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O Kohmoto

Publications and source records attributed to O Kohmoto.

At least 37 records · Page 2Linked to original sources
PubMed1994

Nitric oxide-mediated effects of interleukin-6 on [Ca2+]i and cell contraction in cultured chick ventricular myocytes.

Cytokines have significant roles in some cardiovascular disorders, but direct myocardial effects of cytokines remain to be elucidated. In the present study, we examined both the early and delayed effects of interleukin-6 (IL-6) on cultured chick embryo ventricular myocytes. Exposure of these cells to human recombinant IL-6 significantly decreased peak systolic [Ca2+]i (71.0 +/- 0.6% of the control value) and the amplitude of cell contraction (66.0 +/- 7.4% of the control value) within a few minutes. Pretreatment with NG-monomethyl-L-arginine (L-NMMA) or methylene blue completely inhibited the IL-6-induced early changes. Subsequent addition of L-arginine reversed the effects of L-NMMA. The levels of cGMP were significantly increased after 30 minutes of exposure to IL-6 (134.4 +/- 9.1% of the control value). Pretreatment with L-NMMA or EGTA significantly inhibited the IL-6-induced early elevation of cGMP. These results suggest that IL-6 acutely decreases intracellular Ca2+ transients and depresses cell contraction by nitric oxide (NO)-cGMP-mediated pathway. Therefore, IL-6 may enhance the Ca(2+)-dependent constitutive NO synthase activity in cardiac myocytes. On the other hand, 24-hour exposure to IL-6 also increased the levels of cGMP (159.0 +/- 22.8% of the control value) regardless of pretreatment with EGTA. These delayed increases in cGMP were also shown to be coupled with decreases in intracellular Ca2+ transients and the amplitude of cell contraction. Thus, IL-6 may induce Ca(2+)-independent NO synthase in cardiac myocytes. Together with the previous reports that have suggested the possible roles of IL-6 in myocardial stunning or endotoxic shock, this negative inotropic effect of IL-6 may contribute to these clinical settings.

Amino Acid Oxidoreductases↗
PubMed1993

Effects of a nonpeptide angiotensin II receptor antagonist (CV-11974) on [Ca2+]i and cell motion in cultured ventricular myocytes.

We studied the effects of angiotensin II and CV-11974 (a newly synthesized angiotensin II receptor antagonist) on cell contraction and [Ca2+]i in cultured neonatal rat ventricular myocytes. Exposure of these cells to 10 nM angiotensin II significantly decreased peak systolic cell position (60.1 +/- 3.3% of the control, P < 0.01) and peak systolic [Ca2+]i (from 1111 +/- 250 to 572 +/- 143 nM, P < 0.05) within 60 s. Pretreatment of ventricular myocytes with CV-11974 (10-100 nM) completely suppressed the angiotensin II-induced changes in peak systolic cell position and [Ca2+]i. These results suggest that CV-11974 inhibits cardiac angiotensin II receptors.

Angiotensin Receptor Antagonists↗
PubMed1993

Variable effects of endothelin-1 on [Ca2+]i transients, pHi, and contraction in ventricular myocytes.

We examined the effects of endothelin-1 (ET-1) on intracellular free calcium concentration ([Ca2+]i) transients, intracellular pH (pHi), and cell contraction in both embryonic and neonatal as well as in adult ventricular myocytes. Exposure of chick ventricular myocytes to ET-1 (10 nM) significantly decreased both peak systolic and end-diastolic [Ca2+]i (from 949 +/- 43 to 628 +/- 59 nM and from 230 +/- 13 to 162 +/- 8 nM, respectively; P < 0.05, n = 12). The amplitude of cell contraction was also decreased during exposure to 10 nM ET-1 (81.7 +/- 1.2% of control, P < 0.01, n = 12). Exposure to 10 nM ET-1 slightly decreased pHi (-0.055 +/- 0.020 U; P < 0.05). Exposure of cultured neonatal rat ventricular myocytes to ET-1 (10 nM) produced similar effects. Responses of adult rabbit ventricular myocytes to ET-1 were dramatically different from those of embryonic or neonatal ventricular myocytes. Exposure to 10 nM ET-1 increased the amplitude of cell contraction to 159 +/- 32% of control (P < 0.01) without an increase in [Ca2+]i transients. ET-1 also increased pHi (+0.081 +/- 0.047 U; P < 0.01). These results indicate that ET-1 produces a negative inotropic effect by decreasing [Ca2+]i transients and induces a slight intracellular acidosis in immature ventricular myocytes. However, ET-1 causes a positive inotropic effect in adult ventricular myocytes via an intracellular alkalinization, rather than by an increase in the [Ca2+]i transient. Thus the response of myocytes to vasoactive peptides may vary with development and/or species.

