bluuebunny/crossref_metadata_2025 huggingface dataset:
Sympathetic activation induces asynchronous contraction in awake dogs with regional denervation
Authors: Knight D. R. , Shen Y. T. , Thomas J. X. , Randall W. C. , Vatner S. F.
Published: December 2017

To determine effects of regional left ventricular (LV) denervation on regional contractile responses to sympathetic activation, dogs with posterior LV wall denervation (posterior wall-denervated group) and dogs with innervated posterior LV walls (intact group) were studied during excitement, exercise, bilateral sympathetic nerve stimulation, and norepinephrine infusion. In intact conscious dogs, all modes of sympathetic activation increased the magnitude and decreased the time of onset of systolic wall thickening (WT) similarly in the anterior and posterior wall. In the denervated group, excitement failed to increase posterior WT during systole but instead elicited asynchronous contraction, i.e., postsystolic WT, as well as delayed onset of contraction. Asynchronous contraction was not observed with excitement after beta-adrenergic receptor blockade. Asynchronous contraction of the posterior wall was also observed during the initial phase of exercise in conscious dogs and during bilateral stellate stimulation in anesthetized dogs in the posterior wall-denervated group. In comparison to neural activation, adrenergic receptor activation with norepinephrine (0.2 microgram/kg-1.min-1 iv) induced a supersensitive increase in systolic WT in the denervated posterior wall (36 +/- 5%) compared with the anterior wall (17 +/- 2%) and a delay in the end of contraction in the anterior region. Thus asynchronous contraction can be elicited in dogs with regional LV denervation as a result of an early and enhanced contraction in the innervated region during neural sympathetic activation. The reverse was observed with systemic administration of norepinephrine because of catecholamine supersensitivity in the denervated posterior wall.
Reabsorption kinetics of albumin from pleural space of dogs
Authors: Miniati M. , Parker J. C. , Pistolesi M. , Cartledge J. T. , Martin D. J. , Giuntini C. , Taylor A. E.
Published: December 2017

The reabsorption of albumin from the pleural space was measured in eight dogs receiving 0.5 ml intrapleural injection of 131I-labeled albumin and a simultaneous intravenous injection of 125I-labeled albumin. Plasma curves for both tracers were obtained over 24 h. The 125I-albumin curve served as input function of albumin for interstitial spaces, including pleura, whereas the 131I-albumin curve represented the output function from pleural space. The frequency function of albumin transit times from pleural space to plasma was obtained by deconvolution of input-output plasma curves. Plasma recovery of 131I-albumin was complete by 24 h, and the mean transit time from pleura to plasma averaged 7.95 +/- 1.57 (SD) h. Albumin reabsorption occurred mainly via lymphatics as indicated by experiments in 16 additional dogs in which their right lymph ducts or thoracic ducts were ligated before intrapleural injection. A pleural lymph flow of 0.020 +/- 0.003 (SD) ml.kg-1.h-1 was estimated, which is balanced by a comparable filtration of fluid into the pleural space. This suggests that, under physiological conditions, the subpleural lymphatics represent an important control mechanism of pleural liquid pressure.
Role of calcium and protein kinase C in ANP secretion by cultured rat cardiocytes
Authors: Matsubara H. , Hirata Y. , Yoshimi H. , Takata S. , Takagi Y. , Umeda Y. , Yamane Y. , Inada M.
Published: December 2017

The secretory mechanism of rat atrial natriuretic peptide (rANP) was studied in vitro with the use of primary culture of atrial myocytes from neonatal rats. Norepinephrine, phenylephrine, and carbamylcholine stimulated immunoreactive (IR) rANP secretion, whereas neither angiotensin II, arginine vasopressin, nor isoproterenol affected its secretion. The stimulatory effects of carbamylcholine and phenylephrine were blocked by atropine and prazosin, respectively. 12-O-tetradecanoylphorbol-beta-acetate (TPA), protein kinase C activator, induced a dose-dependent increase in IR rANP secretion, and TPA combined with Ca2+ ionophore ionomycin produced a synergistic effect. Ca2+-channel agonist BAY K 8644 also stimulated IR rANP secretion, the effect of which was blocked by Ca2+-channel antagonist nifedipine. These data suggest that alpha 1-adrenergic and muscarinic cholinergic agonists have direct action on rat cardiocytes to stimulate ANP secretion that involves receptor-mediated mobilization of intracellular Ca2+ and activation of protein kinase C.
Adrenergic and histaminergic neural interactions in dog paws
Authors: Baker C. H. , Davis D. L. , Sutton E. T. , Lindsey B. G.
Published: December 2017

The mechanisms underlying the vascular responses of superficial fibular nerve stimulation (SFNS) have not been defined. Right hindpaws of anesthetized heparinized dogs were vascularly and neurally isolated, enclosed in a volume recorder, and perfused with controlled pressure. Vascular volume (VV) (131I-labeled albumin) and rate of tissue volume changes (VT) (plethysmography) were determined. SFNS increased blood flow resistance, reduced capillary filtration coefficient (CFC) and permeability-surface area product (PS) of 86Rb, increased VV, and reduced 131I-albumin recovery. VT increased at the rate of 3.35 +/- 0.45 ml/min. SFNS during terbutaline increased resistance, CFC, PS, and VV were unchanged, 131I-albumin recovery was complete, and VT increased at one-fourth the control rate. Phentolamine and yohimbine blocked all responses to SFNS. Prazosin with SFNS attenuated hemodynamic changes and VT increased to two-thirds of control, decreased VV, albumin, and Rb recovery but not PS and CFC. SFNS during pyrilamine maleate reduced VT increase to two-thirds of control rate and blocked decreases in PS and CFC. Metiamide did not change the SFNS responses, except to reduce vascular volume and VT. The combined histamine H1 and H2 blockers reduced VT increase to one-third of control and attenuated albumin loss, prevented histamine dilation, attenuated vasopressin and norepinephrine but not angiotensin constriction. SFNS stimulation increased precapillary resistance by alpha 1- and alpha 2-receptors and venous resistance by alpha 2-receptors and increased permeability by histamine release from endothelium.
Pulmonary vascular response to platelet-activating factor in conscious sheep
Authors: Toyofuku T. , Kobayashi T. , Koyama S. , Kusama S.
Published: December 2017

