bluuebunny/crossref_metadata_2025 huggingface dataset:
Ontogeny of neonatal pulmonary vascular pressure-flow relationships
Authors: Tod M. L. , Yoshimura K. , Rubin L. J.
Published: December 2017

Previously we reported that pulmonary vascular pressure gradients determined by vascular occlusion varied as a function of neonatal age. The purpose of this study was to evaluate the effect of blood flow on pressure gradients during normoxia (inspired O2 28%) and hypoxia (inspired O2 4.2%) in isolated, indomethacin-treated lungs obtained from lambs at less than 1, 2-4, 12-14, and 30-32 days of age (n = 6 at each age). The total pulmonary pressure gradient was partitioned into pressure gradients across relatively indistensible arteries and veins and relatively compliant vessels in the middle region (delta Pm) by inflow and outflow occlusions at flows of 25, 50, 75, and 100 ml.kg-1.min-1. During normoxia, lungs from lambs less than 1 day of age had significantly greater pressures at each flow than lungs from older lambs, due primarily to a significantly greater delta Pm in this age group. During hypoxia, the greatest vasoconstriction occurred in the youngest group, also due mostly to an increased delta Pm. This enhanced response to hypoxia in the younger age groups was due to inhibition of prostaglandin synthesis; without indomethacin treatment, the older age groups had a greater hypoxic pressor response than the younger groups. The arterial vascular resistance at all ages was relatively constant as a function of blood flow during both normoxia and hypoxia, whereas the total and middle vascular resistances generally decreased as a function of flow. The venous resistance initially decreased and then was constant. These results suggest that the neonatal pulmonary circulation h as a fixed arterial resistance, a slightly distensible venous region at low flows, and a more distensible middle region.
Enalapril suppresses normal accumulation of elastin and collagen in cardiovascular tissues of growing rats
Authors: Keeley F. W. , Elmoselhi A. , Leenen F. H.
Published: December 2017

We have investigated the effect of enalapril, an angiotensin converting-enzyme (ACE) inhibitor, on the accumulation of ventricular and vascular collagen and elastin in young, growing rats. Beginning at either 4 or 10 wk of age, male Wistar rats were treated with enalapril for 2 or 5 wk. Enalapril treatment had no significant effect on body weight and small, generally non-significant effects on systolic and diastolic blood pressures. In contrast, young enalapril-treated animals showed a marked decrease in accumulation of total elastin and collagen in both large (aorta, renal, and carotid) and smaller (superior and large mesenteric) arteries, as well as a large reduction in total collagen in both left and right ventricles. This effect also was present but less pronounced in rats treated with enalapril beginning at 10 wk of age. These data indicate that inhibition of ACE activity during a period of rapid growth significantly reduces accumulation of vascular and ventricular connective tissue and suggests that angiotensin II may be important in normal cardiovascular development and growth.
Heterogeneity in geometrical alterations of main branches of left coronary artery induced by increase in ventricle volume
Authors: Gerova M. , Barta E. , Stolarik M. , Gero J.
Published: December 2017

With the use of ultrasound technique, segment length and diameter of ramus circumflexus (RC) and ramus interventricularis anterior (RIA) in the dog heart, placed in a bath, were monitored under constant pressure. When the left and/or right ventricular volume was increased by 150% of the normal diastolic filling, segment length of RC increased by 2.54 +/- 0.17 and 2.15 +/- 0.06%, respectively, and diameter of RC decreased by 4.72 +/- 0.20% and by 4.60 +/- 0.20%, respectively. The same filling of the left and/or right ventricle induced in the proximal third of RIA an increase in segment length by 11.40 +/- 0.55 and 12.2 +/- 0.42%, respectively, and a decrease in diameter by 9.41 +/- 0.42% and by 10.01 +/- 0.31%, respectively. The latter values of RIA were significantly higher (P less than 0.001) than those registered in RC. The deformations of RIA decreased toward the periphery of the vessel. By the fact that conduit coronary artery tracks instantaneously the increase of the volume of the left and right ventricle, its contribution to the total coronary resistance increases dynamically. With the ventricular volume increased by 150%, the RC contributes to the total coronary resistance by 14% and RIA in the proximal part contributes by 23%, with values significantly higher than control (10%) (Malindzak, G. S. In: The Coronary Artery. London: Croom Helm, 1982, p. 241-267). The results imply a methodical consequence, namely that the diameter of the respective coronary artery is an index of smooth muscle activity only if both perfusion pressure and volume of the heart are maintained constant.
Stem pressure at the origin of intracranial collateral vessels
Authors: Greene G. M. , Muhonen M. G. , Detwiler K. N. , Heistad D. D. , Loftus C. M.
Published: December 2017

The relationship between pressure at the functional site of origin of intracranial collateral channels (Pstem) and systemic pressure allows an estimation of the size of vascular channels from which collateral vessels originate. In this study, Pstem was determined in anesthetized dogs. A branch of the middle cerebral artery was perfused through a closed system with autologous blood. Tissues with regional cerebral blood flow (rCBF) less than or equal to 10 ml.100 g-1.min-1 (collateral-dependent zone) were identified using radioactive microspheres. Sequential injections of nonradioactive microspheres were made into the cannulated vessel to progressively occlude the terminal capillary bed. Injection of nonlabeled spheres was terminated when backpressure no longer increased, and the final rCBF measurement was made. There was a linear relationship between backpressure and flow to the collateral-dependent tissues. When rCBF within these tissues was zero, the corresponding value for backpressure (Pstem) was 79 +/- 4% (mean +/- SD) of mean arterial pressure. The high value for Pstem suggests that cerebral collateral channels arise in part from large vessels.
Regulation of adrenal medullary and cortical blood flow
Authors: Breslow M. J.
Published: December 2017