Aging↗
PubMed1992

Effects of new intravascular contrast agents on [Ca2+]i transients and contraction in cultured ventricular myocytes.

We examined the effects of four kinds of intravascular contrast agents (amidtrizoic acid, iohexol, iopamidol, and ioxaglic acid) on [Ca2+]i transients (indo-1 fluorescence) and cell contraction (video motion analyzer), using cultured chick embryo ventricular myocytes. Exposure of ventricular myocytes to amidtrizoic acid (a conventional contrast agent) reduced the [Ca2+]i transients and the sensitivity of the contractile elements to [Ca2+]i. Ioxaglic acid (a low osmotic contrast agent) also reduced the [Ca2+]i transients, but did not significantly change the sensitivity of the contractile elements to [Ca2+]i. Neither iohexol nor iopamidol (nonionic contrast agents) reduced the [Ca2+]i transients, but both significantly decreased the sensitivity of the contractile elements to [Ca2+]i. A marked negative inotropic effect of amidtrizoic acid was caused by both calcium binding and hypertonicity. The less marked depression of contractility produced by ioxaglic acid is possibly the result of calcium binding, but is not caused by hypertonicity. The negative inotropism produced by nonionic contrast agents (iohexol and iopamidol) was due to hypertonicity, but not due to alterations in the [Ca2+]i transients. Exposure of ventricular myocytes to nonionic contrast agents (iohexol and iopamidol) slowed decay in the [Ca2+]i transients with increased end-diastolic [Ca2+]i. After washing out the nonionic contrast agents, these parameters returned to control levels. On the other hand, exposure to amidtrizoic acid decreased end-diastolic [Ca2+]i without changing decay time in the [Ca2+]i transients. After washing out amidtrizoic acid, there was a prolongation of half decay time in [Ca2+]i transients with a significant increase in end-diastolic [Ca2+]i and cell position. Diastolic dysfunction just after washout of amidtrizoic acid was possibly caused by an increase in [Na+]i due to sodium influx during exposure to the contrast agent.

Animals↗
PubMed1992

Effects of a nonpeptide vasopressin antagonist (OPC-21268) on cytosolic Ca2+ concentration in vascular and cardiac myocytes.

A selective V1 antagonist, 1-(1-[4(3-acetylaminopropoxy)benzoyl]-4-piperidyl)-3,4-dihydro-2(1 H)- quinolinone (OPC-21268), which is nonpeptide and orally effective, has been recently synthesized. We studied the effects of vasopressin and OPC-21268 on cell contraction with a video motion detector and cytosolic Ca2+ concentration ([Ca2+]i) by using indo-1 in cultured rat vascular smooth muscle cells and cultured chick embryo ventricular myocytes. Exposure of cultured vascular smooth muscle cells to vasopressin (1-100 nM) dose-dependently produced an initial transient increase (from control level [Ca2+]i of 133.6 +/- 10.9 nM to peak [Ca2+]i of 842.7 +/- 172.8 nM at 100 nM vasopressin, p less than 0.01) and then a small sustained increase in [Ca2+]i. After pretreatment of vascular smooth muscle cells with 1 microM OPC-21268, the effects of 100 nM vasopressin on [Ca2+]i were abolished. Exposure of ventricular myocytes to 100 nM vasopressin slightly but significantly decreased peak systolic cell position (-8.7 +/- 3.7%, p less than 0.05) and also produced reductions in peak systolic [Ca2+]i (from 962.2 +/- 76.4 to 751.2 +/- 70.5 nM, p less than 0.01) within 30 seconds. Pretreatment of ventricular myocytes with OPC-21268 (1 microM) completely suppressed vasopressin-induced changes in peak systolic cell position and [Ca2+]i. These results suggest that vasopressin may increase vascular tone and may also cause a direct negative inotropic effect via V1 receptors and that this orally active V1 antagonist (OPC-21268) may have potential clinical usefulness.

