bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrically stimulated contraction accelerates protein synthesis rates in adult feline cardiocytes
Authors: Ivester C. T. , Kent R. L. , Tagawa H. , Tsutsui H. , Imamura T. , Cooper G. , McDermott P. J.
Published: December 2017

Cardiocytes were induced to contract via electrical field stimulation with an 8 V/cm electrical square-wave pulse of 5 ms at 0.125-2.0 Hz for up to 6 h. Protein synthesis rates were measured as rate of incorporation of [3H]-phenylalanine into total cell protein. Rates of protein synthesis were accelerated 43 +/- 4%, P < 0.001, by 4 h. The acceleration of total protein synthesis showed a frequency dependence between 0.125 and 0.5 Hz. In addition to accelerating rates of total protein synthesis, electrical stimulation of contraction accelerated fractional rates of synthesis of myosin heavy chain by 42 +/- 8%, P < 0.05. Protein synthesis rates were not accelerated upon electrical stimulation using subthreshold voltages. Addition of 100 ng/ml of actinomycin D had no effect on the ability of electrical stimulation of contraction to accelerate protein synthesis. To uncouple excitation-contraction coupling, 2,3-butanedione monoxime (BDM) was used to block actin-myosin cross-bridge interactions. BDM significantly decreased the ability of electrical stimulation to accelerate protein synthesis rates.
Superoxide anion production by rabbit thoracic aorta: effect of endothelium-derived nitric oxide
Authors: Pagano P. J. , Tornheim K. , Cohen R. A.
Published: December 2017

Rabbit thoracic aorta was assessed for the influence of the endothelium and nitric oxide (NO) on superoxide anion (SO) levels in the presence and absence of an inhibitor of superoxide dismutase. Aortic rings (0.5 cm) were incubated for 30 min at 37 degrees C in the presence or absence of diethyldithiocarbamate (DDC, 10 mM), a CuZn superoxide dismutase inhibitor. Rings were then placed in a solution containing lucigenin (250 microM) at 37 degrees C, and changes in amounts of SO over 10 min were determined by measuring chemiluminescence under basal and acetylcholine-stimulated conditions. Treatment with DDC markedly enhanced basal levels of SO, and the DDC-evoked levels were significantly reduced by the SO scavenger, Tiron (10 mM). Addition of acetylcholine (10 microM) to the assay did not significantly affect the levels of SO in either control or DDC-treated rings. Also, mechanical removal of the endothelium or pretreatment of the rings with the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) (300 microM), did not significantly affect the levels of SO in DDC-treated rings. In contrast, exogenous NO at 1 and 10 microM reduced the DDC-evoked SO levels by 54 and 77%, respectively. These data imply that the predominant sources of SO in the rabbit aorta are vascular components other than the endothelium and that endogenous superoxide dismutase modulates the level of SO. Although exogenous NO reduced aortic SO levels, neither basal nor acetylcholine-stimulated production of endogenous NO appears sufficient to reduce SO levels.
Validity of thermal dilution technique for measurement of cardiac output in rats
Authors: Kissling G. , Ross C. , Brandle M.
Published: December 2017

The validity of the thermal dilution technique for the measurement of cardiac output was verified in experiments on a circulation model and on anesthetized rats under open- and closed-chest conditions. In the circulation model thermal dilution was compared with direct (Fdir) and electromagnetic (F(elm)) flowmetry. Flow values measured in the circulation model with the thermal dilution (Fth) technique correspond well with direct flowmetry (Fth = 0.92 Fdir + 7.0; r = 0.888) and with electromagnetic flowmetry (Fth = 0.95 F(elm) + 1.2; r = 0.990). In the anesthetized rat cardiac output was determined with thermal dilution and simultaneously with Fick's method and/or with electromagnetic flowmetry. Fick's method and electromagnetic flowmetry resulted in identical cardiac output values (COFick = 0.95 COelm; r = 0.865), whereas the thermal dilution technique yielded unequivocally higher values. The extent of overestimation is much more pronounced at low cardiac output than at a high output. The study clearly demonstrates that this overestimation is due to heat diffusion, which is obviously of greater significance in small animals than in large animals or humans. Therefore, the thermal dilution technique is not appropriate for the measurement of cardiac output in the rat.
Differential actions of cAMP on endothelial [Ca2+]i and permeability in microvessels exposed to ATP
Authors: He P. , Curry F. E.
Published: December 2017

We investigated the hypothesis that one of the actions of adenosine 3',5'-cyclic monophosphate (cAMP) to attenuate agonist-induced increase in microvessel permeability is to reduce the initial increase in endothelial cell cytoplasmic Ca2+ concentration ([Ca2+]i). ATP (10 microM) was used to increase hydraulic conductivity (Lp) and [Ca2+]i in venular microvessel in frog mesentery. The cAMP analogue, 8-bromo-cAMP (8-BrcAMP, 2 mM) significantly attenuated the initial increase in Lp (from a peak increase of 7.1 +/- 2.4 times control with ATP alone to 1.2 +/- 0.34 times control with ATP and cAMP). In contrast, cAMP did not significantly change the magnitude or time course of the biphasic increase in [Ca2+]i, which increased from 54 +/- 5 nM to peak of 187 +/- 48 nM with ATP alone, and from 55 +/- 8 nM to 190 +/- 28 nM with ATP and cAMP. Thus the action of cAMP to attenuate microvessel permeability increase in the presence of ATP does not involve modification of the initial Ca2+ transient in endothelial cells. Our results enable alternative hypotheses, such as the suggestion that cAMP might modulate a Ca(2+)-calmodulin-dependent actin-myosin cascade, to be investigated without the added complications of having to account for the modulation of initial changes in [Ca2+]i. Our data also demonstrate, for the first time in the endothelial cells of intact microvessels, that an increase in [Ca2+]i is not always associated with an increase in microvessel permeability.
Variable effects of endothelin-1 on [Ca2+]i transients, pHi, and contraction in ventricular myocytes
Authors: Kohmoto O. , Ikenouchi H. , Hirata Y. , Momomura S. , Serizawa T. , Barry W. H.
Published: December 2017

