). These data indicate that expression of aFGF and one of its receptors (flg) are most pronounced in the fetal to early neonatal ventricle, the presence of both suggesting an autocrine/paracrine growth regulatory function. As the animal matures, ventricular capillary angiogenesis may be facilitated by "release" of cardiomyocyte-derived fibroblast growth factors into the surrounding extracellular space/matrix functioning as a "paracrine" angiogenic stimuli. Therefore, the results of our study suggest that myocyte-derived aFGF may function to increase the fetal ventricular cardiomyocyte population in absolute number as well as to facilitate the subsequent increase in capillary angiogenesis that occurs during cardiomyocyte maturation and ventricular remodeling.

Animals↗
PubMed1993

Regulation of procollagen metabolism in the pressure-overloaded rat heart.

To determine the molecular events responsible for the disproportionate accumulation of myocardial fibrillar collagens during sustained hypertension, we examined the in vivo rate of procollagen synthesis, collagen accumulation, and intracellular procollagen degradation 1-16 wk after abdominal aortic banding in young rats. These measurements were correlated with tissue mRNA levels for type I and type III procollagen polypeptides. Banded animals developed moderate, sustained hypertension and mild left ventricular hypertrophy. Increased type III procollagen mRNA levels were detected early after banding and persisted for the entire observation period. Disproportionate collagen accumulation without histological evidence of fibrosis was noted within 1 wk after hypertension induction. Fibrillar collagen accumulation at this time point resulted not from a major increase in procollagen synthesis, but rather a marked decrease in the rate of intracellular procollagen degradation. Interstitial fibrosis, however, was observed 16 wk after banding. Type I procollagen mRNA levels were increased six-fold, but only after 16 wk of hypertension. These results correlated well with the results of in vivo procollagen synthesis experiments at 16 wk, which demonstrated a threefold increase in left ventricular procollagen biosynthesis. We conclude that pretranslational as well as posttranslational mechanisms regulate fibrillar collagen deposition in the myocardial extracellular matrix during sustained hypertension.

Animals↗
PubMed1993

Acute morphological effects of cocaine on rat cardiomyocytes.

The cardiovascular actions of cocaine in vivo are varied and often antagonistic. Cocaine produces excitatory sympathomimetic effects by interfering with re-uptake of norepinephrine at adrenergic nerve terminals. However, the local anaesthetic properties of cocaine exert depressant effects on the myocardium. In an attempt to differentiate the direct effects of cocaine from the indirect sympathomimetic effects on the myocardium, primary cultures of neonatal rat cardiomyocytes were established under serum-free conditions and exposed to cocaine and/or norepinephrine. After 36-48 h in culture, spontaneously contracting cells were treated with cocaine (10-1,000 micrograms/ml) and contractile rate (beats/min) quantitated, after which the cells were processed for ultrastructural examination. The contractile rate was reduced at all dosages with nearly 80% reduction at the highest concentration studied. Recovery of beating rate was observed 24 h after removal of cocaine. Pronounced cytoplasmic vacuolation of the cells occurred at concentrations > or = 100 micrograms/ml. Ultrastructural examination revealed extensive myofibrillar disruption, membrane damage, and a near complete loss of organized sarcomeres. Nuclear morphology remained unaffected. Within 24 h after removal of cocaine from the medium, myocytes recovered their characteristic cytoplasmic architecture, indicative of sarcomere reassembly. The results observed in response to cocaine were distinctly different from the response to norepinephrine. In these myocytes, the contractile rate was enhanced twofold and morphological damage was not observed. These findings suggest that cocaine can directly alter myocardial morphology independent of its sympathomimetic effects.

Animals↗
PubMed1992

Transforming growth factor-beta 1 in heart development.

Defined biochemical stimuli regulating neonatal ventricular myocyte (cardiomyocyte) development have not been established. Since cardiomyocytes stop proliferating during the first 3-5 days of age in the rodent, locally generated 'anti-proliferative' and/or differentiation signals can be hypothesized. The transforming growth factor-beta (TGF-beta) family of peptides are multifunctional regulators of proliferation and differentiation of many different cell types. We have determined in neonatal and maturing rat hearts that TGF-beta 1 gene expression occurs in pups of both normotensive (Wistar Kyoto, WKY) and hypertrophy-prone rats (spontaneously hypertensive, SHR). TGF-beta 1 transcript levels were readily apparent in total ventricular RNA from SHR pups within 1 day of age and elevated in 3-7 day old WKY and SHR hearts when cardiomyocyte proliferation indices are diminished. TGF-beta 1 transcript levels remain at a 'relatively' high level throughout maturation and into adulthood in both strains. Further, TGF-beta 1 transcripts were localized to cardiomyocytes of neonatal rat ventricular tissue sections by in situ hybridization. Immunoreactive TGF-beta was co-localized to the intracellular compartment of neonatal cardiomyocytes at the light and electron microscopic level. In vitro analysis using primary cultures of fetal and neonatal cardiomyocytes indicated that TGF-beta s inhibit mitogen stimulated DNA synthesis and thymidine incorporation. From these data, we propose that locally generated TGF-beta s may act as autocrine and/or paracrine regulators of cardiomyocyte proliferation and differentiation as intrinsic components of a multifaceted biochemical regulatory process governing heart development.

