bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin receptor binding and pressor effects in cat subretrofacial nucleus
Authors: Allen A. M. , Dampney R. A. , Mendelsohn F. A.
Published: December 2017

Central administration of angiotensin II (ANG II) increases arterial blood pressure via increased sympathetic activity. We have examined the possibility that one site of action of ANG II is the subretrofacial (SRF) nucleus in the rostral ventrolateral medulla, since this nucleus is known to play a critical role in the tonic and phasic control of arterial pressure. In vitro autoradiography, employing 125I-labeled [Sar1, Ile8]ANG II as radioligand, was used to localize binding sites for ANG II in the cat ventrolateral medulla. A high density of ANG II-receptor binding sites was found confined to the SRF nucleus. In a second group of experiments in anesthetized cats, microinjections of ANG II, in doses ranging from 10 to 50 pmol, were made into histologically identified sites within and outside the SRF nucleus. Microinjections into the nucleus resulted in a dose-dependent increase in arterial pressure, which was abolished by systemic administration of the ganglion-blocking drug hexamethonium bromide. In contrast, microinjections just outside the SRF nucleus had no effect on arterial pressure. It is concluded that activation of ANG II-receptor binding sites within the SRF nucleus leads to an increase in arterial pressure via increased sympathetic efferent activity.
Enhanced cold pressor response in spontaneously hypertensive rats on high-NaCl diet
Authors: Thornton R. M. , Davidson J. M. , Oparil S.
Published: December 2017

This study sought to determine whether spontaneously hypertensive rats (SHR) on a high-NaCl diet have an enhanced pressor response to acute cold exposure and to define the peripheral mechanisms involved in the enhanced pressor response. SHR and normotensive Wistar-Kyoto (WKY) rats that had been on 1 and 8% NaCl diets for 3 wk were subjected to cold exposure. After a 30-min control period, animals were exposed to cold (6 +/- 2 degrees C) for 90 min. Mean arterial pressure (MAP), heart rate (HR), and lumbar sympathetic nerve activity (LSNA) were measured continuously. In a separate group of SHR on 1 and 8% NaCl diets, an arginine vasopressin (AVP) V1 receptor antagonist (10 micrograms/kg iv) was given before cold exposure, and MAP was measured throughout cold exposure. Plasma AVP was measured before and during cold exposure in a separate group of SHR. During cold exposure, there was a significant increase (P less than 0.05) in MAP (25 mmHg) in SHR on the 8% NaCl diet only. In contrast, HR and LSNA increased similarly during cold exposure in both SHR and WKY on the two diets. AVP was similar in both SHR groups (7.1 pg/ml for 1% vs. 6.1 pg/ml for 8%) before cold exposure, but during cold exposure it increased in the 8% NaCl SHR only, reaching 17.6 pg/ml at 90 min. The AVP V1 antagonist completely abolished the cold stress-induced rise in MAP in SHR. Thus SHR on a high-NaCl diet have an enhanced pressor response to acute cold exposure compared with SHR on a normal NaCl diet.(ABSTRACT TRUNCATED AT 250 WORDS)
Combined neurohumoral block modulates pulmonary vascular P/Q relationship in conscious dogs
Authors: Geller H. S. , Nyhan D. P. , Goll H. M. , Clougherty P. W. , Chen B. B. , Murray P. A.
Published: December 2017

Our objective was to investigate the integrated pulmonary vascular response of conscious dogs to combined inhibition of the autonomic nervous system, arginine vasopressin (V1) receptors (vasopressinergic V1), and converting enzyme to identify the overall influence of these three major neurohumoral mechanisms in vascular regulation of the pulmonary circulation. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were generated by graded constriction of the thoracic inferior vena cava, which produced stepwise decreases in Q. When compared with the P/Q relationship measured in intact conscious dogs, combined neurohumoral block resulted in active, nonflow-dependent pulmonary vasodilation. A second objective was to assess the extent to which cyclooxygenase pathway inhibition modified both the intact P/Q relationship and the pulmonary vasodilator response to combined neurohumoral block. Cyclooxygenase inhibition alone (either indomethacin or sodium meclofenamate) resulted in active, nonflow-dependent pulmonary vasoconstriction. Moreover, the pulmonary vasodilation in response to combined neurohumoral block was entirely abolished following cyclooxygenase inhibition. Thus the integrated pulmonary vascular response of conscious dogs to combined neurohumoral block is active vasodilation. This response appears to be mediated by metabolites of the cyclooxygenase pathway.
Control of bat wing capillary pressure and blood flow during reduced perfusion pressure
Authors: Davis M. J.
Published: December 2017

Regulation of blood flow depends on changes in the sum of arterial (Ra) and venous (Rv) resistances, whereas regulation of capillary pressure (Pc) depends on the ratio of Rv to Ra. If the myogenic response of the arterial system (i.e., delta Ra) is the primary mechanism for controlling pressure and flow when perfusion pressure is lowered, then Pc and total flow should be regulated to the same degree under these conditions. This hypothesis was tested by making direct measurements of Pc and flow in skin and skeletal muscle in the wings of unanesthetized bats. The box method was used to reduce perfusion pressure to the wing. Pressures were measured with a servo-null system; flows were computed from measurements of vascular diameters and red cell velocities using intravital microscopy. All branching orders of arterioles dilated significantly during decreases in box pressure (Pb). For 0 less than Pb less than or equal to -30 mmHg, total flow (1st-order arteriolar flow) remained nearly constant, whereas Pc was "regulated" only approximately 60%. These results cannot be explained by changes in arteriolar resistance alone and suggest that changes in Rv may be important. The possible consequences of flow redistribution, capillary recruitment, and micropressure sampling procedures are discussed in relationship to local regulation of capillary pressure and flow.
Lymph flow during increases in pulmonary blood flow and microvascular pressure in dogs
Authors: Grimbert F. A. , Martin D. , Parker J. C. , Taylor A. E.
Published: December 2017