Hemodynamic response to an intravenous infusion of platelet-activating factor (PAF; 1 microgram/kg) was studied in conscious sheep with lung lymph fistulas. PAF induced increases in pulmonary arterial pressure and decreases in left atrial and systemic arterial pressures and in cardiac output, together with transient increases in thromboxane (Tx) A2 (as TxB2) and prostacyclin (as 6-keto-PGF1 alpha) values in plasma and lung lymph. There were also transient decreases in circulating leukocytes and platelets. The second infusion of PAF induced a reduced response compared with the first one, but the response to PAF was afterward maintained. Pretreatment with OKY 046, a thromboxane synthase inhibitor, reduced the first pulmonary vasoconstriction in response to PAF to a degree equivalent to that after successive infusions of PAF in control sheep. Pulmonary response to PAF (except on first infusion) and systemic cardiovascular response did not change whether or not TxA2 was produced. We therefore concluded that PAF mediates pulmonary and systemic cardiovascular effects via mechanisms other than TxA2 during successive infusions of PAF and that PAF-induced TxA2 contributes only to the pulmonary response to PAF on first infusion of the latter.
Myocardial sarcolemma in ischemia: a quantitative freeze-fracture study
Authors: Frank J. S. , Beydler S. , Wheeler N. , Shine K. I.
Published: December 2017

Freeze-fracture electron microscopy permits the visualization of the intramembrane particles (IMP). These IMPs are presumably proteins responsible for the main functions of the membrane. Quantitative techniques (Clark-Evan statistics) were applied to determine in a critical manner whether IMP pattern shifts (random, clustered, or ordered) occur under the ischemic conditions (5-45 min with and without reperfusion) and whether this change is related to the experimental condition. In each case three hearts, eight replicas/heart, one area of 0.25 micron 2 of membrane fracture face/replica was measured to give a total of 6 micron 2 of membrane counted for each condition (control vs. ischemic). A mixed effects nested model analysis of variance was performed in each variable. We found that IMP aggregation can be present in some control membranes, but the degree of aggregation was greater and more consistent in membranes made ischemic and followed by reperfusion. Most striking was the significant clustering of IMPs in membranes from hearts ischemic for only 5 min. Reperfusion after only 5 min of ischemia reversed IMP clustering. Functionally at this time there is an increase in K+ concentration in the interstitial space that reaches approximately 15 mM within 10 min and reverses on reperfusion. The structural alteration in IMPs appears to parallel the function in ischemic hearts.
Constriction of lymphatics by catecholamines, carotid occlusion, or hemorrhage
Authors: Dabney J. M. , Buehn M. J. , Dobbins D. E.
Published: December 2017

Regulation of lymphatics by sympathetic nerves or hormones seems probable. To elucidate this, we perfused a lymphatic vessel in the paw of the anesthetized dog while measuring lymphatic perfusion pressure. We studied the effects of norepinephrine, epinephrine, hemorrhage, and carotid occlusion on lymphatic pressure. Blood was pumped to the forelimb via the brachial artery. Cannulas were placed to measure systemic, central venous, and forelimb vascular pressures. Catecholamines, whether added to the lymphatic perfusate or infused into the forelimb arterial blood, and bilateral carotid occlusion significantly increased lymphatic perfusion pressure. Perfusion of prenodal lymphatics disconnected from downstream vessels and nodes indicated that this increase occurred primarily in prenodal lymph vessels. Hemorrhagic hypotension to 55 mmHg did not affect lymphatic pressure but reduction to 35 mmHg did. The increase in lymphatic pressure produced by epinephrine and norepinephrine was blocked by phentolamine. Increased lymphatic perfusion pressure subsequent to exogenous catecholamines, severe hemorrhagic hypotension, or bilateral carotid occlusion supports the possibility that lymphatic function is modulated by adrenergic mechanisms in physiological and/or pathophysiological states.
Increased angiotensin II receptors in brain nuclei of DOCA-salt hypertensive rats
Authors: Gutkind J. S. , Kurihara M. , Saavedra J. M.
Published: December 2017

We analyzed angiotensin II (ANG II) receptors by in vitro autoradiography in selective brain nuclei of control, salt-treated (1% NaCl in drinking water), deoxycorticosterone acetate (DOCA)-treated (DOCA pivalate, 25 mg/kg sc weekly), and DOCA-salt-treated (DOCA + salt treatments) uninephrectomized male Wistar-Kyoto rats. After 4 wk of treatment, only the DOCA-salt group developed hypertension. ANG II binding increased in median preoptic nucleus and subfornical organ of salt- and DOCA-treated rats. DOCA-treated rats also showed increased ANG II binding in paraventricular nucleus. DOCA-salt-treated rats showed higher ANG II binding in nucleus of the solitary tract and area postrema, as well as in the areas mentioned before. Although salt and/or DOCA treatments alone increased ANG II receptors in some brain nuclei, after combined DOCA-salt treatment there was significantly higher ANG II binding in all areas, except the median preoptic nucleus. These results suggest that increased ANG II receptors in selected brain areas may play a role in the pathophysiology of mineralocorticoid-salt experimental hypertension.
Pulsatile sinus pressure changes evoke sustained baroreflex responses in awake dogs
Authors: Mendelowitz D. , Scher A. M.
Published: December 2017