Animals↗
PubMed1992

Cellular mechanisms for synthesis and secretion of atrial natriuretic peptide and brain natriuretic peptide in cultured rat atrial cells.

To investigate the cellular mechanism for the synthesis and secretion of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), we examined the effects of vasoactive agents on the secretion rates and gene expression of ANP and BNP in cultured rat atrial cells. Endothelin (10(-7) M, +61%), 12-O-tetradecanoylphorbol 13-acetate (TPA, 10(-6) M, +62%), the calcium ionophore A23187 (10(-6) M, +95%), and Bay K 8644 (10(-6) M, +34%) (p < 0.05 each) all increased the secretion of ANP into the culture media in a dose-dependent fashion. On the other hand, endothelin (10(-7) M, +57%) and TPA (10(-6) M, +55%) (p < 0.01 each) increased the secretion of BNP in a dose-dependent manner, whereas A23187 (10(-6) M, -45%, p < 0.001) suppressed the secretion of BNP in a dose-dependent manner, and Bay K 8644 caused no significant effects on BNP secretion. The molecular forms of intracellular ANP were exclusively gamma-ANP, whereas those of BNP were gamma-BNP and its carboxy terminal 45-amino-acid peptide, BNP-45. The ratio of media to cell contents was much higher in BNP than in ANP. Northern blot analysis revealed that both ANP mRNA and BNP mRNA levels were significantly increased by 10(-7) M endothelin (ANP mRNA, +52%; BNP mRNA, +36%; p < 0.05 each) and 5 x 10(-5) M 1-oleoyl-2-acetylglycerol (ANP mRNA, +296%; BNP mRNA, +133%; p < 0.01 each) but not by 10(-6) M A23187. Thus, the secretion of ANP is stimulated by both the elevation of [Ca2+]i and the activation of protein kinase C, whereas its synthesis is increased mainly by the activation of protein kinase C. The synthesis and secretion of BNP are augmented by the activation of protein kinase C rather than the elevation of [Ca2+]i. Furthermore, the processing and secretion of ANP and BNP may be regulated in different manners.

Animals↗
PubMed1991

Endothelin-1 secretion from cultured rabbit gastric epithelial cells.

It has been shown that endothelin-1 (ET-1) is synthesized in various extraendothelial tissues. Although ET-1 has been reported to have potent ulcerogenic action in the stomach, the synthesis and physiological roles of ET-1 in the gastric mucosa are poorly understood. The aim of the present study was to investigate whether or not cultured gastric epithelial cells secrete ET-1 and possess autocrine functions. Gastric epithelial cells from rabbits were cultured in medium supplemented with 10% FBS after isolation. ET-1 was extracted by C18 columns from serum-free culture media and measured by radioimmunoassay (RIA). Effects of ET-1 on the intracellular concentration of calcium of the cultured cells were examined with Indo-1. Prostaglandin E2 (PGE2) was measured by RIA. Primary cultures of gastric epithelial cells were mainly composed of mucous cells. ET-1 was detected in the culture medium by RIA, and 70 pg/10(6) cells/24 h of ET-1 was secreted by cultured cells. Tumor growth factor-beta (4 ng/ml) and thrombin (8 U/ml) significantly increased ET-1 secretion. Exogenously administered ET-1 up to 10(-6) M neither modulated the intracellular calcium concentration nor affected PGE2 release by these cells. These results suggest that gastric mucous cells in culture secrete ET-1. Further studies are needed to explore the possible involvement of such paracrine function in the reported ulcerogenic action of ET-1.

Animals↗
PubMed1991

Mechanisms of reoxygenation injury in cultured ventricular myocytes.