We studied the effects of an increase in pulmonary blood flow (PBF) on steady-state lung lymph flow (QL) and protein transport in anesthetized dogs (n = 7) to estimate the effect of vascular recruitment in zone 3 on transvascular filtration. At the end of each experiment, we increased left atrial pressure to 25-30 mmHg using a balloon catheter and obtained a washdown of the lymph protein concentration. PBF was increased with an extracorporeal circuit, which pumped blood from the left to the right atrium, and increases in pulmonary capillary pressure (Pc) were minimized by lowering left atrial pressure. PBF was measured by thermodilution, and Pc was measured by transient analysis of arterial occlusion pressure with a Swan-Ganz catheter. PBF increases averaged 78% with increases ranging from 36 to 118%. Pc increases ranged from 0.5 to 6.3 mmHg, and QL increases averaged 31% with changes ranging from -2 to +138%. We observed a 16% increase in QL for each 1-mmHg increase in Pc during increased PBF, which was comparable to the relationship previously observed after an increased left atrial pressure. Lymph-to-plasma total protein concentration ratios (CL/CP) decreased from 0.71 +/- 0.04 to 0.625 +/- 0.06 during increased PBF. The relationship between CL/CP, QL, and Pc for both increased blood flow and increased left atrial pressure were within the expected range for increased pressure alone. These data suggest that there was minimal vascular recruitment for transvascular filtration in zone 3 when pulmonary blood flow was increased. Microvascular filtration pressure was the main determinant of fluid and protein transvascular filtration under these conditions.
Decreased vascular contraction and elastic stiffening after intramural lymphostasis
Authors: Berczi V. , Solti F. , Schneider F. , Monos E.
Published: December 2017

Lymphatic obstruction leads to leakage of protein into the vessel wall that is coupled with edema formation and smooth muscle degeneration. To clarify the mechanical effect of these changes, lymphatic trunks, draining the femoral artery, were stained with Evans blue and then ligated in dogs anesthetized with pentobarbital sodium (n = 11). Sham ligation was performed on these lymphatic trunks in the opposite hindlimb (n = 11). Three days later, 7- to 30-mm segments of both femoral arteries were studied in vitro. Intraluminal pressure was cycled between 5 and 250 mmHg at 5 mmHg/s, and external diameter was recorded in both relaxed and activated (norepinephrine, 3 x 10(-5) mol/l) state of smooth muscle. Mechanical parameters were computed for 10-mmHg pressure increments. After lymphatic obstruction, strain energy density and distensibility of the passive wall components as well as isobaric active tangential strain were decreased by a maximum of 27, 59, and 54%, respectively; active tangential stress and elastic modulus, as a function of tangential stretch, was decreased by a maximum of 62%, and increased by 61%, respectively. These results indicate that short-term intramural lymphostasis reduces smooth muscle reactivity and induces vascular stiffening.
In vivo estimation of left ventricular wall volume in volume-overloaded canine hearts
Authors: Feneley M. P. , Gaynor J. W. , Maier G. W. , Gall S. A. , Kisslo J. A. , Rankin J. S.
Published: December 2017

Several geometric algorithms have been applied to estimate left ventricular wall volume (Vwall) from two-dimensional echocardiograms but have not been validated in eccentrically hypertrophied hearts. These algorithms can be fitted to the general formula: Vwall = k.Ao.Lo = k.Ai.Li, where Ao and Ai are the outer (epicardial) and inner (endocardial) short-axis areas, Lo and Li are the corresponding long-axis lengths, and k is a constant. The simplifying assumption that Lo and Li are equal yields Vwall = k.Awall.Lo, where Awall = Ao - Ai. In 20 unsedated dogs (10–30 kg), including 10 with aortic regurgitation of 1–18 wk duration, the relationship between actual Vwall (determined postmortem) and Awall.Lo was not significantly different from the line of identity (Vwall = 1.01 Awall.Lo + 0.5 ml, r = 0.98, SEE = 3.5 ml), indicating k was not significantly different from 1. There was no significant difference between predicted and actual Vwall over a range of 31–105 ml, and interobserver variability was 4.1%. The simple area-length product, Awall.Lo, accurately predicts Vwall of both normal and volume-overloaded hypertrophied canine left ventricles and is thus suitable for serial observations of hypertrophic adaptation to volume overload.
Metabolic hyperemia is reduced in adult vs. immature guinea pig hearts
Authors: Toma B. S. , Wangler R. D. , Sparks H. V.
Published: December 2017

We have previously shown that maturation is associated with decreased maximum coronary flow (CF) elicited pharmacologically or by transient coronary occlusion (Toma, B.S., R.D. Wangler, D.F. DeWitt, and H.V. Sparks. Circ Res. 57: 538-544, 1985). The present study examines the influence of maturation on CF and adenosine release (RADO) during increased myocardial metabolism. Langendorff-perfused hearts from 1- (immature) and 18- (adult) mo-old guinea pigs were given norepinephrine to increase myocardial oxygen consumption (MVO2). CF, oxygen delivery, and venous oxygen tension were significantly lower in the 18-mo-old group for a given MVO2, before and during norepinephrine infusion. Administration of the selective beta-adrenergic agonist isoproterenol, or infusion of norepinephrine during alpha-adrenergic blockade with phentolamine did not significantly increase CF more than norepinephrine at an equivalent MVO2. RADO, relative to MVO2, was greater in 18-mo-old hearts (vs. 1-mo) during norepinephrine infusion. We conclude that in isolated perfused nonworking hearts 1) myocardial metabolic hyperemia decreases during maturation; 2) the observed flow decrement is not the result of increasing alpha-adrenergic activity during maturation; and 3) the flow decrement results in a reduced oxygen supply-to-demand ratio and an increased RADO.
Antiserum to angiotensin-binding protein inhibits vascular responses to angiotensin II
Authors: Webb R. C. , Kiron M. A. , Rosenberg E. , Soffer R. L.
Published: December 2017