Before 1986, little was known concerning regulation of blood flow to adrenal medulla and cortex. With the introduction of a radiolabeled microsphere methodology, which permitted independent measurement of blood flow to the two regions, it became apparent that medulla and cortex regulate blood flow independently and that both regions receive levels of blood flow considerably in excess of that required for nutrient delivery. It is likely that abundant blood flow serves to speed entry of adrenal secretory products into the systemic circulation. Coupling of blood flow with secretion is particularly apparent in medulla, where severalfold increases in blood flow occur during catecholamine secretion elicited by hemorrhage, hypoxia, and splanchnic nerve stimulation. Both catecholamine secretion and medullary vasodilation are neurally mediated. The two responses can be pharmacologically dissociated, suggesting possible direct innervation of adrenal vessels. However, morphological confirmation of vascular innervation is not available, and effects of released chromaffin cell products on adjacent vessels are also possible. In contrast to medulla, cortical secretory activity is not associated with altered blood flow. However, neural elements are found in close proximity to cortical vessels, and the cortical vasculature responds to changes in O2 tension and to a number of pharmacological agents. In addition, several studies indicate that cortical secretory activity can be modulated by changes in blood flow. The response of both vasculatures to pharmacological agents is, in many instances, different from responses observed in other vascular beds. These data indicate that the adrenal has evolved unique vasoregulatory mechanisms, either because vasoactive compounds are present in such high concentration, or because blood flow plays an important role in the secretory process.
Rapid resetting of baroreflexes in hypertensive dogs
Authors: Brunner M. J. , Kligman M. D.
Published: December 2017

The hypothesis tested was that the rapid resetting of the arterial baroreflex control of arterial pressure in normotension could be demonstrated in experimental hypertension. After the development of experimental hypertension (using a bilateral renal wrap technique), rapid resetting of arterial pressure and heart rate (HR) was acutely assessed under pentobarbital sodium anesthesia in hypertensive and normotensive vagotomized dogs. The carotid sinus area was isolated and perfused at controlled carotid sinus pressures (CSPs). Baroreflex response [mean arterial pressure (MAP) and HR] curves were measured after three carotid sinus conditioning pressures (50, 125, and 200 mmHg) were applied. For the MAP response, the CSPo (CSP at point of maximum reflex gain) increased significantly to the same extent in both groups with increasing conditioning pressures (with 22.2 and 16.7% resetting in the normotensive group, and 20.3 and 14.2% resetting in the hypertensive group). We conclude that short-term adjustments to changes in prevailing pressure (rapid resetting) occur in the arterial pressure response in experimental hypertension to the same extent seen in normotension.
Differences and similarities in albumin and red blood cell flows through cerebral microvessels
Authors: Tajima A. , Nakata H. , Lin S. Z. , Acuff V. , Fenstermacher J.
Published: December 2017

The hypothesis that microvessels in brain parenchyma are continuously perfused by plasma but intermittently perfused by red blood cells (RBCs) was tested in awake Sprague-Dawley rats. The microvascular distribution volumes of radioiodinated serum albumin (RISA) and 51Cr- and 55Fe-labeled RBCs were measured for periods from 15 s to 30 min. Local cerebral blood flow (LCBF) was assessed by the iodoantipyrine technique. The RISA and RBC distribution volumes were constant in the 12 areas studied from 15 s onward. These data fit a model of continuous plasma flow with intermittent RBC flow (and thus support the hypothesis), but they are also consistent with other models, e.g., continuous flow of both plasma and RBCs through all perfused microvessels. In parallel with LCBF, microvascular blood volume varied greater than 10-fold among brain areas. Relative to arterial hematocrit, microvascular hematocrits were low, which indicates that the passage of RBCs through parenchymal microvessels is more rapid than that of RISA. This could be the result of both the Fahraeus effect and intermittent RBC flow.
Transforming growth factor-beta 1 inhibits L-arginine-derived relaxing factor(s) from smooth muscle cells
Authors: Junquero D. C. , Schini V. B. , Scott-Burden T. , Vanhoutte P. M.
Published: December 2017

The effects of human recombinant interleukin-1 beta were investigated on the release of nonprostanoid relaxing substances from cultured aortic smooth muscle cells from Wistar rats. Cells cultured on microcarrier beads were packed in columns. The perfusate over these beads was bioassayed by measuring changes in isometric tension of contracted arteries without endothelium. The perfusates from interleukin-1 beta-treated smooth muscle cells, but not from control cells, evoked relaxations. The relaxations persisted when the transit time between the cultured smooth muscle cells and the detector was increased to 5 min. The effect of relaxing substance(s) was inhibited by cycloheximide, nitro-L-arginine, methylene blue, and transforming growth factor-beta 1. L-Arginine but not D-arginine overcame the blockade by nitro-L-arginine. Superoxide dismutase potentiated the relaxations. In cells cultured in multiwell plates, interleukin-1 beta evoked a time- and concentration-dependent accumulation of nitrite in the extracellular medium that was inhibited dose dependently by transforming growth factor-beta 1. These studies demonstrate that cultured smooth muscle cells can be stimulated to produce nitric oxide-related substances and that the inducible pathway is modulated by transforming growth factor-beta 1.
Endotoxin impairs flow-induced vasodilation of porcine coronary arterioles
Authors: Kuo L. , Chilian W. M. , Davis M. J. , Laughlin M. H.
Published: December 2017

