bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional vascular resistance vs. conductance: which index for baroreflex responses?
Authors: O'Leary D. S.
Published: December 2017

When large changes in baseline blood flow occur in regional vascular beds (i.e., in skeletal muscle between rest and dynamic exercise or in skin between normothermia and hyperthermia) opposite conclusions are often drawn regarding the magnitude of a given vasomotor response (such as baroreflex vasoconstriction during hypotension) using regional resistance versus conductance. This report analyzes the relationship between changes in regional resistance or conductance and the contribution of the responses in the maintenance of blood pressure. The main supposition is that the appropriate index of baroreflex responses should reflect the importance of the response in the maintenance of blood pressure. Through differential analysis of the relationship between changes in resistance and conductance on arterial pressure, it can be seen that in terms of resistance, the effect of a given change in resistance on arterial pressure is greatly dependent on the baseline level of resistance. For conductance, while a modest baseline effect exists when cardiac output changes markedly, at a constant cardiac output, the same change in regional conductance always causes the same change in arterial pressure regardless of the initial value of conductance. Conclusions drawn are that while neither resistance nor conductance is a perfect index of vasomotor responses, changes in conductance far better reflect the importance of the response in pressure regulation than do changes in regional resistance.
Alterations in cardiac parasympathetic function in aged rats
Authors: Ferrari A. U. , Daffonchio A. , Gerosa S. , Mancia G.
Published: December 2017

Aging impairs sympathetic and parasympathetic cardiac control. Although the reduced sympathetic responses are known to depend on an age-related cardiac beta-adrenoceptor dysfunction, the hypothesis of a parallel cardiac muscarinic receptor dysfunction underlying the reduced parasympathetic responses has never been tested. We therefore measured the bradycardic responses to graded electrical stimulations of the right efferent vagus and to graded bolus intravenous injections of acetylcholine in anesthetized, vagotomized rats of young (16 wk) and old (103 wk) age. Unexpectedly, the bradycardia was markedly larger (greater than 2-fold) in old than in young rats with both the electrical and the pharmacological stimulus. This indicates that at variance with its effects on beta-adrenergic receptor responsiveness, aging not only fails to impair but actually enhances cardiac muscarinic receptor responsiveness. It also suggests the more general conclusion that aging has complex and diversified effects rather than simply and uniformly depressing biological functions.
Diameter changes in arteriolar networks of contracting skeletal muscle
Authors: Dodd L. R. , Johnson P. C.
Published: December 2017

The effect of muscular contraction on vessel diameter was studied in the arteriolar network of the exteriorized cat sartorius muscle during normal and elevated vascular tone. Dilation during 4 Hz motor-nerve stimulation was proportionately greatest in the third-order (transverse) arterioles and in vessels immediately upstream and downstream (P less than 0.01). This pattern of dilation was maintained with increased contraction frequency (30 Hz) and during concurrent sympathetic nerve stimulation (8 Hz). The pattern of constriction with sympathetic nerve stimulation alone showed a similar trend with the greatest response in the third-order and adjacent vessels. A model developed to estimate the resistance distribution in the arteriolar network, using data from earlier micropressure and vascular architecture studies in the sartorius muscle, allowed calculation of the resistance change during muscle contraction and sympathetic stimulation. Model predictions indicate that the third-order and adjacent vessels are the greatest site of resistance with both normal and elevated vascular tone. Thus these vessels were the site of greatest resistance change during muscle contraction. The more proximal, arcade vessels made lesser contributions to overall resistance changes, whereas the most distal, fifth-, and sixth-order arterioles appear not to be important in this regard. These findings indicate the third-order, transverse, arterioles are of special importance in regulating blood flow in the sartorius muscle.
Activity of in vivo atrial and ventricular neurons in chronically decentralized canine hearts
Authors: Ardell J. L. , Butler C. K. , Smith F. M. , Hopkins D. A. , Armour J. A.
Published: December 2017

The spontaneous activity of 175 neurons located in the ventral right atrial and ventral interventricular ganglionated plexi was recorded in eight anesthetized dogs, the hearts of which were chronically decentralized at least 2 wk before recordings were made. Ganglia were subsequently identified anatomically in the immediate vicinity of the recording sites. Spontaneous activity was correlated with the cardiac cycle in 57% of the atrial and 62% of the ventricular neurons and with the respiratory cycle in 29% of the atrial and 28% of the ventricular neurons. Spontaneous cardiovascular-related activity was recorded when systemic arterial pressure was between 80 and 175 mmHg. The activity of 23 atrial and 15 ventricular neurons was altered when discrete regions of the heart were mechanically distorted by gentle touch. These data imply that cardiac ganglionated plexi contain afferent neurons that receive inputs from limited regions of the heart. The spontaneous activity generated by intracardiac neurons was not altered when extracardiac tissues were distorted. These results demonstrate that neurons in ganglia on chronically decentralized hearts can generate spontaneous activity, a large fraction of which is correlated with cardiovascular or respiratory events.
Inhibition of cardiac vagal component of baroreflex by group III and IV afferents
Authors: McWilliam P. N. , Yang T.
Published: December 2017