To investigate factors contributing to reperfusion and reoxygenation myocardial injury, we exposed layers of cultured chick ventricular myocytes to severe hypoxia for up to 3 hours in the presence of 20 mM 2-deoxyglucose, zero glucose, and 5 mM pyruvate, and then exposed the myocytes to reoxygenation. Lactate dehydrogenase (LDH) release was moderately increased during 3 hours of hypoxia but was increased markedly during reoxygenation. Coincident changes in intracellular calcium concentration ([Ca2+]i) and cell motion were also measured during hypoxia and reoxygenation. During hypoxia, [Ca2+]i increased to more than 1 microM, and with reoxygenation, [Ca2+]i abruptly decreased slightly but remained elevated more than 1 microM. Cells developed a stable rigor after 30 minutes of hypoxia. Reoxygenation caused a marked hypercontracture within 5 minutes. Pretreatment of myocytes with either 2,3-butanedione monoxime, which inhibits Ca2(+)-dependent force development, or cyanide inhibited reoxygenation hypercontracture. LDH release after reoxygenation was also significantly reduced in the presence of 2,3-butanedione monoxime. Treatment of myocytes with superoxide dismutase and catalase during hypoxia also resulted in a decrease in LDH release during reoxygenation. We conclude that an abrupt increase in [Ca2+]i during reoxygenation does not account for reoxygenation injury. However, in the presence of elevated [Ca2+]i, reoxygenation and the resulting probable resynthesis of ATP causes [Ca2+]i-dependent myofilament crossbridge cycling, and the resulting hypercontracture contributes to myocyte damage. The generation of oxygen free radicals after reoxygenation also appears to contribute to cell injury in this system.

Adenosine Triphosphate↗
PubMed1991

Contributions of [Ca2+]i, [Pi]i, and pHi to altered diastolic myocyte tone during partial metabolic inhibition.

Ischemia may cause increased or decreased distensibility of the left ventricle, but the cellular mechanisms involved have not been clarified. We examined the possible contributions of changes in intracellular inorganic phosphate, pH, and Ca2+ concentrations to altered diastolic function in cultured myocytes subjected to partial metabolic inhibition. Paced cultured embryonic chick and adult rabbit ventricular myocytes superfused with 20 mM 2-deoxyglucose (2DG) exhibited an increase in end-diastolic intracellular free calcium concentration ([Ca2+]i) and an upward shift in end-diastolic cell position. These results indicate that glycolytic blockade increases diastolic and systolic calcium in paced ventricular myocytes, and that this elevated diastolic calcium influences the extent of diastolic relaxation. In contrast, paced ventricular myocytes superfused with 1 mM cyanide (CN) exhibited a similar increase in end-diastolic [Ca2+]i but a decrease in end-diastolic cell position and amplitude of motion. Although changes in ATP contents were similar in both groups (2DG, -29.9%; CN, -40.1%), alterations of intracellular pH and inorganic phosphate concentrations were different. In 2DG-treated cells, pHi did not decrease significantly (7.18 +/- 0.04 to 7.12 +/- 0.11, n = 14) but in the CN group it decreased markedly within 6 min (7.18 +/- 0.04 to 6.76 +/- 0.11, n = 11, P less than 0.01). Intracellular inorganic phosphate decreased slightly in the 2DG group (-14.8%, NS) but increased in cells exposed to CN (45.7%, P less than 0.02). We conclude that while a prominent increase in diastolic [Ca2+]i occurs in rapidly paced ventricular myocytes exposed to either inhibitors of glycolysis or oxidative phosphorylation, the effects of this increase in [Ca2+]i on diastolic distensibility may be influenced by intracellular accumulation of metabolites that decrease the sensitivity of myofilament to [Ca2+]i.

Animals↗
PubMed1990

Doppler echocardiographic-determined changes in left ventricular diastolic filling flow velocity during the lower body positive and negative pressure method.

Changes in parameters of left ventricular (LV) diastolic filling flow obtained with Doppler echocardiography during the lower body positive and negative pressure method were analyzed in 15 patients (12 with coronary artery disease and 3 with dilated cardiomyopathy). Lower body pressure was altered at 5 steps (+20, +10, 0, -20 and -40 mm Hg vs atmospheric pressure). Pulmonary capillary wedge pressure measured with a balloon-tipped catheter was changed proportionally with lower body pressure during the procedures (p less than 0.01). Mean systemic arterial pressure was changed slightly during lower body positive pressure and negative pressure of -40 mm Hg. Heart rate was almost unchanged except at lower body pressure of -40 mm Hg. The peak velocity of LV early diastolic filling flow was changed with pulmonary capillary wedge pressure in an almost parallel fashion during the procedures (p less than 0.01). The peak velocity of LV late diastolic filling flow showed smaller changes than that of early diastolic filling flow. Changes in pulmonary capillary wedge pressure correlated positively with changes in the peak velocity of LV early diastolic filling flow (r = 0.759, p less than 0.01), but not with changes in the peak velocity of LV late diastolic filling flow (r = 0.039, not significant) during lower body negative pressure of -20 mm Hg. These data suggest that left atrial pressure is one of the important determinants of LV early diastolic filling flow in this acute clinical setting and that LV late diastolic filling flow is less sensitive to changes in left atrial pressure than LV early diastolic filling flow.