We examined the effects of endothelin-1 (ET-1) on intracellular free calcium concentration ([Ca2+]i) transients, intracellular pH (pHi), and cell contraction in both embryonic and neonatal as well as in adult ventricular myocytes. Exposure of chick ventricular myocytes to ET-1 (10 nM) significantly decreased both peak systolic and end-diastolic [Ca2+]i (from 949 +/- 43 to 628 +/- 59 nM and from 230 +/- 13 to 162 +/- 8 nM, respectively; P < 0.05, n = 12). The amplitude of cell contraction was also decreased during exposure to 10 nM ET-1 (81.7 +/- 1.2% of control, P < 0.01, n = 12). Exposure to 10 nM ET-1 slightly decreased pHi (-0.055 +/- 0.020 U; P < 0.05). Exposure of cultured neonatal rat ventricular myocytes to ET-1 (10 nM) produced similar effects. Responses of adult rabbit ventricular myocytes to ET-1 were dramatically different from those of embryonic or neonatal ventricular myocytes. Exposure to 10 nM ET-1 increased the amplitude of cell contraction to 159 +/- 32% of control (P < 0.01) without an increase in [Ca2+]i transients. ET-1 also increased pHi (+0.081 +/- 0.047 U; P < 0.01). These results indicate that ET-1 produces a negative inotropic effect by decreasing [Ca2+]i transients and induces a slight intracellular acidosis in immature ventricular myocytes. However, ET-1 causes a positive inotropic effect in adult ventricular myocytes via an intracellular alkalinization, rather than by an increase in the [Ca2+]i transient. Thus the response of myocytes to vasoactive peptides may vary with development and/or species.
Use of 2,3-butanedione monoxime to estimate nonmechanical VO2 in rabbit hearts
Authors: Yaku H. , Slinker B. K. , Mochizuki T. , Lorell B. H. , LeWinter M. M.
Published: December 2017

The purpose of the present study was to evaluate the feasibility of partitioning myocardial O2 consumption (VO2) into mechanical and nonmechanical components in the whole heart preparation using a negative inotrope, 2,3-butanedione monoxime (BDM), which has been reported to have a selective effect on the contractile proteins in a low concentration range (< 6 mM). In six isolated bovine red blood cell-perfused rabbit hearts, VO2 and force-time integral (FTI) were measured during infusion of varying concentrations of BDM at a constant left ventricular volume chosen such that control left ventricular peak isovolumic pressure was approximately 100 mmHg. The VO2-FTI relation with BDM concentrations < or = 5 mM was highly linear (median r = 0.98). Its VO2-axis intercept at zero FTI had a positive value (mean 23% of control, 0.014 ml O2.beat-1 x 100 g-1). To confirm the selective effect of BDM on the contractile proteins, the intracellular free Ca2+ transient was measured with the fluorescent indicator indo 1 in three isolated buffer-perfused rabbit hearts. The amplitude of the Ca2+ transient was not altered by BDM at concentrations < or = 10 mM, although left ventricular developed pressure was markedly depressed. This finding indicates that BDM < or = 10 mM does not affect excitation-contraction coupling. We conclude that the VO2-axis intercept value of the VO2-FTI relation during BDM infusion in a low concentration range represents VO2 for nonmechanical energy utilization. The BDM method to partition VO2 into mechanical and nonmechanical components is thus feasible in the whole rabbit heart.
Changes in rat mesentery interstitial matrix due to superfusate
Authors: Barber B. J. , Babbitt R. A. , Dutta S. , Parameswaran S.
Published: December 2017

Animal preparations for microscopy often require a superfusate solution to cover surgically exposed tissue. There are few, if any, data concerning the effects of this solution on extravascular protein concentration and hydration. The effect of superfusion on mesenteric tissue in anesthetized male Sprague-Dawley rats was studied. Tissue samples were taken from nonsuperfused and superfused tissue and analyzed for hydration, albumin, and transferrin content. The mesenteric tissue interstitial matrix was rapidly altered by normal saline superfusate. After superfusion, there was a decrease (P < 0.01) in tissue albumin concentration from 1.17 +/- 0.27 to 0.10 +/- 0.08 g/dl (n = 9). Tissue hydration increased from 4.98 +/- 0.8 micrograms water/microgram dry wt in controls to 7.38 +/- 1.2 micrograms water/micrograms dry wt after superfusion. When a range of superfusate albumin concentrations was used (0, 1, 2, and 3 g/dl), tissue albumin concentration changed 0.59 +/- 0.09 g/dl for each gram per deciliter change in superfusate concentration (P < 0.0001). The large changes in interstitial matrix protein content and hydration suggest that superfusate solution effects need to be considered in microvascular protein transport experiments.
Carotid baroreflex responsiveness to lower body positive pressure-induced increases in central venous pressure
Authors: Shi X. , Potts J. T. , Foresman B. H. , Raven P. B.
Published: December 2017