The action of electrically evoked activity in somatic afferent fibers on the sensitivity of the baroreceptor reflex was examined in decerebrate cats. The sensitivity of the reflex was expressed as the difference between the maximum prolongation of R-R interval in response to carotid sinus pressure elevation and the mean of 10 R-R intervals immediately before pressure elevation. The control value of R-R interval prolongation was 192 +/- 50 ms. Stimulation (10 Hz) of group I and II fibers of the right peroneal nerve (evoked volleys recorded from the sciatic nerve) had no effect on R-R interval prolongation (171 +/- 45 ms). Recruitment of group III fibers (10 Hz) conducting at 23.6 +/- 0.65 m/s reduced the prolongation of R-R interval to 52 +/- 14 ms. Recruitment of group IV fibers (10 Hz) conducting less than 2.5 m/s further reduced the prolongation of R-R interval to 1.0 +/- 8.0 ms. It is concluded that the inhibition of the cardiac vagal component of the baroreceptor reflex produced by electrical stimulation of the peroneal nerve is mediated by afferent fibers of groups III and IV.
Effects of charged amphiphiles on cardiac cell contractility are mediated via effects on Ca2+ current
Authors: Post J. A. , Ji S. , Leonards K. S. , Langer G. A.
Published: December 2017

Exposure of isolated adult rabbit myocytes to the negatively charged amphiphile dodecylsulfate (DDS; 10 microM) increased the contraction amplitude to 185% of control. The positively charged amphiphile dodecyltrimethylammonium (DDTMA; 10 microM) decreased the amplitude to 58%. DDS increased Ca2+ uptake by the same cells, but this uptake was partially prevented by nifedipine. DDTMA had no effect on Ca2+ uptake. Ca2+ binding to isolated sarcolemma of neonatal heart cells was increased by 10 microM DDS and, at higher concentrations, reduced by DDTMA. Single-cell voltage-clamp studies, using isolated rabbit myocytes, showed that DDS enhanced L-type Ca2+ currents (ICa,L), whereas DDTMA depressed ICa,L. DDS shifted current-voltage (I-V) and isochronal inactivation curves of ICa,L in the negative direction, whereas DDTMA shifted them in positive direction. Furthermore, DDS depressed T-type Ca2+ currents (ICa,T), and DDTMA enhanced ICa,T. The inotropic effects of the amphiphiles are therefore mediated to a significant degree by ICa,L. The shifts in the I-V and inactivation curves of ICa,L and the effect on ICa,T can be explained by changes in the actual membrane potential (Em), induced by the insertion of the amphiphiles in the outer monolayer of the sarcolemma. However, the changes in the Em do not explain the effect on the maximal current, indicating effects on the channel per se, possibly by an alteration of the lipid environment.
Effect of adrenalectomy or sympathectomy on spinal cord blood flow in hypothermic rats
Authors: Iwai A. , Monafo W. W. , Eliasson S. G.
Published: December 2017

We used [14C]butanol distribution to measure regional spinal cord blood flow (RSCBF) in three groups of pentobarbital-anesthetized rats: 1) normals (n = 16); 2) after bilateral adrenalectomy (n = 18); and 3) after excision of the abdominal sympathetic chains (n = 12). Half of the rats in each group were maintained near normothermia; the remainder were colled to a rectal temperature of 25-27 degrees C. In intact rats, there was a 24-37% increase in RSCBF during hypothermia in the cord region C3-L6 inclusive. Neither operative procedure altered RSCBF during normothermia. In hypothermic adrenalectomized rats, RSCBF was elevated only in the C3-C5 cord segment. After sympathectomy, RSCBF was unchanged during hypothermia. In the cauda equina, flow fell in all hypothermic rats. The hypothermia-associated increases in RSCBF were not related to changes in mean arterial blood pressure. We conclude that adrenalectomy near-totally ablates the hypothermia-associated increase in RSCBF measured in intact rats and that abdominal sympathectomy totally ablates it. This evidence complements morphological evidence for adrenergic innervation of the spinal cord vasculature.
Stimulation of arterial 42K efflux by ATP depletion and cromakalim is antagonized by glyburide
Authors: Post J. M. , Jones A. W.
Published: December 2017

It has been suggested that cromakalim (BRL 34915)-induced vasorelaxation was associated with stimulation of ATP-sensitive K channels. The hyperpolarization resulting from activation of this mechanism might then inhibit voltage-dependent Ca2+ entry and subsequent contraction. The present study evaluated the similarities of 42K efflux stimulated by ATP depletion (verified by high-performance liquid chromatography) and by exposure to cromakalim (10 microM) in rabbit superior mesenteric arteries. Both depletion of intracellular ATP and exposure to cromakalim significantly stimulated 42K efflux (P less than 0.05). Glyburide (a selective inhibitor of ATP-sensitive K channels in pancreatic beta-cells) inhibited 42K efflux stimulated by ATP depletion and by cromakalim exposure. Glyburide (10 microM) had no significant effect on either basal 42K or the 42K efflux stimulated by norepinephrine and by K depolarization, which cause voltage and Ca2(+)-dependent activation of K channels. Glyburide therefore had a relatively selective effect on vascular smooth muscle. The glyburide-sensitive 42K efflux during ATP depletion and exposure to cromakalim was greatest in Ca2(+)-free solution (Mg raised to 10 mM). We conclude that in vascular smooth muscle both depletion of ATP and exposure to cromakalim stimulate 42K efflux via a glyburide-sensitive mechanism with properties similar to those of ATP-sensitive K channels observed in cardiac and pancreatic beta-cells.
A cardiodepressant factor isolated from blood blocks Ca2+ current in cardiomyocytes
Authors: Hallstrom S. , Koidl B. , Muller U. , Werdan K. , Schlag G.
Published: December 2017