This study characterizes inhibitory properties of an antiserum to an angiotensin-binding protein on vascular responses to angiotensin II. The antiserum was collected from guinea pigs that had been immunized with an angiotensin-binding protein that was isolated from a particulate fraction of rabbit liver. The bioassay system consisted of helically cut strips of rabbit renal artery suspended in organ chambers for measurement of isometric force development. After treatment with the antiserum (1:1,000–1:50 dilution), contractile responses to angiotensin II (10(-8) M) were reduced compared with those measured after treatment with nonimmune serum. At a dilution of 1:50, the magnitude of contractile responses to angiotensin II were approximately 40% of control values. This inhibitory action of the antiserum was similar to that induced by the angiotensin II antagonist, saralasin. Contractile responses to norepinephrine (5.9 x 10(-8) M) were not altered after incubation with the antiserum. These results indicate that the binding protein in hepatic cells may be similar in some respects to the membrane receptor mediating contractions to angiotensin II in rabbit renal arteries.
Heart rate and blood pressure changes during sleep-waking cycles and cataplexy in narcoleptic dogs
Authors: Siegel J. M. , Tomaszewski K. S. , Fahringer H. , Cave G. , Kilduff T. , Dement W. C.
Published: December 2017

Cataplexy is the abrupt loss of muscle tone experienced by narcoleptics. It is usually precipitated by strong emotions or athletic activity. It has been hypothesized that cardiovascular variables have a role in the triggering of cataplexy. In the present study, we have utilized the narcoleptic canine model to directly investigate changes in heart rate and blood pressure in relation to cataplectic episodes. We found that heart rate increased 18% on average in the 20 s preceding cataplexy onset and then fell during cataplexy. Thus, from a cardiovascular standpoint, cataplexy can be subdivided into two very different periods, the cataplexy onset period with very high and declining heart rate, and the period greater than or equal to 10 s after onset, with greatly reduced heart rate. Heart rate at cataplexy onset was significantly higher than heart rate in rapid-eye-movement (REM) sleep, non-REM sleep, and quiet waking. Blood pressure did not markedly change before the onset of spontaneous cataplexies but decreased significantly during cataplexy. Although blood pressure increases did not precede spontaneous cataplexies, sudden increases in blood pressure, induced pharmacologically or by obstruction of the descending aorta, triggered cataplexy in the most severely affected subjects. A hypothesized role for cataplexy as a homeostatic reflex, triggered by interactions between blood flow, central chemoreceptors, and atonia control mechanisms in the medial medulla, is discussed.
Characterization of adenosine receptors in human pulmonary arteries
Authors: McCormack D. G. , Clarke B. , Barnes P. J.
Published: December 2017

We have characterized the effects of adenosine, the A1-receptor agonist N6-(L-2-phenylisopropyl)-adenosine (PIA) and the A2-receptor agonist 5'-(N-ethyl)-carboxamido-adenosine (NECA), in isolated human pulmonary vessels. Fresh human lung tissue was obtained from nine patients, and small pulmonary arteries (200-400 micron ID) were dissected and mounted in an organ bath. The effects of the adenosine antagonist 8-phenyltheophylline (8-PT) and endothelial denudation were also studied. Adenosine, NECA, and PIA (1-300 microM) all caused a dose-dependent vasodilation with log EC30 values of -4.31, -4.31, and -3.53, respectively. 8-PT (10 microM) caused a rightward shift of the adenosine dose-response curve, significantly decreasing the effect of adenosine (pKB = 6.3). Mechanical removal of endothelial cells had no significant effect on adenosine-mediated vasodilation. We also compared the effects of adenosine on eight large (7-10 mm ID) and eight small (200-400 micron ID) arteries and found no significant difference in the sensitivity to adenosine between these vessels. Our findings suggest that the pulmonary vasodilator effects of adenosine in humans are mediated through A2 receptors that are localized to vascular smooth muscle. Adenosine may function as a regulator of pulmonary vascular tone in humans and may have therapeutic potential.
Uneven blunting of chronotropic baroreflexes in obese Zucker rats
Authors: Barringer D. L. , Bunag R. D.
Published: December 2017

We compared reflex chronotropic responses to intravenously infused drugs in three groups of age-matched normotensive female rats, namely, Sprague-Dawley, lean Zucker, and obese Zucker. Initial mean pressures did not differ between rat groups, but heart rates tended to be lower in obese Zucker rats. Baroreflex impairment was already evident, because heart rate responses to infused phenylephrine (reflex bradycardia) or sodium nitroprusside (reflex tachycardia) were consistently weaker in obese Zucker than in other rats. Regardless of rat grouping, subsequent cholinergic blockade with atropine elevated, whereas beta-adrenergic blockade with propranolol lowered, basal heart rates without affecting mean pressure. Reflex heart rate responses were all appreciably reduced after either type of autonomic blockade, and although the extent of inhibition varied between rat groups, the residual heart rate responses remaining after blockade were nonetheless always smaller in obese than in lean rats. This difference suggests that efferent sympathetic and parasympathetic mechanisms normally responsible for mediating heart rate reflexes were unevenly blunted in obese Zucker rats.
Effects of lidocaine on sarcolemmal fluidity and cellular cAMP in rat cardiomyocytes
Authors: Roux S. , Escoubet B. , Friedlander G. , Le Grimellec C. , Bertrand I. , Amiel C.
Published: December 2017