Animals↗
PubMed1992

Contractile arrest accelerates myosin heavy chain degradation in neonatal rat heart cells.

Mechanical forces influence the growth and metabolism of a variety of cells, including cultured neonatal rat ventricular myocytes. To determine whether mechanical activity affected the synthesis and turnover of myosin heavy chain (MHC) in these striated muscle cells, MHC fractional degradative rates were measured in spontaneously beating cells and in arrested myocytes in which contractile activity was prevented by L-channel blockade (with verapamil, nifedipine, nisoldipine, and diltiazem) or K+ depolarization. MHC degradative rates were measured as the difference between rates of MHC synthesis and accumulation and in pulse-chase biosynthetic labeling experiments. Both methods indicated that contractile arrest markedly increased MHC degradation. Contractile arrest produced by L-channel blockade accelerated MHC degradation to a greater extent than K+ depolarization. The signal transduction pathway linking contractile activity to alterations in MHC degradation did not involve protein kinase C (PKC), because MHC degradation was unaffected by activating PKC in arrested cells or inhibiting PKC in spontaneously beating cells. Chloroquine and E-64 did not suppress the accelerated MHC degradation, suggesting that the rate-limiting step in MHC turnover occurred before degradative processing by cellular proteinases. Using a computer simulation, we hypothesize that the rate-limiting step in MHC turnover preceded (or was coincident with) MHC release from thick filaments. Thus mechanical forces may influence MHC half-life by regulating the rate of myosin disassembly.

Animals↗
PubMed1991

Role of transforming growth factor-beta 1 in regulation of hematopoiesis.

The data presented above suggest that one possible clinical use of TGF-beta would be to protect the bone marrow from the effects of myelosuppressive chemotherapeutic drugs by preventing entry or removing primitive stem cells from the cell cycle. It may also have the additional benefit of reducing the drug-induced neutrophil nadir by stimulating granulopoiesis. The availability of large quantities of recombinant TGF-beta will allow study of the pharmacokinetics with different routes of administration, dosage effects, and details of the pleiotropic effects on other cell systems. Experiments are in progress to determine whether TGF-beta will allow the delivery of higher amounts or more frequent doses of chemotherapeutic drugs and thus allow increased antitumor efficacy in tumor-bearing animals.

Animals↗
PubMed1991

Contractile activity modulates myosin heavy chain-beta expression in neonatal rat heart cells.

To determine whether spontaneous contractile activity affected the expression of myosin heavy chain isoenzymes in cultured neonatal rat heart cells, ventricular myocytes were isolated from 2-day-old rat pups by collagenase digestion and cultured for 24-96 h in the presence and absence of verapamil (10 microM), KCl (50 mM), or dihydropyridine receptor antagonists that produced contractile arrest. Inhibition of spontaneous contractile activity was associated with significant reductions in total myosin heavy chain (MHC) content and synthetic rates. Electrophoretic analysis of MHC isoenzymes indicated that MHC-beta protein rapidly disappeared from arrested cells, whereas MHC-alpha isoenzyme levels were less affected. In association with these protein changes, mRNA transcript levels for MHC-beta were markedly reduced in quiescent cells, whereas mRNA transcript levels for several other contractile protein genes were relatively less affected. Inhibition of contractile activity and MHC-beta expression were reversible upon removal of the arresting agents. Furthermore, the decrease in MHC-beta mRNA levels in arrested myocytes could be prevented by direct activation of protein kinase C with phorbol 12-myristate 13-acetate (without restoration of contractile activity). Conversely, MHC-beta mRNA levels in beating cells were reduced by treatment with staurosporine (a selective protein kinase C inhibitor). Thus contractile arrest (produced by either L-channel blockade or membrane depolarization) inhibited the accumulation of MHC-beta in cultured neonatal rat heart cells via a pretranslational mechanism. These effects may occur in response to the modulation of signaling system(s) involving mechanical "stretch" transduced via protein kinase C.