A cardiodepressant factor (CDF) was isolated (salt free) from the plasma of dogs after hypovolemic-traumatic shock by column chromatography. CDF was found to exert a concentration-dependent negative inotropic effect in guinea pig papillary muscle; it reduced the amplitude of cell wall motion, the contraction and relaxation velocity, and the frequency of spontaneously beating rat cardiomyocytes in culture, effects that were rapidly reversible upon washout. By means of electrophysiological methods (whole cell recording with patch electrodes and voltage clamp) we tested the effect of CDF on adult guinea pig cardiomyocytes: application of CDF initially decreased the plateau by 7 mV (150 ms after peak of action potential) and reduced the action potential duration by 93 ms (76% of control action potential duration) at 50% and 88 ms (79%) at 90% of repolarization. The plateau was further reduced by 13 mV and the action potential duration was prolonged by 25 ms (106%) at 50% and was prolonged drastically by 156 ms (137%) at 90% of repolarization compared with control. Voltage-clamp experiments have shown that the most prominent effect of CDF is a strong reduction of ICa accompanied by inhibition of IK and subsequent repolarization. Similar results have been obtained with neonatal rat cardiomyocytes. Blockage of the calcium inward current can explain the negative inotropic and chronotropic effect of CDF in cardiomyocytes.
Quantitative analysis of blood vessel permeability of squirrel monkeys
Authors: Tompkins R. G.
Published: December 2017

A mathematical transport model was derived to analyze in vivo low-density lipoprotein (LDL) transport across the aorta, peripheral muscular arteries, and major veins of squirrel monkeys (primates that develop diet-induced atherosclerosis similar to humans). Parameters determining the relative magnitudes of intimal permeability and diffusion within the vascular wall were optimized by nonlinear regression methods. Transmural LDL concentrations demonstrating discrete spatial resolution along the endothelial surface were previously obtained after 30 min of tracer circulation using quantitative autoradiography. In this study, intimal mass transfer coefficient (k1) was determined in 87 vascular regions representing 280 transmural profiles. As a result of this analysis, the value of k1 was 1.7 +/- 0.4 x 10(-9) cm/s for arteries, 2.9 +/- 0.3 x 10(-9) cm/s for veins, and 60 +/- 120 x 10(-9) cm/s for enhanced LDL uptake regions, which was a significant increase (P less than 0.01). The effective diffusion coefficient was 6.2 +/- 3.7 x 10(-10) cm2/s for all vascular regions examined. As a result of this analysis, focal regions of enhanced LDL uptake were explained solely on the basis of intimal permeability.
Regional deformation and contractile function in canine right ventricular free wall
Authors: Chuong C. J. , Sacks M. S. , Templeton G. , Schwiep F. , Johnson R. L.
Published: December 2017

We used biplane cinefluorgraphy to study the regional deformation and local contractile function of the canine right ventricular free wall (RVFW) among the inflow, midventricular, and outflow regions. For a region delimited by three neighboring markers, under the assumption of homogeneous deformation, we identified the magnitudes and directions of principal shortening or elongation and changes in area every 16.7 ms. Furthermore, we extended this approach to study the alterations of these parameters during RV afterload increase by applying pulmonary artery (PA) occlusion. Results show that, at both control and PA occlusion states, the outflow region was subjected to maximal fractional area reduction (AR) and maximal time rate of fractional area reduction (ARR) during systole, with no differences between inflow and midventricular regions (P less than 0.05). At the control state, the percent AR and the corresponding value for ARR were 27% and 179%/s at the outflow, 19% and 112%/s at the midventricular, and 15% and 107%/s at the inflow region, respectively. During PA occlusion, they became 21% and 115%/s at the outflow, 14% and 97%/s at the midventricular, and 15% and 102%/s at the inflow region, respectively. Statistically, only the outflow region deformation was affected by PA occlusion (P less than 0.05). For the control state, we also compared the direction of regional principal shortening at end systole to the local transmural myocardial fiber orientations. The directions were found to correspond closely to the mean of all local transmural fiber orientations. This suggests that the regional RVFW deformation we measured is the combined deformation behavior from all the local participating myofibers.
Delayed-rectifier potassium channel activity in isolated membrane patches of guinea pig ventricular myocytes
Authors: Walsh K. B. , Arena J. P. , Kwok W. M. , Freeman L. , Kass R. S.
Published: December 2017

When the patch-clamp technique was used, a slowly activating, time-dependent outward current was identified in both cell-attached and excised membrane patches obtained from guinea pig ventricular myocytes. This macroscopic patch current was present in approximately 50% of patches studied and could be observed both in the presence and absence of unitary single channel activity (i.e., ATP-sensitive K+ channels). The time course of activation of the patch current resembled that of the whole cell delayed-rectifier K+ current (IK) recorded under similar ionic conditions, and the patch current and IK were activated over a similar membrane potential range. The time-dependent patch current could be eliminated when the Nernst potential for K+ equaled that of the pulse voltage. The patch current was inhibited by external addition of the tertiary ammonium compound LY 97241 (50 microM) and was augmented after internal application of the catalytic subunit of adenosine 3',5'-cyclic monophosphate-dependent protein kinase (500 nM). Deactivating tail currents with kinetics similar to those of IK could be recorded to cell-attached and excised patches. Unitary single channel events underlying the time-dependent patch current could not be resolved despite various attempts to increase single channel conductance. Thus our results suggest that a major component of delayed rectification in guinea pig ventricular cells is due to the activity of a high-density, extremely low conductance K+ channel.
Atrial ectopic pacemaker escape mediated by phasic vagal nerve activity
Authors: Rozanski G. J.
Published: December 2017