Lower body positive pressure (LBPP) was applied at 4 and 30 Torr to increase central venous pressure (CVP). CVP increased with LBPP (r = 0.55, P < 0.01), and the increases were significant at 4 and 30 Torr (7.4 and 7.8 mmHg) from the control (6.0 mmHg). During LBPP cardiac output increased, which was significantly related to the increase in CVP (r = 0.63, P < 0.01). The carotid baroreflex was elicited by trains of neck pressure and suction from 40 to -65 Torr. The carotid-cardiac and carotid-vasomotor baroreflex responses were assessed by determining the maximal gains of heart rate (HR) interval and intraradial mean arterial pressure (MAP) to changes in carotid sinus pressure using a logistic model. The carotid-cardiac and carotid-vasomotor baroreflex gains were negatively related to LBPP, and at 30 Torr, both gains (5.6 ms/mmHg and -0.14 mmHg/mmHg) were significantly smaller than the control (12.4 ms/mmHg and -0.24 mmHg/mmHg). The decreases in carotid-cardiac and carotid-vasomotor baroreflex sensitivity during LBPP were primarily associated with the increases in CVP (r = -0.52, P < 0.01, and r = -0.74, P < 0.01, respectively). These data suggest that the increases in CVP and/or central blood volume diminish the sensitivity of the carotid baroreflex control of HR and MAP by enhancing the tonic inhibitory influence from the cardiopulmonary baroreceptors.
Release of vasoactive intestinal peptide and neuropeptide Y from canine heart
Authors: Anderson F. L. , Kralios A. C. , Reid B. , Hanson G. R.
Published: December 2017

The effects of right cervical vagal and left sympathetic stimulation on release of immunoreactive vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) into cardiac venous and lymphatic effluent was tested in 11 anesthetized adult mongrel dogs. After stimulation of the right cervical vagus (1 ms, 20 Hz, 5 V) for 3 min, VIP output in lymphatic effluent was significantly increased at 1.90 +/- 0.56 pg/min compared with control of 0.90 +/- 0.42 pg/min. NPY output in lymphatic effluent and VIP and NPY release into coronary venous effluent, as measured by the arterial-coronary sinus concentration difference, were not changed. After stimulation of the ansae of the left sympathetic ganglion (1 ms, 10 Hz, 5 V) for 3 min, NPY output in lymphatic effluent was significantly increased at 4.72 +/- 1.58 pg/min compared with a control of 0.73 +/- 0.66 pg/min. VIP output in lymphatic effluent was not changed. VIP arterial-coronary sinus concentration difference decreased slightly but significantly, and NPY arterial-coronary sinus concentration difference decreased markedly after left sympathetic stimulation. In three additional dogs in which coronary sinus blood flow was measured, NPY overflow during left sympathetic stimulation increased from 28.2 +/- 23.5 to 129.6 +/- 212.7 pg/min. Thus VIP and NPY release from the canine heart can be evoked by right cervical vagal and left sympathetic stimulation, respectively. VIP and NPY may play a role as cardiac noncholinergic-nonadrenergic neurotransmitters.
Adrenergic and pressure-dependent vascular regulation in sedentary and trained rats
Authors: Lash J. M. , Reilly T. , Thomas M. , Bohlen H. G.
Published: December 2017

In this study, we determined if aerobic exercise training alters adrenergic or pressure-dependent vascular regulation in the rat hindlimb or intestine. Pressor responses to bilateral carotid artery occlusion and systemic phenylephrine (PE) infusion were not altered by training. During occlusion, peak and steady-state changes in hindlimb vascular resistance (HLR) were significantly greater in trained (24 and 13%) than in sedentary (8 and -3%) rats; a similar trend existed for intestinal vascular resistance (IR). The pressure-dependent contribution was consistent between groups (HLR: peak 55-85%, steady state 25-45%; IR: peak and steady state 40-65%). During PE infusion, increases in IR and HLR were similar between groups. The increase in HLR was substantially pressure dependent in both groups (approximately 50% at highest dose) as was the change in IR in trained rats. However, the IR response to PE was not pressure dependent in sedentary rats. The direct effects of PE were similar between sedentary and trained rats in the hindlimb but were suppressed in the intestine of trained rats compared with sedentary rats. Therefore, aerobic exercise training altered adrenergic and pressure-dependent vasoregulatory mechanisms in both skeletal muscle and intestinal tissues.
Endothelium-derived contracting and relaxing factors contribute to hypoxic responses of pulmonary arteries
Authors: Kovitz K. L. , Aleskowitch T. D. , Sylvester J. T. , Flavahan N. A.
Published: December 2017

The response of porcine pulmonary arteries to hypoxia depended on their location in the vasculature and the degree and duration of the hypoxic challenge. In rings of pulmonary artery suspended for isometric tension recording (37 degrees C, 16% O2 and 5% CO2), moderate hypoxia (10% and 4% O2) caused endothelium-dependent relaxation in distal arteries but transient endothelium-dependent contraction in proximal arteries. In both proximal and distal arteries, the initial response to anoxia (0% O2) was a transient endothelium-dependent contraction. This was followed by a slowly developing, sustained endothelium-dependent contraction in proximal arteries, or by an endothelium-independent relaxation in distal arteries. The endothelium-dependent relaxation to moderate hypoxia in distal arteries was inhibited only by combined inhibition of endothelium-derived relaxing factor (EDRF)-nitric oxide (NO) synthase [N omega-nitro-L-arginine methyl ester (L-NAME)] and cyclooxygenase (indomethacin), suggesting mediation by EDRF-NO and prostacyclin. Transient endothelium-dependent contractions to moderate hypoxia (proximal arteries) or anoxia (all arteries) were abolished by L-NAME, but the late endothelium-dependent anoxic contraction observed in proximal arteries was not reduced by L-NAME and/or indomethacin. Therefore, hypoxia/anoxia may initiate contraction of pulmonary arteries by decreasing the activity of EDRF-NO, but the contractions appear to be maintained by an increased activity of an endothelium-derived contracting factor.
Arterial baroreceptors and brain histamine contribute to bradycardia to peripheral hyperosmolality
Authors: Kenney M. J. , Bealer S. L.
Published: December 2017