Antiarrhythmic drugs with local anesthetic properties modify the physical state of membrane phospholipids and could change adenylate cyclase activity and, thus, influence cardiac ischemic arrhythmias. Adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in cardiomyocytes cultured from newborn rat and fluorescence anisotropy of sarcolemma-enriched membranes were investigated in the presence of a neutral anesthetic drug benzyl alcohol and of a cationic anesthetic drug lidocaine. Benzyl alcohol increased in a dose-dependent manner both sarcolemma fluidity and isoproterenol- or cholera toxin-stimulated cAMP accumulation. In contrast, benzyl alcohol inhibited cAMP accumulation in forskolin-stimulated cells. Lidocaine induced a dose-related inhibition of isoproterenol-, forskolin-, and cholera toxin-stimulated cAMP accumulation without eliciting any change in sarcolemma fluidity. The inhibitory effect of lidocaine on isoproterenol-stimulated cAMP accumulation was reversed when cells were pretreated with pertussis toxin. These data suggest that the inhibitory effect of lidocaine on cAMP synthesis might involve a polar interaction with the Gi regulatory subunit of adenylate cyclase. Such an effect could contribute, in vivo, to both the antiarrhythmic and the negative inotropic effect of lidocaine.
Erythrocytes reduce liquid filtration in injured dog lungs
Authors: Onizuka M. , Tanita T. , Staub N. C.
Published: December 2017

In isolated, dog lung lobes with pulmonary vessels filled with different liquids, we measured the rate of weight gain for 5 or 10 min at constant alveolar and vascular pressures under zone 1 conditions (alveolar pressure greater than vascular pressure). We used six different liquids: syngeneic plasma, whole blood (hematocrit = 38 +/- 4%), 4% albumin in Krebs-Ringer solution, washed red blood cells in Krebs-Ringer solution (hematocrit = 37 +/- 6%), and platelet-rich or platelet-poor plasma. We studied the lobes under three conditions: immediate perfusion after removal (less than 30 min), delayed perfusion (2 h or more), or immediate perfusion after removal from air-embolized animals. In lobes that showed low-filtration rate using plasma [less than 0.5 g/(min x 100 g)] substitution of whole blood had no effect on the filtration rate. In lobes that showed high-filtration rates using plasma (delayed perfusion or deliberately injured using air emboli) substitution of whole blood caused a dramatic decrease in the filtration rate, restoring it to the level obtained in uninjured lobes. Platelets had no effect. Thus the red cells specifically reduced abnormally high filtration but did not affect normal filtration. There appear to be three possible mechanisms: 1) red cells physically blocking large leaks; 2) red cells settling on the filtration surface area (osmotic-barrier effect); 3) red cells acting as reducing agents against active oxygen metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)
X-ray microanalysis of single cardiac myocytes frozen under voltage-clamp conditions
Authors: Wendt-Gallitelli M. F. , Isenberg G.
Published: December 2017

By means of a patch pipette, an isolated ventricular myocyte was transferred into the taper of a silver holder covered by pioloform film. Once the cell was on the film, the cell was voltage clamped (pulses from -45 to +5 mV at 0.5 Hz). The amount of Ca entry was estimated from the Ca current. When contractility (cell shortening) was potentiated with either five pulses of 0.2 s or four pulses of 1 s, shock freezing was timed 116 or 816 ms after start of the clamp pulse. Electron micrographs from freeze-substituted cells revealed the good preservation of the intracellular compartments. The myocytes were cut at -150 degrees C, and the cryosections were freeze dried. In representative examples, the amount of Ca entry is compared with the subcellular Ca distribution as it is analyzed with energy dispersive X-ray microprobe analysis in cytoplasm, junctional sarcoplasmic reticulum (SR), mitochondria, and the subsarcolemmal space (sarcolemma, peripheral SR, fringe of cytosol).
Effect of inosine on pial arterioles: potentiation of adenosine-induced vasodilation
Authors: Ngai A. C. , Monsen M. R. , Ibayashi S. , Ko K. R. , Winn H. R.
Published: December 2017

We examined the cerebral vasoactivity of inosine and its effect on pial arteriolar vasodilation induced by adenosine. Pial circulation was observed through cranial windows implanted in rats anesthetized with halothane. No significant change in venous or arteriolar diameter was apparent when inosine (10(-6) to 10(-3) M) was superfused. In contrast, adenosine in concentrations of 10(-7) and 10(-6) M dilated pial arterioles by 9.0 +/- 1.2 and 17.7 +/- 1.7%, respectively. Addition of 10(-5) M inosine had no effect, whereas 10(-4) M inosine enhanced the vasodilation induced by 10(-7) M adenosine to 19.4 +/- 1.7% and that by 10(-6) M adenosine to 23.3 +/- 2.3%. When theophylline (5 X 10(-5) M) was perfused together with 10(-7) M adenosine and 10(-4) M inosine, the vasodilation was almost completely abolished. The present study indicates that inosine alone does not affect pial vessel diameter but potentiates the response of pial arterioles to exogenous adenosine. This potentiating action of inosine may be attributed to an increase in perivascular adenosine and may be explained by the action of inosine as an adenosine uptake inhibitor.
Responses to acute hypoxemia in fetal sheep at 0.6-0.7 gestation
Authors: Iwamoto H. S. , Kaufman T. , Keil L. C. , Rudolph A. M.
Published: December 2017