Effects of vagal nerve activity on atrial ectopic pacemaker foci were studied in vitro in strips of rabbit tricuspid valve. Transmembrane potentials were recorded from pacemaker and working atrial fibers superfused with Tyrode solution containing propranolol. Tissues were paced from the atrial muscle end at cycle lengths of 90, 70, or 50% of the intrinsic pacemaker cycle, and postganglionic vagal nerve endings were stimulated with brief trains of pulses (200 Hz; 100-200 microseconds) through a second electrode near the pacemaker. Vagal trains scanning diastole hyperpolarized pacemaker and surrounding fibers to a maximum membrane potential of -74.7 +/- 1.8 mV (normal maximum diastolic potential = -75.5 +/- 1.6 mV) and elicited a period of inexcitability lasting 217.9 +/- 27.3 ms (drive cycle = 90% of pacemaker cycle). Inexcitability was evident at critical diastolic intervals where vagal input prevented atrial impulses from activating the pacemaker allowing spontaneous discharges to occur, i.e., escape, late in diastole. Besides inexcitability, incidence and timing of escape impulses were determined by cumulative effects of drive cycle length, vagal stimulus, and subthreshold electrotonic input on intrinsic pacemaker cycle. These data suggest that phasic vagal stimuli may transiently protect atrial ectopic pacemaker foci from conducted sinus impulses by rendering pacemaker and surrounding fibers inexcitable. In the setting of a long sinus (drive) cycle length, phasic vagal activity may result in spontaneous discharges manifest as late atrial premature beats.
Dissociation between endothelium-dependent relaxations and increases in cGMP in systemic veins
Authors: Vidal M. , Vanhoutte P. M. , Miller V. M.
Published: December 2017

In canine systemic veins, in contrast to what is observed in mammalian systemic arteries, endothelium-dependent relaxations to the calcium ionophore A23187 are not diminished by the inhibitor of soluble guanylate cyclase, methylene blue. Therefore, experiments were designed to determine whether these relaxations in the veins are associated with the accumulation of guanosine 3',5'-cyclic monophosphate (cGMP). Rings of canine femoral arteries and veins with and without endothelium were suspended for the measurement of isometric force in organ chambers; cGMP was measured by radioimmunoassay. In arteries and veins contracted with norepinephrine, the tissue content of cGMP was greater in rings with than without endothelium. This difference was decreased by methylene blue (10(-5) M). A23187 (3 X 10(-7) M, for 1 min) increased the accumulation of cGMP, which was temporally related with the onset of relaxation in tissues with endothelium. Methylene blue inhibited the accumulation of cGMP in both blood vessels but inhibited the relaxations only in the arteries. In rings without endothelium, sodium nitroprusside (3 X 10(-7) and 10(-5) M) initiated increases in cGMP, which followed the onset of relaxation. Neither response to sodium nitroprusside was reduced by methylene blue. These results suggest that in canine femoral arteries and veins, relaxation of the smooth muscle to sodium nitroprusside are mediated by a mechanism distinct from changes in cGMP. Likewise, in canine systemic veins, endothelium-derived factor(s) released in response to A23187 also can initiate relaxation of the smooth muscle by a mechanism distinct from changes in cGMP.
Platelet interaction with vascular smooth muscle in synthesis of prostacyclin
Authors: Hechtman D. H. , Kroll M. H. , Gimbrone M. A. , Schafer A. I.
Published: December 2017

Because vascular smooth muscle cells (SMC) can be exposed to platelets at sites of significant arterial injury, we studied whether cultured rat aorta SMC can utilize platelet-derived arachidonate and prostaglandin (PG) endoperoxides (PGG2/PGH2) in the synthesis of prostacyclin (PGI2). SMC converted exogenous PGH2 to PGI2, measured by radioimmunoassay (RIA) of 6-keto-PGF1 alpha, despite cyclooxygenase inhibition or PGH2-receptor blockade. SMC produced increasing amounts of PGI2 in the presence of an increasing number of platelets when the two cell types were coincubated with arachidonate. Furthermore, aspirin-pretreated SMC produced PGI2 in response to arachidonate, ionophore A23187, or thrombin in the presence of platelets but not in their absence. SMC, by themselves unresponsive to thrombin, produced PGI2 during coincubation with thrombin-stimulated aspirin-pretreated platelets. Separation of the SMC monolayer and platelets with a filter did not prevent platelet-dependent PGI2 formation by the SMC. Finally, aspirin-pretreated SMC, in cosuspension with platelets, inhibited platelet aggregation in association with PGI2 production. These data indicate that 1) SMC can synthesize PGI2 from exogenously added PGH2 and from platelet-derived arachidonate or endoperoxides, 2) direct cell-cell contact is not required for intercellular endoperoxide transfer, and 3) SMC can inhibit platelet aggregation possibly through PGI2 production from platelet-derived endoperoxides.
Trabecular smooth muscle modulates the capacitor function of the penis. Studies on a rabbit model
Authors: Saenz de Tejada I. , Moroukian P. , Tessier J. , Kim J. J. , Goldstein I. , Frohrib D.
Published: December 2017