The purpose of this study was to determine whether the bradycardic response to peripheral hyperosmolality in conscious rats is dependent on afferent baroreceptor mechanisms and whether central histamine H2 receptors play a role in baroreflex-mediated changes in heart rate (HR). Mean arterial pressure (MAP) and HR were recorded continuously during a 30-min infusion of 2.5 M NaCl (10 microliters.100 g-1.min-1) hypertonic saline (HTS). HTS infusion significantly increased MAP (21 +/- 4 mmHg) and reduced HR (-62 +/- 10 beats/min) in rats with intact arterial baroreceptors. In sinoaortic-denervated rats, HR remained unchanged from control despite a significant increase in MAP. After intracerebroventricular (lateral ventricle) administration of cimetidine or ranitidine (H2-receptor antagonists) in intact rats, HTS infusion significantly increased MAP (19 +/- 2 and 17 +/- 2 mmHg, respectively) but the bradycardia was abolished (-12 +/- 10 and -10 +/- 10 beats/min, respectively). In contrast, central H2-receptor blockade did not alter reflex HR responses to the intravenous administration of phenylephrine and nitroprusside or to the central administration of histamine or angiotensin II. These results indicate that the bradycardic response to HTS infusion is mediated through the arterial baroreceptor reflex and involves in part a selective histaminergic pathway.
Kallikrein release by vascular tissue
Authors: Nolly H. , Carretero O. A. , Scicli A. G.
Published: December 2017

Vascular tissue contains kallikrein and kallikrein mRNA, suggesting a vascular kallikrein-kinin system. We questioned whether 1) kallikrein concentration varies among large and small vessels; 2) kallikrein is released by vascular tissue; and 3) blocking protein synthesis inhibits release, suggesting de novo synthesis. Using rat vascular rings and isolated-perfused hindquarters, we examined kallikrein in the bath and perfusate. Active kallikrein was higher in tail arteries than the aorta (P < 0.001); tail veins had six times more kininogenase than the vena cava (P < 0.001). Total kallikrein showed a similar pattern, being highest in tail vessels. Arterial rings released active and total kallikrein. After 1, 2, and 3 h incubation, cumulative release was as follows: active, 90 +/- 13, 201 +/- 25, and 311 +/- 41 pg.h-1 x mg tissue-1; total, 170 +/- 14, 366 +/- 24, and 537 +/- 40 pg.h-1 x mg tissue-1, indicating constant release up to > or = 3 h. In contrast, lactic dehydrogenase fell from 6.7 +/- 2.5 to 2.5 +/- 0.4 U.h-1 x mg tissue-1. Total kallikrein in the rings was 302 +/- 51 pg bradykinin/mg wt tissue before 3 h and 298 +/- 68 afterward. Kallikrein released by the hindquarters after 3 h was as follows: active, 6.2 +/- 2.8 ng bradykinin.min-1 x kg.body wt-1; total, 85.2 +/- 17 ng bradykinin.min-1 x kg body wt-1. Puromycin pretreatment (10 mg ip) reduced total perfusate kallikrein from 105 +/- 19 to 8.5 +/- 3.6 (P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
Local cerebral blood flow and glucose utilization after blood exchange with a hemoglobin-based O2 carrier in conscious rats
Authors: Waschke K. , Schrock H. , Albrecht D. M. , van Ackern K. , Kuschinsky W.
Published: December 2017

The effects of a blood exchange on cerebral blood flow and glucose utilization were studied. A near to total blood exchange (hematocrit < 3%) was achieved in conscious rats by isovolemic hemodilution. Ultrapurified, polymerized, bovine hemoglobin (UPBHB) served as a blood substitute. Local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were measured in 34 brain structures of conscious rats by means of the ido[14C]antipyrine and the 2-[14C]-deoxy-D-glucose methods. A group of rats without blood exchange served as control. After blood exchange LCBF increased from 36 to 126% in the different brain structures resulting in a nearly doubled mean cerebral blood flow (+82%). LCGU increased only moderately by 0-24%. Significant increases in LCGU were observed in 16 brain structures. Mean cerebral glucose utilization slightly increased (+14%). The relationship between LCGU and LCBF was found to be tight both in the control group (r = 0.95) as well as after blood replacement (r = 0.94), although it was reset to a higher overall LCBF-to-LCGU ratio. The profound increases in LCBF observed after blood exchange, which were not paralleled by comparable increases in LCGU, might be explained by a reduction of blood viscosity after blood exchange. Additional effects of blood exchange observed in the present study were an increase of mean arterial blood pressure and a decline of heart rate. The results indicate that replacement of blood with the hemoglobin-based oxygen carrier UPBHB appears to meet the cerebral circulatory and metabolic demands of the brain tissue.
Adenosine contributes to hypoxia-induced vasodilation through ATP-sensitive K+ channel activation
Authors: Nakhostine N. , Lamontagne D.
Published: December 2017

the relative contribution of adenosine and ATP-sensitive potassium (KATP) channels in hypoxia-induced vasodilation was studied in isolated, saline-perfused rabbit hearts under constant flow conditions. Adenosine infusion induced a dose-dependent reduction in coronary perfusion pressure. Inhibition of KATP-channels with glibenclamide (0.3 microM) significantly reduced the dilator response to adenosine (-26 +/- 6 ys. -6 +/- 2% at 1 microM), whereas those of 1 microM acetylcholine or 10 microM papaverine were unaffected. The dilator responses to the A1-receptor selective agonist, N6-cyclopentyladenosine (CPA), and the mixed A1- and A2-receptor agonist, 5'-(N-ethylcarboxamido) adenosine (NECA), were comparable to that of adenosine. Treatment with glibenclamide reduced partially but significantly the NECA-induced vasodilation (-28 +/- 4 vs. -17 +/- 4%) and changed the CPA dilator response to a significant vasoconstriction. Both the nonselective adenosine-receptor antagonist, 8-phenyltheophylline (10 microM), and glibenclamide blocked the dilator response to adenosine and significantly reduced the hypoxia-induced vasodilation to the same extent. In conclusion, we suggest that the activation of KATP channels plays a major role in hypoxia-induced vasodilation. A major part of this activation results from the action of adenosine on receptors closely related to the A1 type.
A comparison of cyclopiazonic acid and ryanodine effects on cardiac muscle relaxation
Authors: Pery-Man N. , Chemla D. , Coirault C. , Suard I. , Riou B. , Lecarpentier Y.
Published: December 2017

