bluuebunny/crossref_metadata_2025 huggingface dataset:
Reflexes fail to reduce pressor activity of vasopressin in spontaneous hypertension
Authors: Datar S. , Chiu E. K. , McNeill J. R.
Published: December 2017

Pressor responses and heart rate responses were recorded in spontaneously hypertensive rats (SHR) and in Wistar-Kyoto (WKY) rats during intravenous infusions of arginine vasopressin and phenylephrine under two experimental situations, first when cardiovascular reflexes were impaired by pretreatment with a ganglionic blocking agent (pentolinium) and second, when reflexes remained intact. In rats with ganglia blocked, pressor responses of SHR to vasopressin or to phenylephrine were similar to those of WKY rats. In rats with intact reflexes, pressor responses of SHR to phenylephrine were also similar to those of WKY rats but, in contrast, pressor responses of SHR to vasopressin were enhanced. Heart rate fell much more for any given elevation of blood pressure in WKY rats than in SHR during infusions of vasopressin and phenylephrine, and the bradycardia associated with these pressor agents was largely abolished by pentolinium. The results are consistent with the hypothesis that baroreflexes buffer the pressor activity of vasopressin in the normotensive WKY rat and that an impairment of baroreflex activity in SHR contributes to the enhanced pressor activity of vasopressin in these rats.
Effects of ouabain, low K+, and aldosterone on hypoxic pressor reactivity of rat lungs
Authors: Herget J. , McMurtry I. F.
Published: December 2017

It can be postulated that inhibition of lung tissue Na+-K+-ATPase might potentiate hypoxic pulmonary vasoconstriction by depolarizing some excitable cell or, in contrast, that it might blunt the hypoxic response by reducing cellular metabolic rate and sensitivity to hypoxia. Thus the purpose of this study was to test in isolated rat lungs whether hypoxic pressor reactivity was related inversely or positively to Na+-K+-ATPase activity. Dose-pressor response curves to hypoxia, angiotensin II, or KCl were measured under control conditions and after exposure either to one of two inhibitors of Na+-K+-ATPase, ouabain, and low-K+ solution or to a stimulator of Na+-K+ pumping, aldosterone. Ouabain and low K+ depressed the response to hypoxia but had little effect on that to angiotensin II. The response to KCl was increased by ouabain. Aldosterone potentiated the hypoxic response. These results do not support the idea that membrane depolarization due to inhibition Na+-K+ pumping is a component of hypoxic vasoconstriction. They do suggest a positive relationship between Na+-K+-ATPase activity and hypoxic pressor reactivity and are consistent with the idea that Na+-K+-ATPase activity might influence hypoxic reactivity indirectly by altering cellular energy metabolism. It is also possible that the results were somehow due to changes in intracellular [Na+] or transmembrane Na+ gradient, rather than to changes in energy metabolism.
Regional blood flow distribution during the Cushing response: alterations with adrenergic blockade
Authors: van Wylen D. G. , D'Alecy L. G.
Published: December 2017

Regional blood flow distribution (microspheres) and cardiac output (CO, thermal dilution) were measured during the Cushing response in unblocked (UB), beta-receptor-blocked (BB, 2 mg/kg propranolol iv), or alpha-receptor blocked (AB, 0.5 mg/kg + 0.5 mg X kg-1 X min-1 phentolamine iv) chloralose-anesthetized dogs. Intracranial pressure was increased to 150 mmHg by infusion of temperature-controlled artificial cerebrospinal fluid into the cisterna magna. Similar increases in mean arterial pressure were seen in UB and BB, but in AB a Cushing response could not be sustained. In UB, cerebral blood flow (CBF) decreased 50%, coronary blood flow (CoBF) increased 120%, and peripheral tissue blood flow was reduced only in the kidneys (18%) and the intestines (small 22%, large 35%). Blood flow to the other viscera, skin, and skeletal muscle was unchanged. CO (16%) and heart rate (HR, 38%) decreased, and total peripheral resistance (TPR, 68%) and stroke volume (SV, 38%) increased. In BB, CBF decreased 50%, CoBF decreased 20%, and blood flow was reduced 40-80% in all peripheral tissues. CO (69%) and HR (62%) decreased, TPR increased 366%, and SV was unchanged. We conclude that the Cushing response in UB animals combines an alpha-receptor-mediated vasoconstriction with a beta-receptor cardiac stimulation. The beta-mechanism is neither necessary nor sufficient for the hypertension. However, the combination of alpha- and beta-adrenergic mechanisms maintains cardiac output and peripheral tissue blood flow relatively constant while producing a systemic hypertension.
Stimulation of lipolysis in rat heart myocytes by isoproterenol
Authors: Kryski A. , Kenno K. A. , Severson D. L.
Published: December 2017