We investigated the role of trabecular smooth muscle tone in regulation of intracavernosal pressure, venous outflow resistance, and penile capacitance. In an isolated rabbit whole penis model, corpora cavernosa were infused with either contracting (high K(+)-norepinephrine combination) or relaxing (no added Ca(2+)-papaverine combination) physiological salt solutions while intracavernosal pressure was recorded. An infusion pump regulated by an intracavernosal pressure feedback mechanism enabled the measurement of flow necessary to maintain intracavernosal pressures at 30, 60, 90, 120, and 150 mmHg under steady-state conditions (inflow = outflow). These experiments allowed resistance to outflow from corpora to be calculated when trabecular smooth muscle was either constricted or relaxed. Decay in intracavernosal pressure over time from various predetermined intracavernosal pressures (150, 120, 90, 60, and 30 mmHg) was studied under conditions of zero inflow following contraction or relaxation of trabecular smooth muscle. This permitted calculation of the time constant, which together with the outflow resistance, permitted the calculation of penile capacitance. When smooth muscle is relaxed, venous outflow resistance is high, constant, and independent of intracavernosal pressure. Furthermore, relaxation of smooth muscle allows expansion of corpora with accumulation of volume under pressure, enabling the penis to act as a capacitor. This capacitor function is limited in the presence of constant high outflow resistance by stiffness of the fibroelastic elements of penis, tunica, and fibroelastic frame, which exhibit nonlinear deflection trends. Analysis of these variables has led us to propose a model for penile erection.
Unique strain history during ejection in canine left ventricle
Authors: Douglas A. S. , Rodriguez E. K. , O'Dell W. , Hunter W. C.
Published: December 2017

Understanding the relationship between structure and function in the heart requires a knowledge of the connection between the local behavior of the myocardium (e.g., shortening) and the pumping action of the left ventricle. We asked the question, how do changes in preload and afterload affect the relationship between local myocardial deformation and ventricular volume? To study this, a set of small radiopaque beads was implanted in approximately 1 cm3 of the isolated canine heart left ventricular free wall. Using biplane cineradiography, we tracked the motion of these markers through various cardiac cycles (controlling pre- and afterload) using the relative motion of six markers to quantify the local three dimensional Lagrangian strain. Two different reference states (used to define the strains) were considered. First, we used the configuration of the heart at end diastole for that particular cardiac cycle to define the individual strains (which gave the local “shortening fraction”) and the ejection fraction. Second, we used a single reference state for all cardiac cycles i.e., the end-diastolic state at maximum volume, to define absolute strains (which gave local fractional length) and the volume fraction. The individual strain versus ejection fraction trajectories were dependent on preload and afterload. For any one heart, however, each component of absolute strain was more tightly correlated to volume fraction. Around each linear regression, the individual measurements of absolute strain scattered with standard errors that averaged less than 7% of their range. Thus the canine hearts examined had a preferred kinematic (shape) history during ejection, different from the kinematics of filling and independent or pre-or afterload and of stroke volume.
Interleukin 6 stimulates growth of vascular smooth muscle cells in a PDGF-dependent manner
Authors: Ikeda U. , Ikeda M. , Oohara T. , Oguchi A. , Kamitani T. , Tsuruya Y. , Kano S.
Published: December 2017

We have investigated the effect of interleukin 6 (IL-6) on the growth of vascular smooth muscle cells (VSMC) isolated from rat aortas. Murine recombinant IL-6 significantly increased the number of VSMC and stimulated tritiated thymidine incorporation into VSMC in a dose-dependent manner. The IL-6-induced thymidine incorporation into VSMC was totally inhibited by the Ca2+ channel blocker verapamil; however, IL-6 showed no effects on the intracellular Ca2+ level ([Ca2+]i) in VSMC. Antibody against platelet-derived growth factor (PDGF) also totally inhibited the IL-6-induced thymidine uptake. PDGF caused a significant increase in the [Ca2+]i, which was totally inhibited by verapamil. IL-6 mRNA was not detected in unstimulated “quiescent” VSMC, but its expression was stimulated by exposure of VSMC to 10% fetal bovine serum. Immunohistochemical study using anti-PDGF antibody showed that IL-6 stimulated PDGF production in VSMC. These results support the premise that IL-6 is released by VSMC in an autocrine manner and promotes the growth of VSMC via induction of endogenous PDGF production.
Release of ANF, proANF 1-98, and proANF 31-67 from isolated rat atria by atrial distension
Authors: Dietz J. R. , Nazian S. J. , Vesely D. L.
Published: December 2017

The purpose of the present study was to determine if ANF and the NH2-terminus of the ANF prohormone are secreted simultaneously in response to atrial distension in isolated perfused rat atria. The experiments were conducted in paced left atria perfused with a modified Krebs buffer. Atrial pressure was increased from a baseline level of 2 mmHg to 8-9 mmHg for 60 minutes (distension) and then returned to 2 mmHg for 60 minutes in one group (n = 9) of isolated atria. In a second group of atria (n = 6), atrial pressure was maintained at approximately 2 mmHg throughout the experimental period. ANF secretion averaged 100 pg/min during the three 10-minute periods immediately preceding the increased atrial pressure and increased to 600-800 pg/min (P less than 0.001) when atrial pressure was raised. Secretion of the proANF 31-67 peptide increased from a value of approximately 100 pg/min immediately prior to distension to a peak of over 200 pg/min during distension (P less than 0.01). Secretion of proANF 1-98 increased from an average of 1.25 ng/min during the three periods immediately prior to distension to a peak of 2.5 ng/min during distension (P less than 0.01). These data indicate that ANF and the NH2-terminus of the ANF prohormone appear to be simultaneously secreted by isolated paced atria.
Fluid dynamics and the thromboembolic reaction in mesenteric arterioles and venules
Authors: Oude Egbrink M. G. , Tangelder G. J. , Slaaf D. W. , Reneman R. S.
Published: December 2017