A majority of previous studies of fetal responses to acute hypoxemia has focused on the response of the sheep fetus greater than 120 days of gestation when many regulatory systems have been established. To assess the response of younger, less well-developed fetuses, we exposed two groups of fetal sheep (I, 84-91 days; II, 97-99 days gestational age) to acute hypoxemia by giving the ewe a gas mixture containing 9% O2 to breathe. We decreased descending aortic PO2 in both groups of fetuses [I, 24 +/- 6 to 14 +/- 3 (SD) Torr; II, 23 +/- 3 to 12 +/- 4 Torr] by a degree similar to that achieved in previous studies of fetuses greater than 120 days of gestation. Mean arterial blood pressure (I, 31 +/- 6; II, 40 +/- 3 Torr) did not change significantly from control values, and heart rate (I, 224 +/- 27; II, 203 +/- 16 beats/min) increased significantly in group II fetuses with hypoxemia. In group I and II fetuses, as in older fetuses, cerebral, myocardial, and adrenal blood flows, measured by the microsphere technique, increased, and pulmonary blood flow decreased. These responses mature early and are likely local vascular responses to decreases in oxygen content. Combined ventricular output and umbilical-placental blood flow decreased significantly in both groups. Unlike the response of the fetus greater than 120 days, acute hypoxemia did not decrease blood flow to the musculoskeletal and cutaneous circulations (group I only), gastrointestinal, or renal circulations.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of hypoglycemia on cerebral metabolism and carbon dioxide responsivity
Authors: Sieber F. E. , Derrer S. A. , Saudek C. D. , Traystman R. J.
Published: December 2017

This study examined the effects of hypoglycemia (HG) on cerebral metabolism and cerebrovascular reactivity to carbon dioxide. Cerebral blood flow (CBF) was determined using radiolabeled microspheres in pentobarbital-anesthetized dogs. Cerebral oxygen, glucose, lactate, pyruvate, acetoacetate, and beta-hydroxybutyrate uptakes were calculated using the respective concentrations measured in arterial and sagittal sinus blood samples. EEG was recorded throughout each experiment. HG was induced with insulin to obtain a blood glucose less than 30 mg/100 ml. Hypercapnia was studied in 10 animals (3 control, 7 HG) by increasing arterial carbon dioxide tension (PaCO2) from control (35 +/- 4; mean +/- SE) to 54 +/- 2 Torr during normoglycemia (NG) and HG. Hypocapnia was studied in 11 animals (3 control, 8 HG) by decreasing PaCO2 from control (39 +/- 1) to 14 +/- 1 Torr in NG and HG. Measurements were taken after reaching steady-state PaCO2 in both groups at each control and altered PaCO2 state. In the hypercapnic group, glucose decreased from 71 +/- 3 to 28 +/- 3 mg/100 ml. CBF increased with hypercapnia to 175% of control in both NG and HG. Cerebral metabolic rate of oxygen and electroencephalogram (EEG) did not change in the hypercapnic group. In the hypocapnic group glucose decreased from 71 +/- 3 to 19 +/- 2 mg/100 ml. CBF decreased with hypocapnia to 62 +/- 5% of control in NG but remained at control in HG. This was not accompanied by changes in cerebral oxygen consumption; however, a flat EEG occurred in all HG hypocapnic animals. No change occurred in uptake of the other cerebral metabolites measured in any group. This study shows that the CBF hypercapnic response remains intact during HG; however, hypocapnia causes severe EEG disturbances and impairs the cerebral vasoconstriction response.
Regional variation in rat cardiac myosin isoenzymes and ATPase activity after infarction
Authors: Geenen D. L. , Malhotra A. , Scheuer J.
Published: December 2017

Three and 11 wk after coronary artery ligation in rats, the right and left ventricular free wall, septum, and papillary muscles from infarcted and sham-operated hearts were analyzed to determine whether regional variability existed in cardiac actomyosin adenosine triphosphate (ATPase) activity and myosin isoenzymes. Infarction produced a 74% greater right ventricular mass and 19% greater septal mass compared with sham-operated hearts at 3 wk. There was no additional increase in cardiac mass associated with infarction from 3 to 11 wk above that expected for normal growth. Actomyosin ATPase activity and the percent V1 myosin heavy-chain isoenzyme decreased significantly in all regions of the infarcted heart by 3 wk. In addition, the left ventricular and papillary muscle of infarcted hearts exhibited a decrease in percent V1 myosin of 18 and 35%, respectively, compared with the right ventricular free wall and septum. These differences persisted at 11 wk, although no further depression of actomyosin ATPase activity or shift in myosin isoenzyme distribution were observed over the 8-wk period. These results demonstrate that myocardial infarction induces a shift in the myosin isoenzyme distribution and depression in actomyosin ATPase activity of surviving cardiac tissue. Regional variability in myosin isoenzymes is evident by 3 wk, but additional adaptation in cardiac mass and myosin biochemistry do not occur beyond this time.
Cytoplasts and Mo1-deficient neutrophils pretreated with plasma and LPS induce lung injury
Authors: Wencel M. L. , Morganroth M. L. , Schoeneich S. O. , Gannon D. E. , Varani J. , Todd R. F. , Ryan U. S. , Boxer L. A.
Published: December 2017

We hypothesized that neutrophil adhesion and lung injury could occur independent of the surface receptor glycoprotein, Mo1 (C3bi receptor). We investigated whether preincubation of human neutrophil-derived cytoplasts (cell fragments that lack nuclei and granules and have a fixed number of surface Mo1 receptors) with plasma and lipopolysaccharide (LPS) would augment the cytoplasts' ability to cause lung injury when activated. We also investigated whether preincubating normal human neutrophils treated with anti-Mo1 antibody with plasma and LPS would increase the neutrophils' ability to adhere and cause lung injury. Human neutrophils infused into isolated salt-perfused rat lungs subsequently stimulated with phorbol 12-myristate 13-acetate (PMA) resulted in lung injury as assessed by the accumulation of 125I-bovine serum albumin in the lung parenchyma. The infusion of cytoplasts resulted in significantly less injury. Cytoplasts preincubated in 20% human plasma and LPS caused an increase in lung injury. Similarly, neutrophils treated with plasma, LPS, and anti-Mo1 antibody or neutrophils congenitally deficient in the Mo1 surface receptor and treated with plasma and LPS augmented lung injury. Plasma and LPS preincubation also increased anti-Mo1 antibody-treated neutrophil adhesion to endothelial cell monolayers after activation by PMA. Thus, plasma and LPS increase adhesion and lung injury caused by neutrophils or neutrophil fragments that share defects in Mo1 receptor expression.
Proximal and distal dog coronary arteries respond differently to basal EDRF but not to NO
Authors: Hoeffner U. , Boulanger C. , Vanhoutte P. M.
Published: December 2017