The purpose of this study was to test the hypothesis that endotoxemia impairs endothelium-dependent (both receptor-mediated and flow-induced) vasodilation in porcine coronary arterioles. Coronary arterioles were isolated from three groups of 4- to 8-wk old (10.3 +/- 0.8 kg) pigs: endotoxemic (E; 250 micrograms/kg endotoxin iv), control (C; equal volume of saline), and untreated pigs (UT). Subepicardial arterioles (60-120 microns) were isolated and cannulated with two micropipettes that were connected to two independent reservoir systems. Intraluminal pressure was set at 60 cmH2O throughout the experiments. All C vessels developed spontaneous tone and exhibited flow-induced vasodilation from 65 to 95% maximal diameter. Spontaneous tone developed in only three of five arterioles from E pigs, and flow-induced vasodilation was not observed in any arteriole from E pigs. Spontaneous tone developed in all six arterioles isolated from UT pigs but disappeared in four of these vessels as a result of 1 h of in vitro incubation with endotoxin (2.5 micrograms/ml). Flow-induced vasodilation was also abolished in these vessels after 1 h of endotoxin exposure. Incubation with 3 mM L-arginine, in vitro, restored flow-induced vasodilation in E arterioles and endotoxin-treated UT arterioles. Vasoconstriction induced by acetylcholine (ACh) and vasodilation induced by nitroprusside (NP) and bradykinin (BK) were similar in arterioles from all groups. In contrast, endotoxin impairs flow-induced vasodilation of coronary arterioles. The mechanism responsible for the impairment of flow-induced vasodilation seems to reside in disruption of the L-arginine/nitric oxide pathway.
Hemodynamic and proteolytic effects of intravenous injection of purified human plasma kallikrein
Authors: Naess F. , Roeise O. , Johansen H. T. , Stadaas J. O. , Aasen A. O.
Published: December 2017

To investigate the precise hemodynamic effects of purified human plasma kallikrein, small doses (0.3 U/kg) of this proteolytic enzyme were infused over 10 s in five pigs. Hemodynamic performance was evaluated by means of a Swan-Ganz catheter, and parameters of the plasma kallikrein-kinin, coagulation, and fibrinolytic systems were determined by means of chromogenic peptide substrate assays. The infusions of plasma kallikrein were followed by rapid decreases in mean arterial pressure (to 43 +/- 2% of baseline values) and increases in cardiac output (to 145 +/- 6% of baseline values), accounting for marked decreases in systemic vascular resistance, to 28 +/- 1% of initial values. Heart rate, mean pulmonary arterial, central venous, and pulmonary capillary wedge pressures did not change after the injection. Pulmonary vascular resistance decreased to 69 +/- 3% of baseline values. The hemodynamic changes gradually normalized during the following 10 min. Functional levels of prekallikrein, kallikrein, kallikrein inhibition, prothrombin, antithrombin III, plasmin, and antiplasmin were not affected by the injection or the resulting hemodynamic changes; the hematocrit and the number of circulating leukocytes or platelets were also unaffected.
Characteristics of calcium currents in rabbit portal vein myocytes
Authors: Cox R. H. , Katzka D. , Morad M.
Published: December 2017

The properties of voltage-dependent Ca2+ channels were studied in isolated portal vein myocytes using the whole cell voltage-clamp method. Ca2+ currents (ICa) were identified based on their activation and inactivation potential, their dependence on external Ca2+ ([Ca2+]o), their suppression by organic or inorganic Ca2+ channel blockers, their augmentation by BAY K 8644, and their insensitivity to tetrodotoxin or alterations in external Na+ ([Na+]o). Changing the holding potential from -90 to -40 mV decreased ICa from 4.6 +/- 0.6 to 2.0 +/- 0.3 pA/pF at 0 mV but did not shift its voltage dependence significantly. The voltage dependence of steady-state inactivation and activation was represented by Boltzmann distributions with the following parameters: inactivation, half-maximal voltage (V0.5) = -32 +/- 7 mV and slope factor (k) = 6.1 +/- 0.2 mV; activation, V0.5 = -15 +/- 4 mV and k = 5.6 +/- 0.6 mV. Doubling the [Ca2+]o increased ICa and shifted the voltage dependence of its activation and inactivation by approximately 10 mV toward more positive potentials without altering the window currents. Substituting Na+, Ba2+, or Sr2+ for Ca2+ as the charge carrier through the Ca2+ channel slowed the rate of its inactivation and shifted its voltage dependence toward more negative potentials. Divalent selectivity of the Ca2+ channel showed an apparent concentration dependence: at 2 mMISr less than IBa = ICa, while at 10 mM ICa less than ISr = IBa. Because 50-100 microM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid abolished the apparent concentration dependence of the divalent ion selectivity, this phenomenon was attributed to a high Ca2+ selectivity of the channel. Our data support the presence of only one type of Ca2+ channel in rabbit portal vein myocytes with characteristics similar to the L-type Ca2+ channel described in other cells, but with somewhat different divalent selectivity, holding potential, and [Na+]o dependence.
Platelet cGMP, but not cAMP, inhibits thrombin-induced platelet adhesion to pulmonary vascular endothelium
Authors: Venturini C. M. , Weston L. K. , Kaplan J. E.
Published: December 2017