In the mesentery of the anesthetized rabbit, the thromboembolic reaction after wall puncture lasts six times longer in arterioles than in venules, a difference that cannot be explained by fluid dynamic conditions before puncture. In the present study, it was investigated whether this difference in response between arterioles and venules results from a different degree of stenosis by the thrombus and/or a difference in velocity changes resulting in a different pressure drop over the thrombus. Arteriolar and venular mean red blood cell velocity and vessel diameter were measured before puncture and after this injury in the stenosed vessel segment and upstream. Thrombi with similar heights were formed in arterioles and venules and induced similar degrees of stenosis. A surface area reduction less than 55% induced only a small and similar decrease in volume flow (less than 10%) in arterioles and venules. Reduced velocity, a measure of wall shear rate, increased similarly in both vessel types for similar degrees of stenosis. In conclusion, changes in fluid dynamic factors, as induced by thrombus formation, cannot be held responsible for the difference in thromboembolic reaction between arterioles and venules.
Chronic alcohol consumption enhances sepsis-induced cardiac dysfunction
Authors: McDonough K. H. , Henry J. J.
Published: December 2017

Chronic alcoholism causes a cardiac contractile dysfunction which, in rats, may occur after 6 mo to 1 yr of alcohol consumption. Sepsis, on a more acute basis, can also induce intrinsic cardiac dysfunction. We tested the hypothesis that 2 mo of chronic alcohol feeding, while not directly causing overt depression of the myocardium, might sensitize the heart to a known cardiac stress, i.e., sepsis. We proposed that sepsis, induced in an alcoholic animal, would cause a more severe myocardial depression than in a nonalcoholic rat. Thus rats were fed a liquid diet with 36% of the total calories as alcohol for 8-10 wk and were then anesthetized and received an injection of live Escherichia coli (approximately 10(10) E. coli) through a dorsal subcutaneous catheter followed by a second dose approximately 5 h later. The following day, hearts were removed and, using the isolated working heart preparation, intrinsic contractile performance was assessed by generating ventricular function curves. Four groups of animals were studied. Hearts from the nonalcoholic-nonseptic group and the alcoholic-nonseptic group showed identical cardiac work (cardiac output x peak systolic pressure at the highest preload was 6,113 +/- 324 and 5,955 +/- 406 ml.min-1.mmHg-1, respectively). Work in the nonalcoholic-septic and the alcoholic-septic groups was decreased by 30 and 50%, respectively (4,806 +/- 478 vs. 2,917 +/- 435 ml.min-1.mmHg-1 at the highest preload). Thus 2 mo chronic alcohol consumption caused no overt cardiac dysfunction by itself but did exacerbate the myocardial injury induced by sepsis.
Longitudinal effect of captopril on aortic and arteriolar development in normotensive rats
Authors: Wang D. H. , Prewitt R. L.
Published: December 2017

Normotensive rats were chronically given 100 mg.kg-1.day-1 of captopril in their drinking water beginning 1 day before uninephrectomy. Mean blood pressure was significantly decreased 4 (17%) and 8 (18%) wk later in treated rats vs. age-matched controls. When histological techniques were used, a marked reduction of medial-intimal area of the abdominal aorta was found in treated rats at 4 (24%) and 8 (15%) wk without significant change in internal diameter. Cremaster arteriolar dimensions were measured by intravital microscopy after topical application of 10(-3) M adenosine. Structural diameter reductions occurred in large arterioles starting at 4 wk in treated rats and in small arterioles at 8 wk. Despite a significant increase in wall-to-lumen ratio of some large and small arterioles in treated rats, the wall cross-sectional area of these vessels was significantly decreased by captopril. Measured by stereological techniques, small arteriolar density decreased 17% at 4 wk and 13% at 8 wk in treated rats. Although decreased blood pressure may contribute to smaller aortic cross-sectional wall area, the effect of captopril was probably the major cause for smaller arteriolar lumens, reduced arteriolar cross-sectional wall areas, and arteriolar rarefaction.
Rate of oxygen loss from arterioles is an order of magnitude higher than expected
Authors: Popel Aleksander S. , Pittman Roland N. , Ellsworth Mary L.
Published: December 2017

Pages H921–H924: Aleksander S. Popel, Roland N. Pittman, and Mary L. Ellsworth. “Rate of oxygen loss from arterioles is an order of magnitude higher than expected.“ Page H922: Table 1 should appear as the following:

(See PDF)
Postnatal changes in heart mitochondrial calcium and energy metabolism
Authors: Wolf W. J. , Rex K. A. , Geshi E. , Sordahl L. A.
Published: December 2017

The newborn mammalian heart has less functional capacity compared with the adult, yet newborn myocardial mitochondrial respiratory activity is the same or exceeds that of adult. This study was aimed at determining the temporal changes in newborn rabbit heart mitochondrial energy-linked Ca2+ transport during early postnatal development. At birth, substrate-supported Ca2+ uptake is twice that of adult and declines toward adult rates during the first 14 days. Both NADH- and succinate-linked respiration are equivalent to adult values at birth, increase transiently during the first 7 days, and then decline toward adult. Newborn heart mitochondrial preparations exhibit the same membrane potential (delta psi) values during Ca2+ uptake and have comparable rates of Na(+)-induced Ca2+ efflux as adult. Creatine kinase (CK) activity is very low in 1- to 7-day-old newborn mitochondria and increases rapidly toward adult values after 10 days of age. The decreasing rates of Ca2+ uptake do not appear to be related to respiratory activity, membrane potential, or increased cycling of Ca2+ but rather to a direct effect on the mitochondrial Ca2+ uniporter. Preliminary studies indicate changes in mitochondrial membrane phospholipids during early development that may be related to the increasing CK activity and decreasing Ca2+ uptake and respiration. We postulate that mitochondrial membrane lipid changes in early postnatal development may be the causative factor underlying these changes in functional activity.
Systolic and diastolic dysfunction of the left ventricle induced by dietary taurine deficiency in cats
Authors: Novotny M. J. , Hogan P. M. , Paley D. M. , Adams H. R.
Published: December 2017