Experiments were designed to analyze the effects of endothelium-derived relaxing factor(s) (EDRF; released basally or on stimulation with acetylcholine) and nitric oxide (NO) on smooth muscle of coronary arteries of different diameter. During contractions of the bioassay ring evoked with prostaglandin F2 alpha, the relaxations caused by basal EDRF were greater in the distal than in the proximal coronary arteries, whereas there was no difference in response to the EDRF released by acetylcholine. During direct superfusion, NO caused similar relaxations in proximal and distal coronary artery rings. Optimal tension, prostaglandin F2 alpha-induced contractions, and relaxations caused by sodium nitroprusside were comparable in both preparations. In rings of proximal and distal coronary artery studied in organ chambers, acetylcholine caused comparable endothelium-dependent, whereas sodium nitroprusside and NO cause comparable endothelium-independent relaxations. These experiments indicate a difference in response of different-sized coronary arteries to basally released EDRF and suggest that the basally released factor differs from NO.
Propagation of vasomotor responses coordinates arteriolar resistances
Authors: Segal S. S. , Damon D. N. , Duling B. R.
Published: December 2017

We tested the hypothesis that a conduction pathway intrinsic to the arteriolar wall possesses the properties necessary to coordinate vasomotor responses in the microcirculation. Acetylcholine (ACh) or norepinephrine (NE) was iontophoresed onto cheek pouch arterioles (15-35 microns diam) of pentobarbital-anesthetized hamsters, and diameter responses were observed using intravital video microscopy. ACh and NE induced vasodilation and vasoconstriction, respectively, that propagated both upstream and downstream from the site of application. Propagated vasomotor responses decayed with distance along the arterioles; this decay was characterized by mechanical length constants of 1.9 and 1.8 mm for ACh and NE, respectively. Vasodilations and vasoconstrictions initiated on daughter vessels of a branch propagated into parent arterioles that were approximately twice the diameter of the daughter vessels. Iontophoretic stimuli applied simultaneously to paired daughter vessels induced propagated responses that summed linearly in the parent vessel. We conclude that the arteriolar network functions as a highly coordinated syncytium and that diverse vasomotor stimuli can be summed and integrated within the peripheral microvasculature.
Effects of intracellular alkalinization on resting and agonist-induced vascular tone
Authors: Danthuluri N. R. , Deth R. C.
Published: December 2017

To evaluate the influence of intracellular alkalinization on basal and agonist-induced vascular tone, we studied the effect of NH4Cl on rat aorta. NH4Cl induced a gradually developing contraction in a dose-dependent manner. Although the contractile response to 20 mM NH4Cl was associated with a latent period (LP) of 23.4 +/- 2.8 min, intracellular pH (pHi) measurements in cultured rat aortic smooth muscle cells showed that NH4Cl-induced intracellular alkalinization was immediate and transient, returning to basal pHi levels in about 30-35 min. Agents that elevate Ca2+, such as A23187 and high KCl, significantly reduced the LP associated with 20 mM NH4Cl-induced contraction. NH4Cl-induced contractions were sensitive to extracellular Ca2+ removal and to the addition of forskolin (1 microM); however, NH4Cl by itself did not cause Ca2+-influx as shown by 45Ca-uptake studies. Addition of 20 mM NH4Cl to precontracted tissues resulted in a transient relaxation, which was complete in approximately 10 min, followed by a contraction above the original level of tone. NH4Cl pretreatment caused time-dependent alterations in both the rapid and slow phases of phenylephrine and angiotensin II contractions. Rapid-phase of phenylephrine and angiotensin II contractions. Rapid-phase responses were diminished at shorter NH4Cl incubation times (10 min), whereas slow-phase response was augmented after a longer incubation (20 min). Overall, the vasorelaxant and vasoconstrictor effects induced by NH4Cl suggest a complex relationship between intracellular alkalinization and arterial contractility.
Whole body autoregulation in conscious areflexic rats during hypoxia and hyperoxia
Authors: Hinojosa-Laborde C. , Greene A. S. , Cowley A. W.
Published: December 2017

We have previously shown whole body autoregulation during normoxia in conscious areflexic rats in response to an acute increase and decrease in blood volume. In this study we used this technique to determine the effect of hypoxia and hyperoxia on whole body autoregulation. Rats with an arterial catheter for blood pressure measurement and an electromagnetic flow probe for cardiac output measurement were placed in a chamber with a controlled oxygen environment. Neurohumoral blockade was achieved with chlorisondamine (10 mg/kg), methscopolamine (0.5 mg/kg), captopril (1 mg/kg), and [d(CH2)5Tyr(Me)]arginine vasopressin (10 micrograms/kg). Hemodynamic variables were restored to normal with a constant norepinephrine infusion. Group 1 (n = 7) underwent a 6-min infusion of donor blood (0.9 ml) during hypoxia (Po2 = 52 +/- 3 mmHg) and hyperoxia (Po2 = 296 +/- 12 mmHg). Group 2 (n = 8) was subjected to a 6-min withdrawal of blood (0.9 ml) during hypoxia (72 +/- 2 mmHg) and hyperoxia Po2 = 258 +/- 8 mmHg). The slope of the pressure-flow relationship was used as an index of autoregulation so that a slope of 0 indicated complete autoregulation and a slope of 1 represented no autoregulation. The pressure-flow slopes with volume expansion were 0.54 during hypoxia and 0.15 during hyperoxia, while the slopes with volume contraction were 0.29 during hypoxia and 0.54 during hyperoxia. Thus, when arterial pressure was raised above normal, the autoregulatory capacity was greater during hyperoxia than with hypoxia. Conversely, when arterial pressure was lowered below normal, the autoregulatory capacity was greater during hypoxia than with hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
Neurohumoral changes during onset and offset of ovine heart failure: role of ANP
Authors: Fitzpatrick M. A. , Nicholls M. G. , Espiner E. A. , Ikram H. , Bagshaw P. , Yandle T. G.
Published: December 2017