Adult↗
PubMed1990

Activation of furosemide-sensitive K+ fluxes in myocytes by ouabain and recovery from metabolic inhibition.

Modulation of transsarcolemmal K+ flux mediated by the furosemide-sensitive K(+)-Cl- (or Na(+)-K(+)-Cl-) cotransport carrier was studied in cultured chick embryo ventricular cells. We defined at least three distinct K+ efflux pathways: 1) a Ba2(+)-sensitive efflux component, probably reflecting K+ movement through K+ channels; 2) a furosemide-sensitive component, reflecting K(+)-Cl- cotransport; and 3) a component insensitive to both Ba2+ and furosemide. With respect to K+ influx, there were 1) a ouabain-sensitive K+ uptake presumably mediated by Na(+)-K(+)-adenosinetriphosphatase and 2) a furosemide-sensitive K+ uptake. The effects of elevation of intracellular calcium concentration ([Ca2+]i) on Ba2+ and furosemide-sensitive K+ flux pathways were studied. Elevation of [Ca2+]i had minor effects on Ba2(+)-sensitive K+ flux. However, elevation of [Ca2+]i produced by exposure to ouabain for 60 min activated a furosemide-sensitive 42K+ efflux and a ouabain-resistant, furosemide-sensitive 42K+ influx. The activation of K+ influx, caused by an increase in [Ca2+]i, was completely inhibited by ATP depletion (produced by exposure to ouabain and metabolic inhibitors simultaneously) and was partially inhibited by the calmodulin inhibitor W7. Activation of the furosemide-sensitive K+ flux was also produced by washout of metabolic inhibitors, a condition in which ATP resynthesis occurs in the presence of an increased [Ca2+]i. Activation of furosemide-sensitive K+ fluxes by exposure to ouabain or washout of metabolic inhibitors caused a net K+ loss, which accounts in part for the cell shrinkage noted during recovery from metabolic inhibition in previous studies. These results suggest that [Ca2+]i and intracellular ATP concentration are important in the regulation of furosemide-sensitive K+ flux in these cells, perhaps via the involvement of a Ca2(+)-calmodulin-dependent protein kinase.

Adenosine Triphosphate↗
PubMed1990

Effects of intracellular acidosis on [Ca2+]i transients, transsarcolemmal Ca2+ fluxes, and contraction in ventricular myocytes.

We examined the effects of intracellular acidosis produced by washout of NH4Cl on [Ca2+]i transients (indo-1 fluorescence), cell contraction (video motion detector), and 45Ca and 24Na fluxes in cultured chick embryo ventricular myocytes. Exposure of cells to 10 mM NH4Cl produced intracellular alkalosis (pH 7.6), and subsequent washout resulted in a transient acidosis (pH 6.5). Exposure to 10 mM NH4Cl slightly decreased [Ca2+]i transients but increased the amplitude of cell contraction. Subsequent washout of NH4Cl initially increased diastolic [Ca2+]i and decreased the peak positive and negative d[Ca2+]i/dt, while the amplitude of cell contraction was markedly decreased. Subsequently, peak systolic [Ca2+]i increased with partial recovery of contraction. A similar increase in [Ca2+]i and decrease in contraction after washout of NH4Cl was observed in single paced adult guinea pig ventricular cells. Acidosis decreased 45Ca uptake by sarcoplasmic reticulum vesicles isolated from chick embryo ventricle. However, the [Ca2+]i increase caused by intracellular acidosis was also observed in the presence of 10 mM caffeine, suggesting that altered sarcoplasmic reticulum handling of calcium is not the only mechanism involved. Intracellular acidosis only slightly increased total 24Na uptake under these conditions, an effect resulting from the combination of a stimulation of amiloride-sensitive sodium influx (Na(+)-H+ exchange) and inhibition of sodium influx via Na(+)-Ca2+ exchange, manifested by a significant decrease in 45Ca efflux. Further support for a lack of involvement of an increased [Na+]i in the observed increase in [Ca2+]i during acidosis was low-sodium, nominal 0-calcium extracellular solution, an experimental condition that minimizes the possible effects of Na(+)-H+ exchange and Na(+)-Ca2+ exchange. We conclude that the [Ca2+]i increase caused by intracellular acidosis in cultured ventricular cells is primarily due to changes in [Ca2+]i buffering and [Ca2+]i extrusion, rather than to an increase in transsarcolemmal calcium influx. Intracellular acidosis also markedly decreases the sensitivity of the contractile elements to [Ca2+]i in cultured chick embryonic and adult guinea pig ventricular myocytes.