A modified Stephenson-Donald preparation was used to control pressure in an isolated carotid sinus in conscious dogs with all other arterial baroreceptors denervated. Sinus pressure was changed from preisolation control levels to either an elevated static or an elevated pulsatile pressure for 5 min. These sinus pressure changes evoked similar initial decreases in arterial pressure. The elevated static sinus pressure (150 or 175 mmHg) caused an initial depressor response of -32.7 +/- 5.5 mmHg, which then decayed rapidly. Five minutes after the change in sinus pressure, the depressor response was abolished, as arterial pressure returned to control pressure. This decay of the response would be expected if resetting occurred. In contrast, when the sinus was exposed to elevated pulsatile pressures (125 or 150 mmHg mean, 50 mmHg pulse pressure) depressor responses were sustained throughout the sinus pressure change (-23.2 +/- 5.3 mmHg initial, -29.0 +/- 4.8 mmHg at 5 min; P greater than 0.4). These results demonstrate that while the reflex responses rapidly reset to elevated static sinus pressures, elevated pulsatile pressures elicit sustained reflex responses.
Lipoxygenase inhibitors block O2 responses of hamster cheek pouch arterioles
Authors: Jackson W. F.
Published: December 2017

The hypothesis that a lipoxygenase is involved in arteriolar oxygen reactivity was tested in the superfused hamster cheek pouch preparation by assessment of the effects of three lipoxygenase inhibitors on the response of arterioles to changes in superfusate PO2. Superfusion of hamster cheek pouches with nordihydroguaiaretic acid (NDGA), 5,8,11,14-eicosatetraynoic acid (20 microM ETYA), or 100 microM 1-phenyl-3-pyrazolidone (phenidone) decreased (10 microM NDGA) or eliminated (30 microM NDGA, ETYA, or phenidone) the constriction of arterioles induced by elevation of superfusate oxygen tension. The response of the arterioles to the alpha 1-adrenergic agonist phenylephrine was not significantly affected by these inhibitors, an indication that the decreased oxygen response was not due to a nonspecific decrease in arteriolar reactivity. These data suggest that arteriolar oxygen reactivity in the hamster cheek pouch might involve a lipoxygenase or other noncyclooxygenase oxygen-dependent biochemical pathway that can be inhibited by NDGA, ETYA, and phenidone.
Endothelium-dependent pressure-induced contraction of isolated canine carotid arteries
Authors: Rubanyi G. M.
Published: December 2017

Experiments were conducted in a bioassay system, where a canine coronary artery ring without endothelium (bioassay tissue) was superfused by the effluent from a perfused canine carotid artery segment with endothelium (donor segment). A rapid increase in transmural pressure (from near 0 to 32-38 mmHg) triggered active contraction of the donor segment and simultaneously of the bioassay tissue. These contractions were prevented by removal of the endothelium from the donor segment but not by treatment of the segment with indomethacin. Exposure to elevated pressure depressed basal, acetylcholine-, and flow-induced release of endothelium-derived relaxing factor(s). Methylene blue prevented the pressure-induced contraction of the bioassay ring. These data show that pressure-induced contraction of isolated carotid arteries is endothelium dependent and is mediated by the depression of the synthesis and/or release of endothelium-derived relaxing factor(s).
Regional hemodynamic responses to adrenoceptor antagonism in conscious rats
Authors: Gardiner S. M. , Bennett T.
Published: December 2017

Changes in blood pressure and renal, mesenteric, and hindquarters vascular resistances were measured in conscious Long-Evans and Brattleboro (vasopressin-deficient) rats in response to sequential, continuous administrations of prazosin and idazoxan in the absence or presence of ICI 118551 (beta 2-adrenoceptor antagonist) or propranolol. The large transient hypotensions elicited by prazosin and, subsequently, by idazoxan were associated with renal and hindquarters vasodilatations in both strains of rat. In Brattleboro rats, prazosin also elicited mesenteric vasodilatation. Pretreatment with ICI 118551 reduced the initial hypotensive effects and hindquarters vasodilatations elicited by prazosin and idazoxan, but the hemodynamic effects of prazosin were not significantly affected by propranolol. These results are consistent with propranolol antagonizing beta 1-adrenoceptor-mediated effects on the heart and the renin-angiotensin system that act to offset a beta 2-adrenoceptor-mediated vasodilatation, which contributes to the effects elicited by alpha-adrenoceptor antagonism. Hemodynamic responses to captopril and d(CH2)5DAVP (in Long-Evans rats) in the presence of adrenoceptor antagonists were consistent with a major cardiovascular role of the renin-angiotensin system and a less overt role of vasopressin until the latter system was blocked.
Relationship between dog saphenous vein reactivity and Na content
Authors: Berczi V. , Simon G.
Published: December 2017