The temporal relationship of changes in atrial natriuretic peptide (ANP) secretion to other pathophysiological changes in heart failure has not been investigated. We studied the hemodynamic, hormonal, and metabolic changes before, during, and after the induction of heart failure in eight sheep using a 14-day period of rapid left ventricular pacing (LVP). Arterial pressure declined 21% on the first day, while cardiac output fell progressively to 48% of base line, and atrial pressures rose to a plateau over the first week. Plasma ANP levels increased 10-fold with a close correlation to left atrial pressure in all sheep. Furthermore, ANP secretion appeared to be sustained throughout the LVP period but did not prevent avid sodium retention. Marked and early activation of the renin-angiotensin system was observed, whereas the major increase in plasma aldosterone commenced 4 days later. On termination of LVP, a prompt natriuresis and diuresis occurred with return of all parameters toward base line. Thus this ovine model is useful for studying pathophysiological changes during the onset and offset of heart failure.
Reflex control of mesenteric vein diameter and pressure in situ in rabbits
Authors: Ozono K. , Bosnjak Z. J. , Kampine J. P.
Published: December 2017

We have directly demonstrated that the mesenteric veins actively constrict and dilate in response to reflex stimuli in the in situ preparation. A segment of small intestine of 23 chloralose-anesthetized rabbits was exposed in a specially designed bath. Small vein diameter and intravenous pressure (575-1,375 microns and 6.2-11.4 mmHg at rest, respectively) of the mesentery were measured continuously at the same site with the use of videomicrometer and micropressure systems during celiac ganglion stimulation (CGS), bilateral carotid occlusion (BCO), and aortic nerve stimulation (ANS). Innervation to the mesenteric vein was evident by a frequency-dependent venoconstriction in response to CGS, which was completely abolished by local application of tetrodotoxin. Vein diameter and intravenous pressure changed from an average of 1,042 +/- 32 to 1,003 +/- 32 microns (-3.8 +/- 0.3%, P less than 0.01) and from 8.1 +/- 0.3 to 9.0 +/- 0.3 mmHg (10.6 +/- 0.8%, P less than 0.01), respectively, during BCO. During ANS, vein diameter increased from 990 +/- 32 to 1,012 +/- 31 microns (2.4 +/- 0.2%, P less than 0.01), and intravenous pressure decreased from 8.5 +/- 0.3 to 7.9 +/- 0.2 mmHg (-6.1 +/- 0.6%, P less than 0.01), respectively. Vein diameter changes of -3.8 and 2.4% corresponded to volume changes of -7.6 and 4.9%, respectively. During BCO, vein diameter decreased while intravenous pressure increased, whereas during ANS vein diameter increased while intravenous pressure decreased. These results indicate that the reflex change in vein diameter is due to an active response.
Coronary flow during exercise after selective alpha 1- and alpha 2-adrenergic blockade
Authors: Dai X. Z. , Sublett E. , Lindstrom P. , Schwartz J. S. , Homans D. C. , Bache R. J.
Published: December 2017

This study was carried out to determine the relative importance of alpha 1- and alpha 2-adrenergic vasoconstriction in opposing the increase in coronary blood flow, which occurs during exercise. The response of left circumflex coronary artery blood flow was examined during treadmill exercise in 16 chronically instrumented dogs during control conditions, after selective alpha 1-adrenergic blockade with intracoronary prazosin, and after alpha 2-blockade with intracoronary idazoxan. During control conditions, graded treadmill exercise resulted in progressive increases of coronary blood flow and decreases of coronary vascular resistance. Prazosin produced highly selective alpha 1-adrenergic blockade; coronary blood flow was significantly higher and coronary vascular resistance significantly lower during all but the heaviest exercise stage after prazosin. Idazoxan produced highly effective, but only moderately selective, alpha 2-adrenergic blockade. However, after idazoxan, coronary blood flow and coronary vascular resistance during exercise were not significantly different from control. Combined alpha 1- and alpha 2-adrenergic blockade was not more effective in increasing coronary blood flow during exercise than was alpha 1-adrenergic blockade alone. These data support a role for alpha 1-adrenergic coronary vasoconstriction in limiting the increase in coronary blood flow, which occurs during exercise, but do not support a role for alpha 2-mediated coronary vasoconstriction during exercise.
Cellular K+ loss and anion efflux during myocardial ischemia and metabolic inhibition
Authors: Weiss J. N. , Lamp S. T. , Shine K. I.
Published: December 2017