We investigated cardiac muscle behavior after inhibition of either sarcoplasmic reticulum (SR) Ca2+ release or SR Ca2+ uptake. Mechanics of 35 rat papillary muscles were studied after either ryanodine 10(-7) M (n = 11) or cyclopiazonic acid (CPA) 10(-5) M (n = 14) and compared with a control group containing the solvent alone (n = 10). We measured the maximum extent of shortening (delta L) of the preloaded twitch (delta Lp), and the normalized total force (TF) of the full isometric twitch (TFi). The peak lengthening velocity (Vl) of the preloaded twitch (Vlp) and the normalized negative peak force derivative of the fully isometric twitch (-DFi) tested the lusitropic state. With the influence of shortening and/or load on relaxation taken into account, analysis of relaxation was performed using 1) Vlp-to-delta Lp and magnitude of -DFi-to-TFi ratios and 2) slopes of the Vl-delta L and magnitude of -DF-TF relationships over the entire continuum of load. Ca(2+)-release inhibition with ryanodine induced a negative inotropic effect and a decrease in Vlp from 2.7 +/- 0.2 to 1.4 +/- 0.2 Lmax/S, where Lmax is the initial length at the peak of the length-active tension curve (P < 0.001). The Vlp-to-delta Lp ratio and the slope of the Vl-delta L relationship were preserved, indicating that ryanodine was devoid of intrinsic relaxant effect under isotonic conditions. Ca(2+)-uptake inhibition with CPA had no inotropic effect but decreased Vlp from 2.9 +/- 0.1 to 2.2 +/- 0.1 Lmax/s (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Connections between the pontine reticular formation and rostral ventrolateral medulla
Authors: Krassioukov A. V. , Weaver L. C.
Published: December 2017

Pontine reticular formation (PRF) neurons provide tonic excitatory drive to sympathetic nerves and are involved in cardiovascular control [K. Hayes and L. C. Weaver. Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H1567-H1575, 1992]. However, connections between the PRF and the well-known vasomotor region in the rostral ventrolateral medulla (RVLM) are unknown. In propofol (Diprivan)- anesthetized rats we investigated arterial pressure, heart rate, and renal nerve responses to microinjection of glycine (1.0 M, 60 nl) into the PRF before and after injection of the synaptic blocking agent cobalt chloride (4.0 mM, 200 nl) into the RVLM. Glycine injections into the PRF caused decreases in arterial pressure, heart rate, and discharge of renal sympathetic nerves. Synaptic blockade of the RVLM almost eliminated cardiovascular and sympathetic responses to glycine injections into the PRF and blocked somatosympathetic reflexes in the renal nerve. Cobalt injections into the RVLM had very small effects on basal renal nerve firing, arterial pressure, or heart rate. These results suggest that the neurons within the RVLM relay influences from the PRF to sympathetic preganglionic neurons. Because injections of the excitatory amino acid antagonist, kynurenate, into the RVLM also interrupted responses to blockade of the PRF and blocked somatosympathetic reflexes, glutamate is a likely neurotransmitter from the PRF to the RVLM and for somatosympathetic reflexes.
Neuropeptide Y infusion improves hemodynamics and survival in rat endotoxic shock
Authors: Hauser G. J. , Myers A. K. , Dayao E. K. , Zukowska-Grojec Z.
Published: December 2017

Neuropeptide Y (NPY), a sympathetic and platelet-derived vasoconstrictor, acts both directly and by potentiating adrenergic responsiveness and therefore may be beneficial in endotoxic shock, where suppressed vascular responsiveness to adrenergic agents is a key factor. This was studied in anesthetized rats. First, infusion of a nonhypotensive dose of endotoxin (lipopolysaccharide, LPS) markedly suppressed the pressor response to increasing doses of norepinephrine (NE), angiotensin II, and vasopressin but did not suppress the response to NPY. Second, in rats rendered hypotensive by intravenous LPS, continuous NE infusion (0.1-1.0 microgram.kg-1 x min-1 started 5 min after LPS for 1 h) did not alter hemodynamics. In contrast, 5 nmol.kg-1 x min-1 of NPY (equipotent to 0.1 microgram.kg-1 x min-1 of NE in normal rats) increased mean arterial pressure (MAP, from 64 to 114% of baseline), total peripheral resistance index (TPRI, from 64 to 154% of baseline), and left ventricular stroke work index (from 36 to 73% of baseline), without changing cardiac index (CI). Third, in a similar experimental protocol, pretreatment of the hypotensive rats with phentolamine blocked the pressor effect of NE infusion, but only partially attenuated the response to NPY. Finally, addition of low-dose NPY to NE infusion improved survival following a lethal dose of LPS compared with treatment with NE alone (P < 0.01). Thus, unlike other vasoconstrictors tested, NPY-mediated vasoconstriction is preserved during endotoxemia. The beneficial effect of NPY is mediated by increased TPRI without reduction in CI; both NPY receptor-mediated vasoconstriction and potentiation of adrenergic responsiveness may be involved.
Loss of hypoxic pulmonary vasoconstriction in chronic pneumonia is not mediated by nitric oxide
Authors: McCormack D. G. , Paterson N. A.
Published: December 2017