The physiological significance of the wide range of spontaneous variation in the total Na content of the dog saphenous vein (SV) was investigated. The SV of pentobarbital-anesthetized male mongrel dogs was perfused in vitro with the dogs' own venous blood, and its reactivity to acetylcholine (ACh) and norepinephrine (NE) was measured. The contralateral SV was removed for measurements of total and intracellular (Li exchange at 4 degrees C) Na and K content, DNA content, and muscle width. Reactivity to ACh correlated directly with total and extracellular SV Na content, and reactivity to NE correlated directly with total and intracellular K content. Reactivity to NE was unrelated to ACh reactivity, plasma NE concentration, or venous wall DNA content or muscle width. ACh-mediated venoconstriction was approximately 10 times more sensitive to inhibition by amiloride, an inhibitor of Na-entry pathways, than NE-mediated venoconstriction. The finding that extracellular Na content is a marker of reactivity to ACh is compatible with experimental evidence that the mode of action of ACh may be the stimulation of Na influx. The positive correlation between the K content and reactivity of veins to NE suggests that there is a link between intracellular K content and the release of Ca from the sarcoplasmic reticulum in response to NE.
Responses of cerebral arteries after ischemia and reperfusion in cats
Authors: Mayhan W. G. , Amundsen S. M. , Faraci F. M. , Heistad D. D.
Published: December 2017

Our goal was to determine whether responses of cerebral arteries are altered after cerebral ischemia and reperfusion. We measured diameter of cerebral arteries (150-180 micron) in cats in response to topical application of acetylcholine (ACh) and serotonin, which release endothelium-derived relaxing factor (EDRF), and adenosine and angiotensin, which do not release EDRF. Diameter of arteries was measured before and after 10 or 30 min of cerebral ischemia, when base-line diameter had returned to control levels. Under control conditions, serotonin and angiotensin constricted cerebral arteries by 16 +/- 2 and 23 +/- 3% (means +/- SE), respectively, and ACh and adenosine dilated cerebral arteries by 22 +/- 2 and 23 +/- 3%, respectively. During reperfusion after 10 min of cerebral ischemia, constrictor responses of cerebral arteries were preserved. Vasodilator responses of arteries to ACh after 10 min of ischemia were heterogeneous. In 6 of 15 cats, vasodilatation in response to ACh was preserved. In contrast, in 9 of 15 cats, vasodilatation in response to ACh was impaired (7 +/- 3%). In both groups, vasodilatation in response to adenosine was not impaired after 10 min of ischemia. During reperfusion after 30 min of cerebral ischemia, constrictor responses of cerebral arteries were preserved. In contrast, dilatation of cerebral arteries in response to ACh and adenosine was impaired. We speculate that impaired cerebral vasodilatation after ischemia, with maintenance of vasoconstriction, may contribute to impaired reperfusion after cerebral ischemia.
Epicardial activation after unsuccessful defibrillation shocks in dogs
Authors: Shibata N. , Chen P. S. , Dixon E. G. , Wolf P. D. , Danieley N. D. , Smith W. M. , Ideker R. E.
Published: December 2017

To study defibrillation, shocks were given to seven dogs during electrically induced fibrillation, while recordings were made from 56 epicardial electrodes. Shocks were given via electrodes on the left ventricular apex and the right atrium, creating an uneven shock field with much higher potential gradients in the apex than in the base of the ventricles. For unsuccessful 0.01- to 0.05-J shocks, activation occurred soon after the shock at many sites in both the base and the apex. For 0.1- to 0.5-J shocks, the number of early activation sites was greatly decreased, and the latency from the shock until earliest recorded activation was greatly increased at the apex but not at the base. For 1- to 5-J shocks, one to three early sites were present and confined to the base, with a long latency between the shock and the appearance of these early sites. The latency and location of earliest activation were similar to those after 1- to 5-J shocks given to induce fibrillation during normal paced rhythm. Shocks of 10 J successfully defibrillated. These findings suggest that the shock field can have at least three effects. One, a weak field fails to halt the activation fronts of fibrillation. Two, a stronger field halts but then reinduces fibrillation in a manner similar to that of the same strength field during the vulnerable period of normal rhythm. Three, a still higher field halts fibrillation without reinitiating it. Successful defibrillation requires a shock strong enough to create this third field intensity throughout the ventricles.
Sympathetic tone affects human limb vascular resistance during a maximal metabolic stimulus
Authors: Sinoway L. I. , Wilson J. S. , Zelis R. , Shenberger J. , McLaughlin D. P. , Morris D. L. , Day F. P.
Published: December 2017

To evaluate the relationship between heightened sympathetic tone and maximal metabolic vasodilation, peak forearm blood flow (ml.min-1.100 ml-1) was measured plethysmographically in 18 volunteers after the release of 10 min of arterial occlusion (the peak reactive hyperemic blood flow response, RHBF) both before and after a stimulus to induce heightened sympathetic tone. The stimulus was the application of ice to the forehead for 90 s just before and during RHBF measurements. Mean arterial cuff blood pressure (MAP; mmHg) was calculated, and corresponding resistance (R; mmHg.ml-1.min.100 ml) was derived from blood pressure divided by RHBF. During ice application, blood pressure rose (pre 92 vs. post 115 ml/mmHg; P less than 0.05), peak RHBF was unchanged (pre 38.8 vs. post 36.4 ml.min-1.100 ml-1; not significant), but R during the maximal metabolic stimulus rose (pre 2.5 vs. post 3.2 mmHg.ml-1.min.100 ml; P less than 0.05). To examine the effects of heightened sympathetic tone on conduit vessels, simultaneous measurements of maximal metabolic blood flow (RHBF) and brachial artery Doppler velocity (V, cm/s) were conducted (n = 5) with and without ice applied to the forehead. Velocity rose by 70% as flow remained constant. Thus brachial artery area (area = flow/velocity) and diameter decreased substantially (20% decrease in diameter). The increase in R noted with ice was due to an alpha-mediated response, since the increase in R was blocked by oral prazosin (n = 6) and was unaffected by maneuvers to alter myogenic tone (n = 5). We conclude that maximal metabolic vasodilation can be counteracted to some extent by the effects of heightened sympathetic tone. Moreover, some of the interaction between these two opposing influences takes place at the arterial level.
Positive inotropic action of novel vasoconstrictor peptide endothelin on guinea pig atria
Authors: Ishikawa T. , Yanagisawa M. , Kimura S. , Goto K. , Masaki T.
Published: December 2017