We have compared the effects of intracellular pathways initiated by nitric oxide and prostacyclin on thrombin-induced platelet adhesion to endothelial cells. Platelet aggregate adhesion was enhanced when endothelial monolayers were pretreated with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide production. In addition, decreased platelet aggregate adhesion was seen when platelets were pretreated with 8-bromoadenosine 3',5'-cyclic monophosphate (8-bromo-cAMP) or 8-bromoguanosine 3',5'-cyclic monophosphate (8-bromo-cGMP). Single platelet adhesion in isolated perfused lungs under flow conditions in the presence of shear was also assessed. Pretreatment of platelets with either Iloprost, in a dose sufficient to decrease platelet aggregation, or 8-bromo-cAMP did not affect platelet adhesion. However, pretreatment of platelets with 8-bromo-cGMP significantly reduced single platelet adhesion to endothelium. These studies illustrate that nitric oxide inhibits platelet adhesion to endothelium in the presence of shear. They further indicate that prostacyclin is also a regulator of this response but has effects more specifically related to the inhibition of platelet aggregation than platelet-endothelium interactions.
Cellular mechanisms involved in the vascular myogenic response
Authors: Meininger G. A. , Davis M. J.
Published: December 2017

By definition, the myogenic response is the contraction of a blood vessel that occurs when intravascular pressure is elevated and, conversely, the vasodilation that follows a reduction in pressure. Over the last several decades numerous investigators have demonstrated the importance of the myogenic response in the local regulations of blood flow, capillary pressure, and in the generation of basal vascular tone. Despite the considerable information obtained from these investigations, information about the cellular mechanisms that underlie this response has been slow to accumulate. Because of the physiological significance of the myogenic response, its mechanistic basis represents an important subject for research. Currently, there are several broad hypotheses concerning the sequence of events that couple changes in intravascular pressure or stretch with alterations in vascular smooth muscle activation. These hypotheses include 1) altered membrane properties leading to activation of ion channels; 2) modulation of biochemical cell-signaling pathways within vascular smooth muscle; 3) length-dependent changes in contractile protein function; and 4) endothelial-dependent modulation of vascular smooth muscle tone. This review summarizes current work relative to each of these hypotheses and describes a possible sequence of events to account for myogenic activation of vascular smooth muscle.
Chronic coronary arterial stenosis impairs alpha 1-adrenoreceptor signaling and cardiac performance in rats
Authors: Meggs L. G. , Huang H. , Li P. , Capasso J. M. , Anversa P.
Published: December 2017

Coronary stenosis was induced in rats to determine whether chronic coronary artery constriction resulted in impairment of cardiac pump performance, alterations in alpha 1-adrenoreceptor signal transduction, and inadequate myocardial hypertrophy, and these parameters were examined 6 mo later. A 50% reduction in coronary diameter was associated with an elevation in left ventricular end-diastolic pressure, whereas left ventricular peak systolic pressure, rate of pressure rise and decay were reduced. The hypertrophic response was modest, since statistically significant increases of 11% and 23% in left and right ventricular weights were measured. Radioligand binding documented an 18% and a 38% statistically significant reduction in alpha 1-adrenoreceptor density of the left and right myocardium, respectively. ADP ribosylation of the 41-kDa substrate by pertussis toxin showed a 16% significant decrease of this parameter in the left myocardium. Moreover, a 29% decrease in norepinephrine stimulated phosphoinositol turnover was seen in myocytes, and this change was statistically significant. The depressed generation of intracellular second messengers linked to the alpha 1-adrenoreceptors was found in conjunction with a 19% significant reduction in myocardial norepinephrine content. In conclusion, the long-term effects of coronary stenosis involve impaired transduction of adrenergic signals, which, in combination with constraints on myocardial growth, may participate in the onset of ventricular dysfunction in this model.
L-selectin function is required for beta 2-integrin-mediated neutrophil adhesion at physiological shear rates in vivo
Authors: Von Andrian U. H. , Hansell P. , Chambers J. D. , Berger E. M. , Torres Filho I. , Butcher E. C. , Arfors K. E.
Published: December 2017

In vivo interactions between neutrophils and endothelial cells (EC) follow a multistep process involving two distinct neutrophil adhesion receptors. L-selectin, constitutively functional on resting neutrophils, mediates an activation-independent primary interaction resulting in rolling along the venular wall. Subsequent activation of rolling neutrophils induces upregulation and functional activation of beta 2-integrins (CD11/CD18) leading to firm attachment. Based on previous findings we hypothesized that, under shear force, rolling may be essential for successful neutrophil-EC recognition. Here we report results of our studies of human neutrophil behavior in interleukin (IL)-1-activated rabbit mesentery venules, an interaction that requires both L-selectin and beta 2-integrins. Rolling of human neutrophils is L-selection mediated; it was strongly reduced by monoclonal antibody inhibition or enzymatic removal of L-selectin. Furthermore, activation induced L-selectin shedding and, in a dose- and time-dependent fashion, rendered neutrophils unable to recognize inflamed EC despite expression of active beta 2-integrins, which promoted adhesion in vitro. Neutrophils activated for 5 min or longer lost most of their ability to roll. However, 1-3 min after activation, rolling was reduced (not abolished), and cells that were still able to roll displayed a significant tendency for a CD18-dependent transition from rolling to sticking. The whole sequence of events, rolling, sticking, and transendothelial migration, could be observed if an extravascular chemotactic stimulus was applied by superfusing mesenteries with leukotriene B4. Under such conditions, sticking and emigration was blocked when rolling was inhibited by enzymatic removal of L-selectin. Our results indicate that primary neutrophil interaction with inflamed EC through the L-selectin is a prerequisite for neutrophil function at physiological shear rates in vivo.
Age-dependent changes in alpha-adrenoceptor-mediated contractility of isolated human resistance arteries
Authors: Nielsen H. , Hasenkam J. M. , Pilegaard H. K. , Aalkjaer C. , Mortensen F. V.
Published: December 2017