In pulmonary inflammatory processes such as pneumonia there is diminished hypoxic pulmonary vasoconstriction (HPV). We investigated whether the attenuated HPV in pneumonia is a due to excess nitric oxide (NO) release. Sprague-Dawley rats were anesthetized, and a slurry (0.06 ml) of infected agar beads (containing 6 x 10(5) Pseudomonas aeruginosa organisms) or control (sterile) beads was then injected into a distal bronchus through a tracheotomy. After the establishment of a chronic P. aeruginosa pneumonia (7-10 days later) animals were instrumented for hemodynamic monitoring, and the response to exposure to hypoxic gas (fraction of inspired O2 = 0.08) was recorded before and after the administration of NG-monomethyl-L-arginine (L-NMMA; 50 mg/kg), an inhibitor of NO synthesis. The hypoxic pressor response, as assessed by the absolute increase in pulmonary arterial pressure (PAP) and total pulmonary resistance (TPR), was reduced in infected animals compared with control animals. The change in PAP and TPR was 8.5 +/- 0.7 and 0.053 +/- 0.007, respectively, in control animals compared with 5.9 +/- 0.5 and 0.041 +/- 0.011 in infected animals. After L-NMMA the increase in PAP and TPR during hypoxia was greater in both control and infected animals. However, treatment with L-NMMA did not affect the difference between control and infected animals. We conclude that excess release of NO does not account for the attenuated hypoxic pressor response in pneumonia.
Renin-angiotensin system and minoxidil-induced cardiac hypertrophy in rats
Authors: Ruzicka M. , Leenen F. H.
Published: December 2017

Besides cardiac volume overload, cardiac sympathetic activity and the renin-angiotensin system (RAS) are activated by arterial vasodilators such as minoxidil. To evaluate the possible involvement of the RAS in the development of minoxidil-induced cardiac hypertrophy, we assessed in normotensive rats minoxidil-induced changes in cardiac and plasma renin activity (PRA) and the potential of chronic treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril and the nonpeptide angiotensin II receptor blocker losartan to prevent minoxidil-induced cardiac hypertrophy. PRA increased in parallel with the increase in cardiac filling pressures and development of cardiac hypertrophy, whereas the increase in cardiac renin activity was delayed as compared with these changes. Losartan did not decrease left ventricular end-diastolic pressure (LVEDP) but prevented the remodeling of the heart by minoxidil. In contrast, enalapril nearly normalized LVEDP but did not affect the hypertrophic response of the heart. The losartan data indicate that the RAS is involved in the minoxidil-induced cardiac hypertrophy either directly (e.g., by mediating the hypertrophic response of the heart to cardiac volume overload) or indirectly (e.g., by potentiating cardiac sympathetic activity). The ineffectiveness of enalapril has no obvious explanation but may possibly indicate ineffective blockade of angiotensin II formation in the heart in this model.
Fractal structure underlying patterns of premature heart beats
Authors: De Paola R. , Wang H. X. , Norwood W. I.
Published: December 2017

Distinctive patterns of premature heart beats are frequently observed in clinical data, yet transitions from one pattern to another often appear to occur unpredictably. In this study we investigate the origins of this apparent lack of long-term order by processing the time intervals between successive R wave features of the electrocardiogram to obtain a symbolic description of all characteristic patterns of premature beats observed in a clinical data set. These characteristic patterns are found to be 1) associated with fixed ranges of heart rate over periods of many hours and 2) organized into an interwoven fractal structure that corresponds to the sequence of mode-locked states predicted by a nonlinear mathematical model. The apparent randomness of transitions from one pattern to another results from the normal fluctuations in heart rate which can sample many such patterns on a minute-by-minute basis.
Myocardial metabolism in chronic reperfusion after nontransmural infarction in pig hearts
Authors: Liedtke A. J. , Renstrom B. , Nellis S. H. , Subramanian R. , Woldegiorgis G.
Published: December 2017

The purpose of these studies was to evaluate metabolic behavior in a 4-day reperfusion model in pigs after induction of subendocardial infarction. Two groups of swine [sham and intervention (Int) groups, n = 7) and 10 hearts per group, respectively] were prepared comparably with two surgical procedures separated over 4 days. In the Int group at the time of the first surgery, coronary flow in the left anterior descending (LAD) circulation was partially restricted (by 60%) for 60 min and was then reperfused. LAD myocardium at the time of the second surgery in both groups was extracorporeally perfused aerobically (5.9 +/- 0.2 ml.min-1.g dry wt-1) for 60 min and infused by equilibrium labeling with [U-14C]-palmitate and [5-3H]glucose to estimate fatty acid oxidation and exogenous glucose utilization. During extracorporeal perfusion, regional myocardial shortening and oxygen consumption were comparable between groups despite a marginal impairment in ATP resynthesis by mitochondria (26% decrease, P < 0.071) in Int hearts and a significant decline in mitochondrial respiration (45% decrease in respiratory control rate, P < 0.008; and 41% decrease in state 3 respiration, P < 0.032) as compared with sham hearts. Fatty acid oxidation described by 14CO2 production was 34.00 +/- 4.72 mumol.h-1.g dry wt-1 (averaged from 30-60 min of perfusion) in sham hearts but was decreased (by 48%, P < 0.004) in Int hearts. This reduction in fatty acid utilization may in part be explained by declines in the observed activity of the mitochondrial membrane transporter enzyme, carnitine palmitoyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)
Left ventricular unloading decreases rate of isovolumic right ventricular pressure decline
Authors: Brown C. D. , Chow E. , Farrar D. J.
Published: December 2017