Endothelin (ET), a novel 21-amino acid peptide isolated from the culture supernatant of porcine aortic endothelial cells, has been shown to be the most potent of all known vasoconstrictor substances. The purpose of the present study was to investigate the effects and the mode of actions of ET on the heart. ET exerted a positive inotropic effect in a dose-dependent manner on the electrically driven left atria of guinea pigs. The ET-induced response was of slow onset and characteristically long lasting. The half-maximal effective dose of the ET-induced response was about 1 nM, indicating that ET is one of the most potent cardiotonic substances. The response was presumably caused through direct actions of ET on the myocytes, since adrenergic, histaminergic, and serotonergic antagonists showed no effect on the response. The dose-response relationship of ET for the positive inotropic effect was displaced to the right in a parallel fashion by 0.3 microM nicardipine. In the left atria depolarized with 22 mM KCl, ET produced gradually increasing contractions in conjunction with the slow response action potentials in response to the electrical pacing. These results suggest that the ET-induced response on the left atria is intimately related to the influx of extracellular Ca2+.
A new oil-gate concentration jump technique applied to inside-out patch-clamp recording
Authors: Qin D. Y. , Noma A.
Published: December 2017

A new method was developed to instantaneously replace the solution on the inner side of an inside-out membrane patch in order to measure time courses with which active substances acted on single ionic channels. Inside-out membrane patches were isolated from single ventricular cells of the guinea pig heart. The recording bath consisted of two chambers separated by a partition having a narrow slit. Mixing of two test solutions through this slit was prevented by filling it with paraffin oil. The pipette tip with a tightly sealed inside-out membrane patch was moved through the oil from one solution to the other so that the pipette tip was instantaneously exposed to a new solution. When the pipette tip was jumped between different K+ concentrations, the leak current through the membrane patch increased or decreased with a half time of 6.3 +/- 3.0 ms (n = 15). The amplitude of single K+ channel currents changed to a new steady level within approximately 20 ms. These time courses were well explained by diffusion of K+ in the dead space between the pipette tip opening and the membrane patch. An application of this method to the ATP-regulated K+ channel revealed a latent period of 1-2 s before the channel started its activity after the instantaneous removal of ATP, whereas no obvious latency was observed in the rapid suppression of the channel, which was completed in 100-300 ms after reapplying ATP.
Inhibitors of cyclooxygenase augment serotonergic responsiveness in canine coronary arteries
Authors: Blaise G. , Iqbal A. , Vanhoutte P. M.
Published: December 2017

Experiments were designed to determine the role of products of cyclooxygenase in contractions of coronary smooth muscle evoked by serotonin. Rings of canine coronary artery without endothelium were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution. Serotonin caused concentration-dependent contractions followed by secondary relaxations at higher doses. Indomethacin and meclofenamate augmented both the contraction and the relaxation. Indomethacin did not affect contractions evoked by increasing concentrations of either phenylephrine, prostaglandin F2 alpha, or potassium chloride. Propranolol did not affect the concentration-response curve to serotonin under control conditions; it prevented the facilitated contraction to the monoamine but not the augmented secondary relaxation caused by the inhibitors of cyclooxygenase. These results suggest that endogenous prostanoids simultaneously inhibit the contractile process and brake relaxations induced by higher concentrations of serotonin. As a consequence, inhibitors of prostanoid formation facilitate the vasospastic component of the response to the monoamine in large coronary arteries. For unknown reasons, propranolol prevents this facilitation.
An approach to measuring cardiac output with Doppler flow probes in conscious rats
Authors: Veelken R. , Schelling P. , Unger T.
Published: December 2017

The continuous measurement of cardiac output in conscious rats is difficult. Previously, Doppler flow probes have been applied to the ascending aorta by means of silicone cuffs. The placement of these cuffs can conceivably introduce errors engendered by the destruction of nerve fibers that are important in cardiac autonomic innervation. We report a novel method of Doppler flow-probe attachment directly to the ascending aorta by means of a polyacrylic cement. When we compared the response with baroreceptor activation with methoxamine and nitroprusside in conscious rats equipped either with probes attached via cuffs or directly via cement, we observed that animals equipped with cuffs failed to give the expected cardiac output and heart rate responses after nitroprusside administration. In contrast, animals that had their probes attached with cement displayed the expected responses. The data not only show that probes applied with cement give a result superior to probes attached with cuffs but also verify the suspicion that the ascending aorta is associated with nerve fibers that are important in mediating baroreceptor responses.
V1 vs. combined V1+V2 vasopressin blockade after hemorrhage in conscious dogs
Authors: Liard J. F.
Published: December 2017