Isovolumic left ventricular (LV) preparations were used to assess myocardial failure associated with dietary taurine deficiency in cats. Adult female cats (n = 12) were fed a purified diet devoid of taurine for 6-8 mo. Six of the cats received 1,000 mg of crystalline taurine orally once daily. The remaining six cats were not provided taurine replacement. Compared with control preparations, hearts isolated from taurine-deficient cats generated significantly lower values for developed LV systolic pressure (107 +/- 6 vs. 66 +/- 15 mmHg; P less than 0.05), maximal rate of LV pressure rise (+dP/dtmax; 1,103 +/- 38 vs. 718 +/- 172 mmHg/s; P less than 0.05), and fall (-dP/dtmax; 930 +/- 46 vs. 587 +/- 129 mmHg/s; P less than 0.05). LV function curves generated by hearts from taurine-deficient cats were shifted downward and to the right of control curves, demonstrating inotropic depression. In addition, end-diastolic pressure-volume (compliance) relationships in hearts from taurine-deficient cats were shifted downward and to the right of controls in the direction of increased chamber compliance or distensibility. Ten millimolar taurine significantly improved inotropic indexes only in hearts from taurine-deficient cats but failed to affect diastolic compliance. Myocardial contractile dysfunction and LV chamber dilatation in hearts from taurine-deficient cats verify a causal association between dietary deficiency of this amino acid and dilated cardiomyopathy in this species.
Tachycardia-induced cardiomyopathy: effects on blood flow and capillary structure
Authors: Spinale F. G. , Zellner J. L. , Tomita M. , Tempel G. E. , Crawford F. A. , Zile M. R.
Published: December 2017

Chronic supraventricular tachycardia (SVT) causes a dilated cardiomyopathy. A potential factor contributing to the development of SVT-induced cardiomyopathy is abnormal myocardial blood flow (MBF). The purpose of this study was to relate changes in left ventricular (LV) function, MBF, and capillary structure with the development of SVT-induced cardiomyopathy. LV function and MBF were measured in two groups of conscious pigs: sham control (CON; n = 8) and after 3 wk of atrial pacing (SVT; 240 beats/min; n = 8) using echocardiography-catheterization and microspheres. Measurements were made under three states: 1) at rest with a basal heart rate, 2) during rapid atrial pacing (240 beats/min), and 3) during adenosine infusion (1.5 microM.kg-1.min-1) without pacing. LV capillary density, diameter, wall thickness, and capillary-myocyte distance were measured in four additional pigs from each group. LV fractional shortening was lower, and left atrial pressure was significantly higher in the SVT group compared with CON at rest, during pacing, and with adenosine (P less than 0.05). In the CON group, average LV-MBF at rest was 2.0 +/- 0.2 ml.min-1.g-1, increased with pacing to 3.0 +/- 0.2 ml.min-1.g-1 (P less than 0.05), and increased further with adenosine to 4.1 +/- 0.3 ml.min-1.g-1 (P less than 0.05). In all states, SVT LV-MBF was significantly reduced vs. CON (P less than 0.05); SVT LV-MBF was 0.8 +/- 0.2 ml.min-1.g-1 at rest, increased to 1.3 +/- 0.3 ml.min-1.g-1 with rapid pacing (P less than 0.05), and remained unchanged during adenosine (1.3 +/- 0.4 ml.min-1.g-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of fasting and refeeding on the proliferative response of rat aorta to injury
Authors: Ridray S. , Capron L. , Heudes D. , Picon L. , Ktorza A.
Published: December 2017

To explore the interplay between the mitotic activity of arterial smooth muscle cells and the variations of plasma glucose and insulin concentrations, we have studied over 14 days the response of thoracic aorta to injury with a balloon catheter in rats submitted to fasting and refeeding. Animals were fasted from the day before until the third day after injury. The proliferative reaction of intima-media was assessed 2, 3.5, 4, 6, 8, and 14 days after injury, comparing freely fed with fasted-refed rats. Fasting decreased plasma glucose and insulin concentrations and DNA synthesis by intima-media, whereas refeeding increased these three variables transiently. The DNA content of intima-media at any time during the response to injury and the intimal thickening on day 14 were not influenced by the sequence of fasting and refeeding, which suggests that the early decrease in DNA synthesis induced by fasting had been compensated for by the later increase in DNA synthesis induced by refeeding. In conclusion, besides hormonal influences (such as insulin), metabolic influences (such as the availability of energetic fuels) are likely to act on the proliferative response of arteries to injury.
Left ventricular dysfunction induced by chronic alcohol ingestion in rats
Authors: Capasso J. M. , Li P. , Guideri G. , Anversa P.
Published: December 2017