It has been suggested that increased K+ efflux during myocardial hypoxia and ischemia may result from efflux of intracellularly generated anions such as lactate and inorganic phosphate (Pi) as a mechanism of balancing transsarcolemmal charge movement. To investigate this hypothesis cellular K+ loss using 42K+ and K+-sensitive electrodes, intracellular potential, venous lactate and Pi, and tissue lactate and high-energy phosphates were measured in isolated arterially perfused rabbit interventricular septa during exposure to metabolic inhibitors, hypoxia, and ischemia. Selective inhibition of glycolysis caused a marked increase in K+ efflux despite a fall in lactate production and maintenance of normal cellular high-energy phosphate content. During ischemia and hypoxia net loss of lactate and Pi exceeded K+ loss by a factor of 2-6. However, removal of glucose prior to ischemia or during hypoxia increased K+ loss but reduced lactate loss without affecting Pi loss. During hypoxia, 30 mM exogenous lactate did not alter K+ loss in a manner consistent with changes in passive electrodiffusion of lactate ion. These findings inhibition which is not related to anion efflux assumes greater importance under conditions in which glycolysis is inhibited, e.g., ischemia. Under conditions in which glycolysis is not inhibited, e.g., hypoxia, K+ efflux does not parallel passive electrodiffusion of lactate ions. However, this finding does not exclude the possibility that K+ loss could be coupled to carrier-mediated lactate ion efflux.
Beta-receptor-adenylate cyclase coupling in hypoxic neonatal rat ventricular myocytes
Authors: Thandroyen F. T. , Muntz K. , Rosenbaum T. , Ziman B. , Willerson J. T. , Buja L. M.
Published: December 2017

This study investigated the influence of hypoxia on alterations in the beta-adrenergic receptor-adenylate cyclase system. Cultured neonatal rat ventricular myocytes were subjected to normoxia (incubator PO2 135-145 mmHg) or hypoxia (incubator PO2 0-14 mmHg) and, in crude membrane preparations, beta-receptor binding properties were measured with [125I]iodocyanopindolol and adenylate cyclase activity by radioimmunoassay. Hypoxia of 30 min in duration caused no alteration in beta-receptor density (Bmax 75 +/- 11 vs. 71 +/- 12 fmol/mg protein) but increased adenylate cyclase activity under basal conditions and during stimulation with l-isoproterenol, 5'-guanylimidotriphosphate [Gpp(NH)p] 5 X 10(-5) M, NaF 10(-4) M, and forskolin 10(-4) M. For example, isoproterenol 10(-5) M + guanosine 5'-triphosphate (GTP) 5 X 10(-5) M gave 221 +/- 34 vs. 143 +/- 11 pmol.min-1.mg protein-1, P less than 0.05 hypoxia vs. normoxia. After 60 min of hypoxia, adenylate cyclase activity was no longer increased. Hypoxia of 120-150 min duration increased Bmax by 64% (73 +/- 8 to 120 +/- 11 fmol/mg protein, P less than 0.05 vs. normoxia) but decreased adenylate cyclase activity during stimulation with isoproterenol, NaF 10(-4) M, and forskolin 10(-4) M. For example, isoproterenol 10(-5) M + GTP 5 X 10(-5) M gave 107 +/- 12 vs. 148 +/- 11 pmol.min-1.mg protein-1, P less than 0.05 hypoxia vs. normoxia. Reoxygenation for 15 min following 120-150 min of hypoxia reversed the increased beta-receptor numbers and decreased adenylate cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Monophasic action potential recordings in response to graded hyperkalemia in dogs
Authors: Sutton P. M. , Taggart P. , Spear D. W. , Drake H. F. , Swanton R. H. , Emanuel R. W.
Published: December 2017

Recent interest in sudden cardiac death during exercise in normal healthy people has highlighted the possible role of swings of extracellular potassium in arrhythmogenesis in conditions other than ischemia. Regional differences in action potential duration and conduction may be important. We have recorded monophasic action potentials (MAPs) from the endocardium and epicardium in nine open-chest dogs during graded intravenous infusion of potassium up to a plasma level of 9 mM. The animals were anesthetized with alpha-chloralose and urethan. Continuous, online arterial potassium monitoring was employed. MAP duration showed a biphasic response with initial shortening up to 7 mM, which tended to be more obvious on the epicardium. Regional activation time was measured as the difference between the onset of depolarization of the endocardial and epicardial MAP. Regional activation time also showed a biphasic response with initial shortening and subsequent delay. The QRS width of the scalar lead II electrocardiogram also showed biphasic changes, and the T wave amplitude progressively decreased. Our results suggest that regional differences in repolarization time may develop in the nonischemic myocardium in response to increased extracellular potassium levels mainly as a result of local changes in regional activation time rather than as a result of a direct effect on action potential duration.
Heart failure depresses endothelium-dependent responses in canine femoral artery
Authors: Kaiser L. , Spickard R. C. , Olivier N. B.
Published: December 2017

Vascular responses to many physiological stresses are abnormal in heart failure. Increased peripheral resistance and a reduction in the vasodilator response to exercise and ischemia are examples of this abnormal vascular control. Such abnormal vascular control in heart failure is a result of interplay between neural, hormonal, and local vascular factors. This study was designed to test the hypothesis that a specific local mechanism, endothelium-dependent relaxation to acetylcholine (ACh), is depressed in experimental heart failure. Experiments were performed on 11 purebred beagles. Experimental heart failure was induced by rapid ventricular pacing for approximately 30 days. Femoral artery diameter was measured by sonomicrometry, and dose-response relationships to ACh, norepinephrine (NE), and nitroglycerin (NTG) were done before and after inhibition of cyclooxygenase by indomethacin. Heart failure resulted in a significant depression of ACh relaxation at all concentrations. In dogs with heart failure, indomethacin enhanced the dilation response to low concentrations of ACh. Constriction to NE and dilation to NTG were unchanged by heart failure. These data demonstrate that in the canine femoral artery endothelium-dependent dilation to ACh is depressed in experimental heart failure. Depression of endothelium-dependent vasodilation represents one local mechanism for abnormal control of the vasculature in congestive heart failure.