To determine whether direct ventricular interaction affects right ventricular (RV) relaxation, we compared the minimum rate of change of RV pressure (dP/dtmin) and the time constant, tau, of isovolumic RV pressure decline in open-chest, anesthetized pigs following a normal left ventricular (LV) contraction and an acutely unloaded LV contraction. Rapid removal of blood via the LV apex into a prosthetic ventricle during a single systole decreased the LV pressure-time integral 68.3% and peak systolic pressure 49.9% without changing RV end-diastolic conditions. Micromanometers measured ventricular chamber pressures during single RV isovolumic beats, which were produced by transient pulmonary artery occlusion in both the control and the LV-unloaded states. When the LV was unloaded, RV tau rose significantly from 41.7 +/- (SD) 7.1 to 49.8 +/- 9.4 ms, P < 0.005 (pericardium intact) and 42.9 +/- 10.8 to 51.8 +/- 13.9 ms, P < 0.005 (pericardium opened). Simultaneously, RV dP/dtmin decreased from -400.5 +/- 136.6 to -288.3 +/- 46.8 mmHg/s, P = 0.14 (pericardium intact), and -342.4 +/- 104.2 to -241.2 +/- 118.9 mmHg/s, P < 0.01 (pericardium opened). These data indicate that LV systolic unloading decreases the rate of RV relaxation. We conclude that RV relaxation is influenced by direct anatomic ventricular interaction.
Venoconstriction to endothelin-1 in humans: role of calcium and potassium channels
Authors: Haynes W. G. , Webb D. J.
Published: December 2017

Recent studies in vitro have suggested that there may be an interaction between endothelin-1 and ATP-sensitive K+ channels in vascular smooth muscle. Here we have investigated whether agents acting on membrane Ca2+ and K+ channels modulate endothelin-1-induced venoconstriction in vivo in human subjects. In a series of studies, six healthy subjects received, on separate occasions, local infusions into dorsal hand veins of endothelin-1 coinfused with 1) the ATP-sensitive K+ channel opener, cromakalim; 2) the dihydropyridine Ca2+ antagonist, nicardipine; 3) a control vasodilator, hydralazine; and 4) saline placebo. Endothelin-1 caused local venoconstriction with a maximum reduction in vein size of 66 +/- 4% at 60 min (P = 0.0001 vs. basal). Cromakalim prevented endothelin-1-induced venoconstriction (9 +/- 10% maximum constriction; P = 0.68 vs. basal). By contrast, nicardipine, in a dose sufficient to block depolarization-induced constriction caused by K+ infusion, had only a partial effect on endothelin-1-induced venoconstriction (35 +/- 8% maximum constriction; P = 0.001 vs. basal; P = 0.02 vs. endothelin-1), whereas a 10-fold higher dose of nicardipine had no additional effect and hydralazine had no effect. In further studies, cromakalim, but not nicardipine, reversed endothelin-1-induced venoconstriction. Cromakalim did not prevent constriction induced by norepinephrine. Although calcium entry through dihydropyridine-sensitive Ca2+ channels may account in part for the vasoconstrictor action of endothelin-1 in humans, the abolition of endothelin-1 responses by a K+ channel opener suggests additional mechanisms of action for endothelin-1.
C5a-induced myocardial ischemia: role for CD18-dependent PMN localization and PMN-platelet interactions
Authors: Fletcher M. P. , Stahl G. L. , Longhurst J. C.
Published: December 2017

Intracoronary C5a in swine decreases coronary blood flow and regional myocardial segment shortening, responses mediated by thromboxane (Tx) A2-induced coronary vasoconstriction and intramyocardial trapping of granulocytes (PMNs). We sought to determine the origin of TxA2 and to investigate the role of CD18-dependent PMN function by utilizing an anti-CD18 monoclonal antibody, IB4. Isolated C5a-stimulated PMNs or platelets did not produce TxB2. However, together, C5a-stimulated PMNs and platelets produced TxB2. IB4 bound porcine PMN surface CD18 and blocked C5a-induced PMN functions. In vivo, IB4 loading (2 mg/kg) transiently decreased arterial blood pressure and circulating platelet counts in six of nine animals (390 +/- 31 vs. 176 +/- 41 X 10(6)/ml, control vs. IB4; P < 0.002) and significantly ameliorated C5a-induced decreases in coronary venous PMN count (-4.1 +/- 0.6 vs. -1.4 +/- 0.8 X 10(6) cells/ml), coronary artery blood flow (-10 +/- 1 vs. -4 +/- 1 ml/min), and segment shortening (-15 +/- 2 vs. -8 +/- 2%, C5a vs. C5a + IB4). We conclude that 1) production of TxB2 in response to C5a is mediated by a PMN-platelet interaction, 2) IB4 functionally blocks CD18 on porcine PMNs, and 3) C5a-induced myocardial PMN extraction is mediated, in part, by a CD18-dependent mechanism. These results suggest that PMN-platelet interactions and CD18-dependent PMN extraction are important in C5a-induced myocardial ischemia.
Inhibitory role of capsaicin-sensitive afferent neurons and nitric oxide in hemostasis
Authors: Lippe I. T. , Sametz W. , Sabin K. , Holzer P.
Published: December 2017

Capsaicin-sensitive afferent neurons control blood flow via release of peptide transmitters and formation of nitric oxide (NO). The present study examined whether capsaicin-sensitive afferent neurons and NO interact in the control of hemostasis. Afferent nerve ablation by pretreating rats with a neurotoxic dose of capsaicin (125 mg/kg) led to a 26% reduction of the time of bleeding from punctured small mesenteric arteries in pentobarbital-anesthetized animals. Blockade of NO formation by NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg) attenuated the bleeding time in capsaicin-pretreated rats but had no effect in vehicle-pretreated rats. Platelet aggregation induced by ADP was significantly augmented by 12% in capsaicin-pretreated rats. L-NAME did not alter platelet aggregation in vehicle-pretreated rats but enhanced it in capsaicin-pretreated animals. The prothrombin and partial thromboplastin time and the plasma levels of fibrinogen and antithrombin III remained unchanged by capsaicin or L-NAME, whereas the thrombin time was reduced in capsaicin-pretreated rats. These data indicate that capsaicin-sensitive afferent neurons play an inhibitory role in platelet aggregation and hemostasis, a function in which they interact with the NO system.
Cardiac desensitization to adenosine analogues after prolonged R-PIA infusion in vivo
Authors: Lee H. T. , Thompson C. I. , Hernandez A. , Lewy J. L. , Belloni F. L.
Published: December 2017