Acidosis↗
PubMed1990

Significance of left atrial pressure and left ventricular relaxation as determinants of left ventricular early diastolic filling flow in man.

We analyzed the relationships among parameters of left ventricular (LV) early diastolic filling flow (EDF) obtained with pulsed Doppler echocardiography, mean pulmonary wedge pressure (PCWP) and the time constant of LV pressure fall calculated by either Weiss' (Tw) or Thompson's (Tb) method. PCWP correlated with the peak velocity (R) (r = 0.537, p less than 0.05), acceleration (Ac) (r = 0.545, p less than 0.05) and deceleration (Dc) (r = 0.606, p less than 0.01) of LVEDF. In contrast, Tb correlated only with the time to the peak of LVEDF (TPF) (r = 0.487, p less than 0.05), and Tw did not correlate with the Doppler-derived indices significantly. After correcting for the effect of PCWP, significant partial correlations between R and Tw (r = -0.535, p less than 0.05), and between Ac and both Tw (r = -0.606, p less than 0.01) and Tb (r = -0.569, p less than 0.05) were found. Dc did not correlate with Tw or Tb. These results suggest that the level of left atrial pressure may mask the relationship between parameters of LVEDF and LV relaxation, and that the relations among these variables vary with individual indices of LVEDF.

Adult↗
PubMed1989

Detection of La3+ influx in ventricular cells by indo-1 fluorescence.

We exposed indo-1-loaded cultured embryonic chick ventricular cells to 0.03-1.0 mM extracellular lanthanum concentration ([La3+]o) and simultaneously measured cell contractile motion and the 410/480 nm fluorescence intensity ratio. After exposure to La3+, ventricular cells stopped contracting and relaxed within seconds, and the 410/480 fluorescence ratio increased. The increase in the 410/480 signal was related to [La3+]o but was not affected by short exposures to zero extracellular calcium concentration ([Ca2+]o) or caffeine, suggesting that the fluorescence was not caused by a La3+-induced increase in intracellular calcium concentration ([Ca2+]i) but rather to increased intracellular lanthanum concentration ([La3+]i). In vitro studies confirmed that indo-1 fluorescence was sensitive to La3+. The increase in [La3+]i in 0.1 mM [La3+]o was directly related to intracellular sodium concentration ([Na+]i), suggesting that La3+ entered cells via Na+-La3+ exchange. In contrast to ventricular cells, which have a functionally distinct Na+-Ca2+ exchange system, exposure of indo-1-loaded cultured bovine endothelial cells to La3+ failed to produce an increase in [La3+]i. These results indicate that exposure of ventricular cells to 0.1-1.0 mM [La3+]o results in a [La3+]i greater than 250 nM within 1 min. Therefore, changes in myocardial 45Ca2+ fluxes and contents induced by La3+ cannot be ascribed solely to extracellular La3+ effects.

Animals↗
PubMed1989

Mechanism of protective effects of Ca++ channel blockers on energy deprivation contracture in cultured ventricular myocytes.