Human subcutaneous resistance arteries (122-298 microns), isolated from 139 patients undergoing surgery, were mounted in an isometric myograph. With the use of multiple regression analysis, five different modes of activation were examined for possible associations with age and mean arterial blood pressure of the patients: the contractile responses to 10 microM norepinephrine (mixed alpha 1-agonist/alpha 2-agonist), perivascular nerve stimulation, 10 microM phenylephrine (alpha 1-agonist), 100 microM B-HT 933 (alpha 2-agonist), and depolarization by potassium chloride. Blood pressure increased significantly with age. Blood pressure independently was not correlated to any mode of activation. With increasing patient age, however, responses to norepinephrine, phenylephrine, and perivascular nerve stimulation decreased, whereas the response to B-HT 933 increased; responses to potassium chloride were unaltered. Also corrected for changes in blood pressure, age independently was negatively correlated to the response to norepinephrine and phenylephrine, whereas a positive, though nonsignificant (P value = 0.12), correlation was observed between age independently and the response to B-HT 933. These data suggest that the ability of isolated human resistance arteries to evoke contractions medicated by postjunctional alpha 1-, but not alpha 2-adrenoceptors, decreases with age.
Muscarinic cholinergic receptors in canine adrenal gland
Authors: Tobin J. R. , Breslow M. J. , Traystman R. J.
Published: December 2017

Muscarinic cholinergic receptor stimulation has been reported to modulate adrenal catecholamine and steroid secretion and influence medullary vascular tone. The present study was undertaken to localize and characterize muscarinic cholinergic receptor binding sites in canine adrenal medulla and cortex. Binding studies using semipurified membranes demonstrated specific, saturable binding of L-[benzilic-4,4'-3H(N)]-quinuclidinyl benzilate ([3H]QNB) in medulla, with a dissociation constant (KD) equal to 152 pM and estimated maximal binding sites (Bmax) equal to 179 fmol/mg protein. Displacement of [3H]QNB by cholinergic agents in order of decreasing potency was atropine, pirenzepine, oxotremorine, pilocarpine, and carbamylcholine, suggesting the receptor was M1 subtype, similar to sympathetic ganglion muscarinic receptors. Autoradiographic imaging studies demonstrated highly specific, homogeneous binding throughout the medulla. No specific binding was found in adrenal cortex. These results suggest that muscarinic effects on blood flow may be neurally mediated, rather than the result of stimulation of vascular muscarinic receptors. In medulla, muscarinic receptors are evenly distributed and modulate catecholamine secretion in all cells rather than subpopulations of cells as in other species. Absence of [3H]QNB binding in cortex argues against muscarinic receptor modulation of cortical steroid secretion.
Different responses of extent and velocity of contraction to dobutamine in conscious sheep
Authors: Aoyagi T. , Fujii A. M. , Colan S. D. , Flanagan M. F. , Mirsky I.
Published: December 2017

The shortening- and shortening rate-preload-afterload relations, based on the concept of the myocardial end-systolic stress-strain relation (ESSSR), are a newly developed load- and size-independent assessment of myocardial contractility. The purpose of this study was to apply this assessment to compare extent and velocity of myocardial contraction during graded infusions of dobutamine. Seven chronically instrumented unsedated sheep were studied at rest and during graded infusions of dobutamine (2.5-20 micrograms.kg-1.min-1). The ESSSR were linear over a wide range of load alterations, whereas the end-systolic pressure-diameter relations (ESPDR) were generally nonlinear. Midwall shortening rate (SRm) at common preload and afterload representing contraction extent increased with each dose of dobutamine through 20 micrograms.kg-1.min-1. In contrast, midwall shortening (Sm) increased through dobutamine 5 micrograms.kg-1.min-1 but not at higher dobutamine infusion rates. Conventional endocardial shortening and the slope of the ESPDR, fitted to a linear model, exhibited responses similar to Sm. The velocity of circumferential endocardial fiber shortening (Vcf,c), Vcf,c-afterload relation, and maximum first derivative of left ventricular pressure exhibited responses similar to SRm. Thus both the extent and velocity of contraction increased at low doses of dobutamine, whereas only the velocity increased at high doses. Potential mechanisms for the saturated response of the extent of contraction include 1) shorter systolic time for contraction due to earlier onset of relaxation and 2) the utilization of myocardial contractile energy for left ventricular wall deformation at small cavity volumes at high doses of dobutamine.
Expression of Na(+)-K(+)-ATPase alpha 1- and alpha 3-isoforms in adult and neonatal ferret hearts
Authors: Ng Y. C. , Book C. B.
Published: December 2017