We examined the hypothesis that V2-like receptors might contribute to the hemodynamic response seen after blockade of the vasoconstrictor (V1) effect of arginine vasopressin (AVP) in nonhypotensive hemorrhage. Seven chronically instrumented dogs were bled 15 ml/kg within 15 min on two different days, at least 3 days apart, and then injected either with the V1 antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)2-(O-methyl)tyrosine]AVP [d(CH2)5Tyr(Me)AVP, 10 micrograms/kg] or with the combined V1+V2 antagonist [1(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)2-(O-ethyl)-D-tyrosine)4-valine]AVP [d(CH2)5-D-Tyr-(Et)VAVP (10 micrograms/kg)]. Mean arterial pressure, heart rate, and cardiac output (electromagnetic flowmeter) were measured before as well as after hemorrhage and for 10 min after antagonist administration. Both antagonists given after hemorrhage significantly decreased mean arterial pressure as well as total peripheral resistance and increased cardiac output. The V1 antagonist also increased heart rate significantly. No significant hemodynamic changes were measured in another group of six dogs in the absence of antagonist treatment. Although hemodynamic changes tended to be greater with the V1 antagonist than with the combined V1+V2 antagonist, a significant difference between the two analogues was established only for heart rate. These results indicate that in hemorrhage interaction with V2-like receptors plays only a modest role in the hemodynamic changes after V1 blockade in conscious dogs, contrary to what was found in dehydration.
Reentrant and focal arrhythmias in low potassium in isolated rabbit atrium
Authors: Lammers W. J. , Allessie M. A. , Bonke F. I.
Published: December 2017

In isolated superfused left atria of the rabbit, tachyarrhythmias became highly inducible with a decrease of the extracellular potassium concentration to 2.0 mM. The nature of the arrhythmias was determined with a high-resolution mapping system. In several cases, abnormal impulse formation was found, but the majority of arrhythmias (75%) was caused by a circus movement of the impulse. Furthermore, circus-movement tachyarrhythmias often degenerated into fibrillatory activity, and activation maps revealed the presence of multiple wavelets during this chaotic rhythm. The occurrence of reentrant arrhythmias may be caused either by an increase in inhomogeneity in conduction or by a shortening of the wavelength in low potassium. Inhomogeneity in conduction was determined by calculating the difference in activation times between neighboring electrodes. In low potassium, premature activation significantly increased the inhomogeneity index compared with slow rhythm (from 2.2 to 3.9; P less than 0.001) but was not significantly different from the inhomogeneity measured at normal potassium concentrations. Low potassium, however, did shorten significantly the wavelength of the impulse by approximately 40%. The increased inducibility of reentry in low potassium is therefore caused by a reduction of the length of the excitation wave and not by an increase in inhomogeneity in conduction.
Pulmonary and peripheral lymph protein clearance during bacteremia after surgery
Authors: Charash W. E. , Saba T. M. , Lewis E. P. , Lewis M. A.
Published: December 2017

An increase in pulmonary transvascular protein clearance is seen in sheep following postoperative bacteremia. We evaluated whether this increased protein clearance is specific for the lung by comparing in sheep the effect of postoperative bacteremia on both pulmonary and prefemoral lymph protein clearance. Fibronectin, implicated as a factor influencing vascular permeability, was also measured. After intravenous infusion of a sublethal dose of 5 x 10(8) live Pseudomonas aeruginosa (n = 10), pulmonary lymph flow (QL) increased 146% (P less than 0.01), and the lung lymph-to-plasma (L/P) total protein concentration ratio increased 21% (P less than 0.05). This resulted in a 208% elevation (P less than 0.01) in lung protein clearance (LPC = QL x L/P). In contrast, peripheral lymph flow and peripheral protein clearance were not altered. After intravenous infusion of a lethal dose of 5 x 10(9) live Pseudomonas (n = 7), QL rose 243–348% (P less than 0.025), whereas the lung L/P remained at base line, resulting in a 240-358% increase in LPC (P less than 0.025). Again, peripheral lymph flow and protein clearance did not increase. Plasma fibronectin declined slightly after low-dose bacterial challenge but decreased (P less than 0.001) 40% by 4–5 h after high-dose bacterial challenge. After both low- and high-dose bacterial challenge, fibronectin in pulmonary lymph increased (P less than 0.05) relative to total protein. In contrast, no change in peripheral lymph fibronectin was seen. Thus, while postoperative bacteremia increased lung protein clearance, it did not increase peripheral protein clearance, suggesting specificity with regard to the microvascular response to bacteremia.
Blood flow in normal and denervated muscle during exercise in conscious rats
Authors: Delp M. D. , Armstrong R. B.
Published: December 2017

The purpose of this study was to test the hypothesis that extrinsic mechanical factors, i.e., the dynamic shortening and lengthening imposed on a muscle during limb movements and the rhythmic compressions as surrounding muscles contract and relax, contribute to the initial muscle hyperemia during locomotion in conscious male Sprague-Dawley rats. Soleus and lateral head of gastrocnemius muscles were surgically denervated in one hindlimb several hours before exercise to remove 1) local metabolic vasodilator effects, 2) vasoconstrictor or vasodilatory influences mediated through sympathetic postganglionic fibers, and 3) intrinsic mechanical pumping. Blood flow was measured with radioactive microspheres during preexercise and at 30 s and 5 min of exercise in rats walking at 15 m/min or a motor-driven treadmill. Glycogen concentrations were also measured as an indicator of muscular activity to verify the denervation. Blood flows to control muscles in the normal limb were similar to previously reported values during preexercise and exercise. Denervation, however, decreased preexercise blood flow (69–88%) to muscle composed predominantly of oxidative fibers and increased flow (53%) to muscle composed predominantly of glycolytic fibers. During exercise, blood flow to denervated muscles either remained unchanged or decreased. These data suggest that extrinsic mechanical factors do not significantly contribute to the initial hyperemic response at the onset of low-intensity exercise in normal muscle.
Effect of jugular venous pressure on cerebral autoregulation in dogs
Authors: McPherson R. W. , Koehler R. C. , Traystman R. J.
Published: December 2017