To examine mechanisms of the protective effects of Ca++ channel blockers on energy deprivation contracture, we measured cystolic calcium ion concentration ([Ca++]i) (Indo-1 fluorescence), development of contracture (video motion detector) and ATP contents during exposure of cultured chick embryo ventricular cells to 1 mM cyanide (CN) and 20 mM 2-deoxyglucose (2-DG). The time periods required for [Ca++]i to reach 50% of [Ca++]i transient ([Ca++]i-50) and contracture were determined after exposure to 1) CN + 2-DG alone, 2) CN + 2-DG simultaneous with 1 microM verapamil (V-sim) and 3) verapamil followed by CN + 2-DG (V-pre). Time periods required to reach [Ca++]i-50 under these conditions were 4.2 +/- 0.4 min (CN + 2-DG alone), 3.8 +/- 0.4 min (NS vs. CN + 2-DG alone) (V-sim) and 6.4 +/- 1.1 min (P less than .05 vs. CN + 2-DG alone) (V-pre), respectively. Time periods required for contracture development were 4.4 +/- 0.3 min (CN + 2-DG alone), 4.4 +/- 0.6 min (NS vs. CN + 2-DG alone) (V-sim) and 9.3 +/- 1.2 min (P less than .05 vs. CN + 2-DG alone) (V-pre). Three minutes after metabolic inhibition, ATP contents declined from 32.3 +/- 0.7 nmol/mg of protein to 4.2 +/- 1.0 in CN + 2-DG alone, to 4.5 +/- 0.9 (NS vs. CN + 2-DG alone) with V-sim and to 8.3 +/- 2.2 (P less than .05 vs. CN + 2-DG alone) with V-pre.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1988

Estimation of the secretion rate of atrial natriuretic peptide from the coronary sinus in coronary artery disease.

Although atrial natriuretic peptide (ANP) is known to be secreted through the coronary sinus into the systemic circulation, its actual secretion rate has not been thoroughly investigated. The immunoreactive ANP concentrations in plasma samples from the ascending aorta and coronary sinus in 11 patients with the coronary artery disease were measured and the coronary sinus flow rate using the continuous thermodilution method was simultaneously determined at the time of sampling. These variables were also determined during the intravenous infusion of synthetic alpha-human ANP at 0.025 microgram/kg.min in 7 of the 11 patients. In the basal state, the plasma concentration of ANP was 61 +/- 6 (standard error) pg/ml in the aorta and 541 +/- 40 pg/ml in the coronary sinus, and the coronary sinus flow index was 57.3 +/- 12.3 ml/min.m2. Thus, the secretion rate of ANP was determined to be 14.4 +/- 2.8 ng/min.m2. The secretion rate of ANP correlated significantly with the plasma concentration of ANP in the aorta (r = 0.65, p less than 0.05). The ANP infusion, which decreased pulmonary artery wedge pressure from 8.0 +/- 0.6 to 6.3 +/- 0.4 mm Hg (p less than 0.01), elevated the plasma concentrations of ANP in the aorta and coronary sinus by 701% (p less than 0.001) and 33% (p less than 0.05), respectively, and decreased the secretion rate of ANP by 40% (p less than 0.05). These results suggest that the circulating plasma concentration of ANP may reflect the secretion rate of ANP and that an increase in circulating ANP directly or indirectly reduces ANP secretion.

Aorta↗
PubMed1988

Effects of contrast media on calcium transients and motion in cultured ventricular cells.

To investigate the mechanisms of the negative inotropic effects of contrast media, we superfused spontaneously contracting cultured chick embryo ventricular cells with Renografin-76 and iohexol (12% solutions), and hypertonic sucrose during simultaneous measurement of [Ca2+]i transients (indo-1) and motion (video-motion detector system). Exposure to contrast agents caused a significant reduction of contractility, with Renografin-76 having a much greater effect on amplitude of motion than iohexol. Renografin-76 significantly depressed [Ca2+]i transient amplitude, whereas iohexol had no effect. Addition of Ca2+ to correct for calcium binding by Renografin-76 completely reversed its depression of [Ca2+]i transients but only partially reversed the negative inotropic effects. Hypertonic sucrose caused a significant decrease in contraction amplitude, with no significant effects on [Ca2+]i transient amplitude. We conclude that the marked negative inotropic effect of Renografin-76 is caused by both calcium binding and hypertonicity. The less marked depression of contractility produced by iohexol likely is a result of hypertonicity and not caused by alteration of [Ca2+]i.

Animals↗