We have demonstrated previously that in adult ferret heart two alpha-subunit isoforms of the Na(+)-K(+)-ATPase, alpha(+) and alpha, are expressed. The alpha(+)-isoform may comprise either alpha 2-, or alpha 3-, or both isoforms. The present studies further characterize the alpha(+)-isoform. The alpha(+)-isoform of ferret heart did not react with an alpha 2-specific monoclonal antibody, but rather with two different alpha 3-specific polyclonal antibodies. Electrophoretic mobility of the alpha(+)-isoform in sodium dodecyl sulfate polyacrylamide gel electrophoresis is slower than that of the alpha 2-isoform, but similar to that of the alpha 3-isoform. Limited proteolytic peptide mapping was performed using Staphylococcus aureus V8. Proteolytic fragments were then immunostained with an alpha 3-specific antibody. The peptide maps of ferret heart alpha(+)-isoform and rat brain alpha 3-isoform were identical, as were those of ferret heart alpha(+)-isoform and ferret brain alpha 3-isoform. These results indicate that the alpha(+)-isoform of ferret heart is an alpha 3-isoform. During postnatal development, the same isoforms expressed in the adult ferret heart (alpha 1 and alpha 3), were also expressed in neonatal heart. In adult or neonatal heart alpha 2-isoform was not detectable. Relative abundances of the isoforms in ventricular and atrial tissues differed. Compared with ventricular tissue, left and right atrial tissues expressed much less alpha 3 than alpha 1. It is concluded that, unlike rat heart, alpha 1- and alpha 3-isoforms are expressed in adult ferret heart.(ABSTRACT TRUNCATED AT 250 WORDS)
cAMP and extrarenal vasopressin V2 receptors in dogs
Authors: Liard J. F.
Published: December 2017

The effect of vasopressin analogues on plasma adenosine 3',5'-cyclic monophosphate (cAMP) concentration was examined in a group of five conscious dogs instrumented for the measurement of arterial pressure and cardiac output (electromagnetic flowmeter). These dogs were infused for 20 min with a selective antidiuretic (V2) agonist, desamino-8-D-arginine vasopressin (DDAVP, 10 ng.kg-1 x min-1). This infusion was repeated on another day in the presence of the combined V1-V2 antagonist d(CH2)5-D-Tyr(Et)-4-valine,8-arginine vasopressin. The dogs also received an infusion of the selective V1 agonist 2-phenylalanine,8-ornithine oxytocin (Phe-OrnOT) at a rate of 10 ng.kg-1 x min-1. The effect of these infusions was compared with those of an isotonic saline infusion. Plasma cAMP measured in the aorta remained unchanged during all infusions but that of the selective V2 agonist DDAVP alone, during which it increased significantly from 22.4 +/- 0.8 to 32.6 +/- 4.6 and 37.0 +/- 4.1 pmol/ml after 10 and 20 min, respectively. In the plasma sampled from the inferior vena cava caudal to the renal veins, cAMP increased during DDAVP infusion from 22.2 +/- 2.5 to 39.2 +/- 3.8 and 36.0 +/- 4.0 pmol/ml after 10 and 20 min, respectively. The infusion of DDAVP was later given to the same dogs under anesthesia after bilateral nephrectomy, which did not modify the effect of DDAVP on arterial plasma cAMP. In another group of four conscious dogs, infusion of DDAVP at the same rate did not induce significant changes in plasma catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)
Small apex-to-base heterogeneity in radius-to-thickness ratio by three-dimensional magnetic resonance imaging
Authors: Beyar R. , Weiss J. L. , Shapiro E. P. , Graves W. L. , Rogers W. J. , Weisfeldt M. L.
Published: December 2017

Reported large base-to-apex differences in endocardial area ejection fraction may suggest large variability in myocardial function and load. To test ventricular load heterogeneities, we measured the ratio of radius of curvature to wall thickness (R/T), as a stress index reflecting myocardial load. End-diastolic (ED) and end-systolic (ES) magnetic resonance cross-sectional images were obtained in 15 open-chest dogs at 5 levels from base to apex, from which 4 three-dimensional thick disks were generated from adjacent image planes. The average R/T for each disk was calculated by planar and three-dimensional methods, using both midwall and endocardial radii of curvature. R/T was normalized to the apical value to quantify the relative changes in myocardial load. Normalized R/T using the midwall three-dimensional approach was 1.08, 1.11, 1.06, and 1.0 for ED (P = NS) and 1.25, 1.013, 1.08, and 1.0 for ES (P < 0.02), base to apex, respectively, while the other methods yielded higher values. Therefore, R/T calculated by the three-dimensional midwall approach shows only small apex-to base variations at ED (< 11%) and ES (< 25%), which is substantially less than the variability in area ejection fraction (102%). This suggests only small base-to-apex load heterogeneities, in spite of large changes in the area ejection fraction, an index reflecting specific ventricular geometry rather than local myocardial function.
Modulation of vascular tone in renal microcirculation by erythrocytes: role of EDRF
Authors: Imig J. D. , Gebremedhin D. , Harder D. R. , Roman R. J.
Published: December 2017