We determined the importance of a myogenic sensor of cerebral autoregulation by assessing the effect of vascular transmural pressure on cerebral blood flow (CBF) as cerebral perfusion pressure (CPP) was decreased. Decreasing CPP by decreased arterial pressure (Pa) or increased intracranial pressure (Pcsf) decreases transmural pressure, whereas increased jugular venous pressure (Pjv) increases transmural pressure. Regional CBF was measured in barbiturate-anesthetized dogs using radiolabeled microspheres. In group 1 (n = 5), CPP was decreased by decreasing Pa; in group 2 (n = 5), CPP was decreased by increasing Pcsf (Pa = 80 mmHg); and in group 3 (n = 5) CPP was decreased by increasing Pjv (Pa = 80 mmHg). CPP was reduced from 80 to 30 mmHg in 10-mm increments in each group. In groups 1 and 2 regional CBF was maintained as CPP was decreased to 40 mmHg; however, at CPP of 30 mmHg, blood flow to cerebrum, caudate, and periventricular white matter decreased, whereas flow to cerebellum and medulla remained unchanged. In group 3 regional CBF was unchanged as CPP decreased from 80 to 50 mmHg but decreased in all regions as CPP decreased further. In all three groups, cerebrovascular resistance continuously declined as CPP was decreased. In all groups, cerebral O2 uptake was unaltered. Autoregulation fails at a higher CPP with increased Pjv than with decreased Pa or increased Pcsf, particularly in brain stem. We conclude that metabolic autoregulation predominates over the myogenic mechanism until CPP is low.
Intrarenal blood flow distribution in dog kidney determined by 99mTc microaggregates and 201Tl
Authors: Abildgaard U. , Amtorp O. , Gyring J. , Daugaard G. , Larsen B.
Published: December 2017

Intrarenal distribution of blood flow was assessed with radioactive albumin microaggregates (MA) in three cortical zones of the dog kidney. The experimentally obtained zonal fractions of total renal blood flow were compared with predicted zonal blood flow fractions obtained in a mathematical model. The maximal degree of skimming that could possibly occur in a single experiment was estimated. The analysis showed that local blood flow in the inner cortical zone was maximally underestimated by 17% because of skimming of MA, and in the outer cortical zone the blood flow was maximally overestimated by 13% with the method of radioactive MA uptake. Renal uptake of 201Tl was measured simultaneously in exactly the same locations. Paired measurements of intrarenal blood flow distribution by MA and Tl uptake methodologies showed that local blood flow assessed with MA in the inner cortical zone was significantly lower than that obtained with 201Tl and that a higher blood flow rate was obtained in the outer cortical zone with MA compared with 201Tl. This disparity could be accounted for by the effect of skimming of MA as predicted by the model.
Effects of hemodilution on gastric and intestinal oxygenation
Authors: Kiel J. W. , Riedel G. L. , Shepherd A. P.
Published: December 2017

To determine the effects of hemodilution on gastric and intestinal oxygenation, isolated segments of canine stomach and small bowel were perfused by a pressurized reservoir with blood at hematocrits of 40 and 20%. Arteriovenous O2 difference, blood flow, and arterial and venous pressures were monitored continuously as perfusion pressure was reduced in 30-mmHg steps from 180 to 30 mmHg. O2 consumption was calculated as the product of the steady-state arteriovenous O2 difference and blood flow at each perfusion pressure. Gastric and intestinal O2 uptake were relatively well maintained over most of the pressure range when the hematocrit was set at 40%. After hemodilution, gastric O2 uptake decreased significantly only at 90 and 60 mmHg, but intestinal O2 uptake was significantly reduced except at 30 mmHg. When gastric and intestinal O2 uptake were plotted as a function of blood flow, the O2 uptake vs. blood flow relationship were shifted down and to the right by hemodilution. Hemodilution also linearized the O2 uptake vs. blood flow relationship in the intestine. However, when O2 uptake was plotted as function of O2 delivery, the gastric O2 uptake vs. delivery curves at the two hematocrits were superimposed on each other, but the O2 uptake vs. delivery curves for the intestine diverged except at low rates of O2 delivery. We conclude that by reducing the O2-carrying capacity of the blood, hemodilution adversely affects gastric and intestinal oxygenation. Our results also indicate that hemodilution lowers gastric O2 uptake by reducing O2 delivery; however, hemodilution lowers intestinal O2 uptake not only by reducing O2 delivery but also by impairing O2 extraction.
Filtration coefficient in cat hindlimb using protein concentration changes
Authors: Watson P. D. , Wolf M. B.
Published: December 2017

The maximum value of capillary filtration coefficient (CFC) in maximally vasodilated cat skeletal muscle is disputed. It was hypothesized that the wide range of reported values was caused by the inability of gravimetric and volumetric measurements of tissue volume to separate transcapillary filtration from vascular volume changes. Consequently, we developed a method of measuring filtration rates from changes in venous protein concentration using Evan's blue-labeled albumin in the isolated hindlimb (pentobarbital sodium anesthesia). The filtration coefficient (PFFC) calculated from these filtration rates after a step in venous pressure should not be influenced by vascular volume changes. When the perfusate flow rate through the hindlimb was greater than 15 ml.min-1.100 g muscle-1, PFFC was 0.0085 +/- 0.0015 (SD, n = 8) ml.min-1.mmHg-1.100 g muscle-1. PFFC was observed to be unvarying from 1 to 12 min after the venous pressure elevation, in contrast to CFC values, which fall during the same period. It is argued that the difference between CFC and PFFC values is caused by vascular volume changes.
Circulatory effects of PAF-acether in newborn piglets
Authors: Bradley L. M. , Goldstein R. E. , Feuerstein G. , Czaja J. F.
Published: December 2017