Animals↗
PubMed1989

Argon ion laser-excited autofluorescence in normal and atherosclerotic aorta and coronary arteries: morphologic studies.

Argon ion laser-excited autofluorescence was studied in unstained frozen sections of 47 normal and atherosclerotic human aortas and coronary arteries by means of a bright-field microscope modified for fluorescence microscopy with 476 nm argon ion laser epillumination, and compared to morphology in serial sections stained with H & E, Movat pentachrome, and oil red O. Normal artery autofluorescence correlated morphologically with the structural protein fibers elastin and collagen in the intima, media, and adventitia. Atherosclerotic plaque autofluorescence correlated morphologically with lipid or calcified deposits in the atheroma core. The autofluorescence of these deposits differed from that of elastin and collagen in distribution, intensity, and color, and increased with the severity of the plaque. We conclude that argon ion laser-excited autofluorescence in normal and atherosclerotic arteries correlates with morphology and has diagnostic potential in laser angiosurgery.

Adult↗
PubMed1989

Insulin-like growth factors and neonatal cardiomyocyte development: ventricular gene expression and membrane receptor variations in normotensive and hypertensive rats.

Defined factors regulating or influencing mammalian ventricular myocyte (cardiomyocyte) development are not known at this time. During early neonatal ventricular growth, cardiomyocytes begin a 'transition phase' of development toward cellular maturation (hypertrophy) that entails terminal proliferation and cellular binucleation. Insulin-like growth factor-I and -II (IGFs) are believed to play a major role in mammalian postnatal and fetal growth, possibly functioning in local environments which facilitate autocrine or paracrine tissue growth characteristics. Therefore, we examined the expression of the IGF genes and their corresponding membrane receptors in ventricles of normotensive and spontaneously hypertensive (SHR) rat pups during the first 7-14 days of age. We have determined: (1) by receptor crosslinking that neonatal ventricular membranes possess type 1 and type 2 IGF receptors; (2) by receptor binding analysis that type 1 IGF receptor concentration is elevated between days 1-7 in the SHR and shows an age-related decline in concentration and an increase in affinity in both strains; (3) by Northern blot analysis that neonatal rat ventricular tissue expresses primarily IGF-II RNA transcripts of 3.6, 2.3 and 1.7 kilobases (kb) in size, with low levels of IGF-I transcripts detected; (4) by slot-blot hybridization that SHR ventricles contain higher levels of IGF-II transcripts at 3 days of age; and (5) localized the IGF transcripts to ventricular myocytes by tissue in situ hybridization. These observations support a role for cardiomyocyte-produced IGFs that may be locally produced and act in an autocrine or paracrine fashion to modulate cardiomyocyte growth and maturation in the developing rat heart. Because both IGF receptor and IGF RNA transcript parameters differed in SHR hearts, genetically predisposed to hypertrophy, a potentially important biochemical alteration may be associated with the fetal/neonatal growth abnormalities of the developing heart in this rat strain.

Animals↗
PubMed1989

Cocaine-induced small vessel spasm in isolated rat hearts.

Cocaine abuse has been associated with pathologic cardiovascular events including acute myocardial infarction (AMI) and sudden death. Although coronary vasospasm has been proposed as a possible mechanism, the ability of cocaine to induce coronary spasm has not been conclusively demonstrated. In these studies, isolated rat hearts were perfused with cocaine (100 micrograms to 500 micrograms/ml) for 1 minute, perfusion-fixed with glutaraldehyde, and histologically assessed for evidence of coronary spasm through light and electron microscopy. Light micrographs revealed that cocaine induced spasm in coronary arterioles up to 65 microns in diameter, whereas larger caliber vessels did not constrict. Ultrastructurally, vacuolation was observed in the endothelial and smooth muscle cells of constricted arterioles. Endothelial integrity was maintained and interendothelial junctions remained intact. Morphologic evidence of constriction was supported by data obtained from Langendorff-heart preparations in which cocaine reduced myocardial flow rate under constant pressure conditions and increased aortic perfusion pressure under constant flow conditions. Spasm induced by cocaine was prevented by the calcium entry blocker nitrendipine, but not by phentolamine, an alpha-adrenergic antagonist. The finding of small vessel spasm in this study may explain the significant number of clinical cases of cocaine-associated AMI in which the main coronary arteries appear angiographically normal.

Animals↗