The effect of erythrocytes (red blood cells, RBC) on vascular tone in the renal microcirculation was examined using the juxtamedullary nephron microvascular preparation perfused in vitro with a physiological salt solution containing 5% albumin. The basal diameters of the arcuate, interlobular, proximal, and distal afferent arterioles averaged 444 +/- 24, 74 +/- 3, 29 +/- 1, and 19 +/- 1 micron, respectively, when perfused with a cell-free solution at a pressure of 80 mmHg. The diameters of the arcuate and interlobular arteries increased by 14 +/- 4 and 13 +/- 4%, respectively, whereas the diameter of the proximal and distal portions of the afferent arterioles decreased by 7 +/- 2% when perfusion pressure was elevated from 80 to 160 mmHg. The addition of RBC to the perfusate reduced the basal diameters of interlobular and afferent arterioles by 11 +/- 4 and 15 +/- 3%, respectively. The maximal vasoconstrictor response was seen after the addition of only 1% RBC to the perfusate. Removal of platelets did not block the vasoconstrictor response to addition of RBC to the perfusate. The role of endothelium-derived relaxing factor (EDRF) in the vasoconstrictor response to RBC was studied by addition of nitric oxide synthase inhibitor, N omega-nitro-L-arginine (L-NNA, 100 microM) to the perfusate. L-NNA reduced the basal diameters of interlobular and afferent arterioles by 7 +/- 3 and 9 +/- 3%, respectively, and abolished the vasoconstrictor response to RBC. L-NNA had no effect on the pressure-diameter relationships of the preglomerular vasculature when added to perfusates already containing RBC.(ABSTRACT TRUNCATED AT 250 WORDS)
Repeated reflection of waves in the systemic arterial system
Authors: Berger D. S. , Li J. K. , Laskey W. K. , Noordergraaf A.
Published: December 2017

Traditional analysis of pulse-wave propagation and reflection in the arterial system treats measured pressure and flow waves as the sum of a single forward wave (traveling away from the heart) and a single backward wave (traveling toward the heart). The purpose of this study was to develop a more general wave reflection theory that allows repeated reflection of these waves. The arterial system was modeled as a uniform viscoelastic tube terminating in a complex load with reflections occurring at the tube load interface and the heart tube interface. The resulting framework considers the forward wave to be the sum of an initial wave plus a series of antegrade waves. Similarly, the backward wave is the sum of a series of retrograde waves. This repeated reflection theory contains within it the traditional forward/backward wave reflection analysis as a special case. In addition, the individual antegrade and retrograde waves, at the tube entrance, are shown to be independent of the tube length. Aortic pressure and flow data, from dog experiments, were used to illustrate the phenomenon of repeated reflections. Alteration of the arterial system loading conditions, brought about through pharmacological intervention, affected the number and morphology of repeated waves. These results are compared with those found in traditional forward/backward reflection analysis.
Regional finite deformations of in situ canine pericardium
Authors: Chew P. H. , Humphrey J. D. , Yin F. C.
Published: December 2017

The purpose of this study was to determine in situ regional pericardial strains over a wide range of conditions. In five open-chest, anesthetized dogs we examined deformations from biplane cineradiographs of three sets of four 1-mm diameter steel beads glued to basal, midanterior, and apical regions of the pericardium during extremes of pericardial sac sizes (inferior vena caval occlusion, baseline, and tamponade). Finite deformation theory was used to determine the planar components of the Green's strains referenced to the completely unloaded, excised pericardium at the end of each experiment. From the Green's strains the principal components, EI and EII, and the principal direction of strain were determined. The first strain invariant, I1 = EI + EII, in the basal, anterior, and apical regions during caval occlusion (1.27, 0.73, and 0.67) did not differ significantly from those in the baseline state (1.43, 0.86, and 0.76) but increased significantly (P < 0.01) during tamponade to 1.54, 1.30, and 1.08, respectively. Using end systole during inferior vena cava occlusion as a reference, the directions of principal strain in each region during each condition were aligned parallel to the spine pointing toward the tail except at the base during tamponade when there was a 70 degree rotation toward the left limb. The in situ dog pericardium is considerably strained by the underlying heart even during inferior vena cava occlusion, suggesting that a completely unloaded state cannot be achieved in situ. The regional differences in the direction but not the value of principal strain suggest that there are either regional variations in loading or material properties.
Pressure-flow characteristics of intramural and total coronary collateral networks
Authors: Scheel K. W. , Mass H. , Williams S. E.
Published: December 2017

The purpose of the present investigation was to determine the pressure-flow (PF) relationship of intramural collaterals and to determine whether their characteristics differ significantly from those of the total collateral network, defined as the epicardial plus intramural collateral network. Because a significant portion of the collateral flow is diverted away from the retrograde flow measurement, we embolized the coronary vessel on which the retrograde flow was measured with spheres of various sizes until the retrograde flow was maximized and retrograde flow diversion blocked. The PF relationship was obtained before and after the epicardial collaterals were cauterized to determine the characteristics of the total and intramural collateral network. PF data for the collateral circulations were obtained by changing the inflow pressure to all coronary vessels simultaneously and by measuring the retrograde flow while maintaining the retrograde outflow pressure at 0 mmHg. The PF characteristics of the total and intramural collateral circulations could be fitted by either a second-degree polynomial or linear equation. In both cases the pressure intercept crossed the origin of the axes. The average contribution of intramural collaterals to total retrograde flow was 58 +/- 5%. We conclude that the PF characteristics of intramural collaterals parallel those of the total collateral circulation.
Microvascular pressure and albumin extravasation after leukocyte activation in hamster cheek pouch
Authors: Gawlowski D. M. , Benoit J. N. , Granger H. J.
Published: December 2017