Platelet-activating factor (PAF-acether) is a lipid mediator that can exhibit potent vasoconstrictor influence in the pulmonary vessels. Therefore, the release of PAF-acether during inflammatory conditions in newborns might cause deleterious increases in pulmonary vascular tone. Thirty-four anesthetized open-chest newborn piglets were given 0.01-1 nmol PAF-acether iv. In separate experiments, animals were untreated or treated with either indomethacin (a cyclooxygenase inhibitor), SQ 29548 (a thromboxane receptor blocker), or LY 171883 (a leukotriene receptor blocker). The primary hemodynamic change was a 67 to 1,537% increase in the pulmonary vascular resistance index (PVRI) (P less than 0.01): mean pulmonary artery pressure (PAP) rose significantly at all doses tested, whereas only the largest dose consistently decreased cardiac index. Treatment with indomethacin or SQ 29548 prevented the decrease in cardiac index and attenuated the PAF-acether-induced rises in PAP and PVRI. Vehicle and LY 171883 had no effect. The inhibitory influence of indomethacin and SQ 29548 suggests that an important component of PAF-acether's pulmonary vasoconstrictor action is mediated (at least in the newborn piglet) by cyclooxygenase products, most likely thromboxane.
Influence of nonuniformity on rate of left ventricular pressure fall in the dog
Authors: Lew W. Y. , Rasmussen C. M.
Published: December 2017

We examined the influence of nonuniformity in regional ventricular function on the rate of left ventricular pressure fall in 10 anesthetized dogs. Ultrasonic segment gauges were implanted in the midwall of the anterior, lateral, and posterior left ventricle. In seven dogs, nonuniformity was produced by infusing isoproterenol (0.4 microgram/ml) into the mid-left anterior descending coronary artery at low flow (0.5 +/- 0.7 ml/min) and high flow (1.5 +/- 1.2 ml/min) rates, for total doses of 0.1 +/- 0.1 and 0.3 +/- 0.2 micrograms, respectively. This produced a dose-dependent increase in anterior segment shortening so that shortening was completed earlier and marked segment lengthening occurred during isovolumic relaxation. Lateral and posterior segments were not directly stimulated. The heart rate, left ventricular end-diastolic pressure, and peak systolic pressure remained constant. However, tau, the time constant of left ventricular pressure fall, increased from 32 +/- 8 to 37 +/- 10 ms with the low dose, and from 35 +/- 6 to 49 +/- 12 ms with the high dose of isoproterenol. Similar results occurred in two dogs when isoproterenol was infused into the proximal, mid, or distal left anterior descending and in three dogs with infusions in the left circumflex coronary artery. We conclude that nonuniformity of regional left ventricular function is an important and independent factor regulating the rate of pressure fall in the intact ejecting left ventricle.
Effects of steps in cardiac output and arterial pressure in awake dogs with AV block
Authors: O'Leary D. S. , Scher A. M. , Bassett J. E.
Published: December 2017

In awake dogs with atrioventricular block, we examined the responses in total peripheral resistance and atrial rate to square-wave changes in mean arterial pressure or cardiac output. We compared the responses 2-3 min after a step change with the responses 19-20 min after a step. With resetting of arterial pressure control, the compensatory responses should decrease as the baroreceptors reset to the prevailing pressure. With step changes in mean arterial pressure or cardiac output, the responses in both peripheral resistance and atrial rate increased from minutes 2-3 to minutes 19-20. The responses in peripheral resistance also increased in animals studied after bilateral vagal block. All of the above changes were significant in the majority of cases. In another experiment, the animals were "conditioned" by 20 min at imposed high or low pressure. When control was returned to the animal after conditioning at high pressure, arterial pressure was not significantly different (P greater than 0.05) from the initial control levels. When control was returned after conditioning at low pressure, arterial pressure was significantly greater (P less than 0.05) than during the initial control period. These results indicate an absence of resetting of the entire arterial pressure control system.
Pertussis toxin effects on transmitter release from perivascular nerve terminals
Authors: Nozaki M. , Sperelakis N.
Published: December 2017

Pertussis toxin (PT) was used to investigate the possible involvement of an inhibitory GTP-binding protein (G protein) in neuromuscular transmission at the sympathetic nerve terminal of guinea pig mesenteric artery. When the intracellular microelectrode technique was used, the amount of transmitter released was evaluated by recording the amplitude of excitatory junction potentials (EJPs) in the vascular smooth muscle (VSM) cells. EJPs were evoked by perivascular nerve stimulation with brief square pulses. The amplitude of EJPs was depressed by exogenously applied norepinephrine (NE) (greater than or equal to 10(-7) M) or histamine (greater than or equal to 10(-7) M). However, these effects of NE and histamine on EJP amplitude were almost completely blocked in PT-pretreated VSM cells (2 x 10(-7) g/ml PT, 24 h at 21 degrees C). These effects of PT pretreatment were time and temperature dependent. In contrast, there was no significant change in the resting membrane potential (-70.1 +/- 2.1 mV) or input resistance (11.9 +/- 0.4 M omega) in the VSM cells after PT pretreatment. These results suggest that the effects of NE and histamine on EJP amplitude may be mediated by PT-sensitive G proteins in the presynaptic nerve terminal.