To determine whether moderate ingestion of alcohol for protracted periods of time affects normal cardiac performance and produces myocyte damage, male Fischer 344 rats at 4 mo of age were given 30% ethanol in their drinking water every day for a period of 8 mo. Experimental animals and age-matched controls were examined hemodynamically and morphometrically at 12 mo of age. Body and cardiac growth were depressed in alcoholic animals by 15 and 12%, respectively. Although left ventricular (LV) weight was reduced by 14% in alcoholic rats, no difference in right ventricular (RV) weight was noted, and consequently the ratio of RV weight to body weight increased by 12%. Systemic arterial pressures as well as LV peak systolic pressure decreased in alcoholic rats despite an unchanged heart rate. Myocardial contractility in alcoholic rats was further depressed as revealed by a significant decrease in the peak rate of ventricular pressure decay. Importantly, end-diastolic pressure was elevated 5.2-fold in the left ventricle and 2.9-fold in the right ventricle after 8 mo of ethanol consumption. LV diastolic chamber volume increased through myocardial remodeling as the longitudinal axis and transverse diameters from the base to the apex increased in experimental animals while the thickness of the LV diminished. Structural and hemodynamic alterations resulted in a 571% increase in the volume of diastolic circumferential wall stress on the left ventricle. Damage to the myocardium was increased in alcoholic animals with the volume percent of myocardial lesions increasing 342% in the wall of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of increased free [Mg2+]i with myocardial stunning on sarcoplasmic reticulum Ca(2+)-ATPase activity
Authors: Krause S. M.
Published: December 2017

Intracellular free Mg2+ concentration [( Mg2+]i) has been shown to increase markedly during ischemia from 0.6 to 3.2 mM and remain elevated severalfold at 1.5 mM after reperfusion of the stunned heart. The significance of this rise in [Mg2+]i after reperfusion on cellular function is not well known. To determine whether this increase in free [Mg2+] would alter the function of the sarcoplasmic reticulum (SR), the effects of an increase in free [Mg2+] on the SR Ca(2+)-dependent Mg(2+)-adenosinetriphosphatase (ATPase) activity were examined in SR isolated from Langendorff-perfused, isovolumic rabbit hearts after 15 min of reversible ischemia (global stunning). Oxalate-supported Ca2+ transport, assessed under identical conditions (0.4 mM free Mg2+, 15 microM free Ca2+), was reduced from 495 +/- 29 to 395 +/- 27 nmol Ca2+.mg protein-1.min-1 in control and stunned hearts, respectively, indicating a defect in enzyme function. This defect was confirmed by a decrease in the maximal Ca(2+)-dependent Mg(2+)-ATPase activity. An increase in the free [Mg2+] to simulate conditions after reperfusion leads to a decrease in the Ca2+ sensitivity of the SR Mg(2+)-ATPase. Fifty percent activation was shifted from a control free [Ca2+] of 0.42 microM at 0.6 mM free [Mg2+] to 0.63 microM free [Ca2+] at 1.2 mM free [Mg2+], conditions that simulate the reperfused stunned myocardium. These results indicate that after stunning the observed decline in SR Ca2+ transport, determined under similar incubation conditions, may be further jeopardized by the sustained increase in free [Mg2+].(ABSTRACT TRUNCATED AT 250 WORDS)
Importance of freezing time when iodoantipyrine is used for measurement of cerebral blood flow
Authors: Williams J. L. , Shea M. , Furlan A. J. , Little J. R. , Jones S. C.
Published: December 2017

The goal of the present study was to determine effects of delay of freezing of the brain on distribution of [14C]iodoantipyrine in the brain. Blood flow to parietal cerebral cortex (CBF) and choroid plexus was measured with the indicator fractionation technique and quantitative autoradiography. After injection of iodoantipyrine, each rat was decapitated, and the head was immersed in chlorodifluoromethane (-40 degrees C). The brain was removed from the skull after it was frozen. In some rats, heads were immersed immediately after decapitation, and CBF was markedly heterogeneous. In another group, heads were frozen 3 min after decapitation. In this case, CBF was uniform in its distribution. Average CBF was similar in groups with immediate and delayed freezing (90-104 ml.min-1 x 100 g-1). In contrast, delays in freezing decreased blood flow to choroid plexus from 551 +/- 115 to 261 +/- 48 ml.min-1 x 100 g-1. Our findings indicate that immediate freezing of the brain after decapitation is necessary to prevent diffusion of iodoantipyrine from regions of high blood flow to regions of lower blood flow and underestimations of blood flow in regions with high blood flow.
Role of granulocytes and C5a in myocardial response to zymosan-activated serum
Authors: Stahl G. L. , Fletcher M. P. , Amsterdam E. A. , Longhurst J. C.
Published: December 2017

Although previous studies have demonstrated that complement (C)5a causes myocardial ischemia and mechanical dysfunction, the cardiac response of endogenously produced C5a and C5a des-Arg in zymosan-activated serum (ZAS) and the critical role of granulocytes in this process are poorly understood. Therefore, we compared the coronary and cardiac effects of ZAS and purified C5a and investigated the role of leukocyte adhesion-promoting receptors (i.e., CD11/CD18). Like purified C5a, ZAS (0.5 ml) significantly reduced coronary artery blood flow and regional segment shortening, whereas coronary venous granulocyte concentration and myocardial lactate extraction were significantly decreased. A monoclonal antibody (MoAb) to C5a/C5a des-Arg attenuated ZAS-induced cardiac alterations. Three minutes of continuous infusion of C5a or ZAS induced sustained decreases in coronary venous granulocyte concentrations, although coronary flow and segment shortening returned to control levels after 2 min. Another MoAb, IB4, directed against CD18, significantly inhibited ZAS-induced granulocyte extraction and associated cardiac effects. Thus, cardiac dysfunction occurs after activation of the complement cascade with zymosan resulting in extraction of granulocytes mediated by the CD18 adherence glycoprotein. Furthermore, intramyocardial retention of granulocytes appears necessary for the initial and full ZAS-induced cardiac dysfunction.