The effects of leukotriene B4 (LTB4) and N-formyl-methionyl-leucylphenylalanine (FMLP) on transmicrovascular exchange of fluorescein isothiocyanate (FITC)-labeled serum albumin and dextran (molecular mass, 150,000 Da) were evaluated in hamster cheek pouch utilizing measurements of microvascular pressure and global efflux of the macromolecular markers into the tissue suffusate. Exposure of the suffused pouch to 1.0 microM LTB4 failed to alter microvascular pressure from its control level. The microvascular clearance of FITC-albumin rose to a peak value of 1.7 times the control value at a LTB4 concentration of 1.0 microM; the rate of albumin extravasation did not change from the normal level at a concentration of 0.1 microM. The extravasation rate of FITC-dextran was elevated with both doses of LTB4; the leukocyte chemotactic agent elicited 2.4- and 9.7-fold increments in peak clearance of dextran at concentrations of 0.1 and 1.0 microM, respectively. FMLP elicited a twofold increase in venular and terminal arteriolar pressures at a concentration of 1 microM; at the same concentration, the albumin clearance rose 3.5-fold. The results suggest that albumin transport remains near the normal level after LTB4 elicits massive migration of leukocytes across the venular membrane. By contrast, albumin transport is greatly accelerated following exposure to the chemotactic peptide FMLP; ultrastructural and physiological evidence suggests that the leakage of albumin is augmented by increases in microvascular permeability and filtration pressure. The results also reinforce previous ultrastructural observations from our laboratory indicating that diapedesis per se is not a cause of microvascular hyperpermeability in inflammatory reactions.
Contribution of wall mechanics to the dynamic properties of aortic baroreceptors
Authors: Imaizumi T. , Sugimachi M. , Harasawa Y. , Ando S. , Sunagawa K. , Hirooka Y. , Takeshita A.
Published: December 2017

To examine the contribution of wall mechanics to dynamic properties of baroreceptors, we subdivided the transfer function of baroreceptors into two subsystems [aortic pressure to diameter and diameter to aortic depressor nerve activity (ANA)]. In six alpha-chloralose-anesthetized rabbits, we measured pressure, diameter, and ANA while randomly perturbing pressure. We obtained transfer functions (pressure to ANA, diameter to ANA, and pressure to diameter) by taking the ratio of crosspower spectrum to the input power spectrum (0.005–5 Hz). Below 3 Hz, the transfer function from pressure to ANA was nearly identical to that from diameter to ANA, whereas that from pressure to diameter was flat. Using transfer functions we could reproduce adaptation and hysteresis that were quantitatively similar between pressure-ANA transduction and diameter-ANA transduction. The pressure-diameter relationship was almost instantaneous and thus showed no hysteresis. In a second group of rabbits, the ratio of the shift of the hysteresis loop was unchanged by ouabain (40 micrograms/kg iv, n = 7). We conclude that the dynamic properties of baroreceptors may not be related to the wall mechanics or the Na(+)-K(+)-adenosinetriphosphatase activity.
GABA modulates neurotransmission in sinus node via stimulation of GABAA receptor
Authors: Matsuyama S. , Saito N. , Shuntoh H. , Taniyama K. , Tanaka C.
Published: December 2017

The neuromodulator role of gamma-aminobutyric acid (GABA) in the sinus node of the guinea pig heart was examined. GABA inhibited the electrical transmural stimulation (ETS)-evoked release of [3H]norepinephrine (NE) from the sinus node. Muscimol mimicked and bicuculline antagonized the inhibitory effect of GABA. However, the ETS-evoked release of [3H]NE was not inhibited by muscimol in the presence of atropine. The ETS-evoked release of [3H]acetylcholine (ACh) from the sinus node was enhanced by muscimol, and this effect was antagonized by bicuculline. As the ETS-evoked release of [3H]ACh was reduced by bicuculline alone, the endogenous GABA released by ETS is probably involved in the release of ACh. We propose that GABA, as a neuromodulator, inhibits activity of the adrenergic neuron due to stimulation of the cholinergic neuron via the GABAA receptor present in the sinus node.
Neurohumoral modulators and sodium balance in experimental heart failure
Authors: Villarreal D. , Freeman R. H. , Johnson R. A.
Published: December 2017

The acute and chronic interactions of the renal nerves, atrial natriuretic factor (ANF), and mineralocorticoids for the regulation of sodium balance were examined in dogs with an arteriovenous (AV) fistula and the syndrome of high-output heart failure (HOHF) (n = 6). After the AV fistula and bilateral renal denervation, the animals avidly retained sodium for 5-7 days and then regained sodium balance for the subsequent 3 wk. This compensation was associated with the sustained elevations of plasma ANF and the normalization of plasma renin. Subsequent administration of deoxycorticosterone acetate (DOCA) for 10 days produced consistent sodium retention despite additional elevations in plasma ANF. All of these responses were similar to previous studies in AV fistula dogs with intact renal nerves. In a separate part of the study, the renal actions of acute synthetic ANF infusions were examined in these renal-denervated AV fistula dogs before and after DOCA. In the pre-DOCA experiments, ANF infusions at 15, 30, and 100 ng.kg-1.min-1 produced dose-related increases in urinary sodium excretion and significant elevations in creatinine clearance. In the presence of DOCA, urinary sodium excretion was markedly attenuated during identical ANF infusions. The composite results suggest that mineralocorticoids have an important modulatory role for the regulation of sodium balance in experimental HOHF. However, compared with earlier studies in compensated AV fistula dogs with intact renal nerves, the present studies demonstrate that blockade of efferent renal sympathetic nerve activity can restore the natriuretic expression of acute elevations in circulating ANF.