To determine the effects of chronic in vivo stimulation of adenosine receptors, R-(-)-N6-(2-phenylisopropyl)adenosine (R-PIA), a selective A1 receptor agonist, was administered to rats as a continuous 7-day infusion (200 nmol/h). Inotropic and chronotropic responses of isolated atria to adenosine receptor agonists were markedly desensitized compared with the responses of atria from age-matched control animals. Carbachol's negative chronotropic effect was also attenuated, indicating a heterologous mode of desensitization. Antagonist radioligand binding assays indicated a 52% reduction in A1 adenosine receptor maximum binding, and competition binding assays revealed a significant loss of G protein-coupled high-affinity A1 receptors in atria from R-PIA-treated rats. Inhibitory G proteins (Gi) were significantly reduced, as quantified by immunoblot analysis, with no change in the amount of stimulatory G proteins. Ventricular membranes from R-PIA rats showed loss of Gi and uncoupling of A1 receptors, without a significant change in A1 receptor density. Thus chronic R-PIA infusion desensitized rat atrial muscle to the effects of adenosine receptor agonists via several regulatory adaptations, including downregulation of A1 adenosine receptors, uncoupling of A1 receptors from their associated G proteins, and loss of Gi proteins.
Cytosolic calcium transients in myocytes isolated from rats with ischemic heart failure
Authors: Capasso J. M. , Li P. , Anversa P.
Published: December 2017

Mechanical performance and cytosolic Ca2+ dynamics were characterized in myocytes isolated from left and right ventricles of rats with ischemic heart failure. Seven days after coronary artery narrowing (CAN) in rats filling pressures were elevated, whereas systolic pressures and ejection of blood were depressed. Left ventricular myocytes increased 18% in length and 19% in width, whereas right myocytes expanded longitudinally by 23% and transversely by 24%. Contractile behavior of myocytes displayed reductions in myocyte shortening and velocity of shortening, despite prolongation of time to peak shortening. Diastolic Ca2+ increased by 32 and 39% in left and right myocytes of CAN animals, whereas peak systolic Ca2+ in left ventricular myocytes was depressed (22%). Time to peak Ca2+ was prolonged by 68% in left myocytes. Moreover, time required for peak Ca2+ to return to diastolic levels was prolonged in left myocytes. Regression analysis revealed correlations between end-diastolic pressure and diastolic Ca2+ and peak developed pressure and systolic Ca2+. Thus ischemic heart failure finds its cellular basis in a depression in myocyte contractility that may in turn be due to alterations in cytosolic Ca2+ handling.
Cyclic nucleotides and cerebrovascular tone in newborn pigs
Authors: Parfenova H. , Shibata M. , Zuckerman S. , Mirro R. , Leffler C. W.
Published: December 2017

Relationships between cyclic nucleotides and cerebrovascular tone were investigated using closed cranial windows in anesthetized newborn pigs. Pial arteriolar diameter was monitored and cerebrospinal fluid (CSF) was collected from beneath the cranial window. Adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) concentrations in CSF were 1,690 +/- 200 and 730 +/- 40 fmol/ml, respectively. Topically applied isozyme-selective and nonselective inhibitors [3-isobutyl-1-methylxanthine (IBMX), theophylline, Ro 201724, dipyridamole, zaprinast, calmidazolium, and W-7] of cyclic nucleotide phosphodiesterases dilated pial arterioles with concomitant increases in cAMP and/or cGMP levels in CSF. Topical application of dibutyryl-cAMP and dibutyryl-cGMP also resulted in pial arteriolar dilation. Ten-minute hypercapnia, which results in pial arteriolar dilation, increased cAMP to 5,240 +/- 900 and cGMP to 1,350 +/- 200 fmol/ml. IBMX and zaprinast potentiated the increases in cAMP and cGMP as well as the cerebrovascular dilation in response to hypercapnia. These data suggest that cyclic nucleotides contribute to regulation of cerebral vascular tone during control conditions. Furthermore, cAMP and/or cGMP appears to be involved in arterial vasodilation in response to hypercapnia in newborn pigs.
ANP has no postsynaptic effect on autonomic regulation of cardiac pacemaker rate in the rat
Authors: Atchison D. J. , Pennefather P. S. , Ackermann U.
Published: December 2017

We studied whether atrial natriuretic peptide (ANP) influences sinoatrial node pacemaker activity or whether it modifies the response to activation of postsynaptic autonomic receptors. Male Sprague-Dawley rats were anesthetized with pentobarbital sodium (45 mg/kg). Their hearts were removed quickly and placed in physiological salt solution. The atria were isolated; the right intra-atrial chamber was exposed to allow intracellular recording from sinoatrial node pacemaker cells. The tissue was placed in a temperature-regulated recording chamber and superfused with warmed oxygenated physiological salt solution. With use of standard microelectrode recording techniques, action potentials were recorded from spontaneously depolarizing cells in the presence of muscarine (62.5–500 nM) or norepinephrine (0.1 and 1.0 microM). Muscarine reduced the frequency of action potentials dose dependently, whereas norepinephrine increased their frequency. The addition of ANP (0.1–100 nM) to the superfusion had no effect on the frequency of action potentials during the superfusion of physiological salt solution or in the presence of either muscarine or norepinephrine. We conclude that ANP does not act on cardiac pacemaker cells to modulate the effect of neurotransmitters.