Calcium-tolerant myocytes were isolated from rat hearts. Isoproterenol produced a dose-dependent increase in glycerol output (lipolysis) that could be blocked by propranolol. The presence of glucose in the incubation medium enhanced the release of glycerol from myocytes but had no effect on the decline in triacylglycerol content. No incorporation of radioactivity from [U-14C]glucose into glycerol could be detected. In incubations with isoproterenol, there was a stoichiometric relationship between the glycerol output and the decrease in triacylglycerol levels. The addition of the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine resulted in an increase in the basal glycerol output and an enhancement of the isoproterenol-stimulated lipolytic rate. Forskolin and 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate also produced a concentration-dependent stimulation of lipolysis in myocytes. Therefore, lipolysis in isolated myocytes must be regulated by adenosine 3',5'-cyclic monophosphate-dependent mechanisms. These results demonstrate that lipolysis can be observed in myocardial cells and that the lipolytic response to isoproterenol cannot be secondary to a physiological (inotropic) response since these myocyte preparations are quiescent.
Microsphere passage through intestinal circulation: via shunts or capillaries?
Authors: Maxwell L. C. , Shepherd A. P. , McMahan C. A.
Published: December 2017

Significant quantities of 9-micron microspheres (20-30%) are not trapped in the intestine following intracardiac or intra-arterial injection, but reach venous blood. Some investigators propose that the passage of 9-micron spheres measures blood flow through noncapillary connections. Because frequency distributions of intestinal capillary diameters and 9-micron spheres overlap, microspheres could simply pass through capillaries. Therefore, we developed simple probabilistic models to predict both the size distribution and the percentage of injected spheres [9 +/- 1 (SD) micron] that should appear in venous blood. Chief assumptions in models are that microsphere delivery and sphere diameter are independent and that microspheres pass through capillaries of equal or larger size. The passage predicted by the models was consistent with values in canine intestinal circulation, demonstrating that passage through capillaries [7.38 +/- 1.4 (SD) micron] adequately accounts for spheres in venous blood. Because the diameters of nominal 9-micron spheres were distributed too narrowly to show a marked sieving effect on passage through the intestinal circulation, we also injected microspheres varying from 5 to 20 micron in diameter. This mixture demonstrated a marked sieving effect. The predicted frequency distribution for microsphere diameters in venous blood agreed with the observed distribution. Our models demonstrate that the passage of 9-micron spheres through capillaries, rather than through “shunts,” adequately accounts for the appearance of spheres in venous blood and suggests that the frequency distribution of venous microspheres can provide an in vivo method for estimating the frequency distribution of intestinal capillary diameters.
Vasomotor response to hormonal norepinephrine in canine cerebral and hindlimb vessels
Authors: Louie J. A. , Javid M. J. , Gilboe D. D.
Published: December 2017

We calculated the percent change in initial vascular resistance during open loop intra-arterial infusions of norepinephrine (NE) in 12 acutely denervated isolated canine brains and 5 acutely denervated perfused hindlimbs. The studies were repeated on seven chronically denervated brains devoid of perivascular sympathetic fibers. All tissues were free of residual anesthetic. Half-maximal responses were obtained at similar plasma NE concentrations in both the control brains (ED50 13.1 +/- 3.8 X 10(-6) M) and hindlimbs (ED50 9.22 +/- 2.3 X 10(-6). The maximal response was much greater in the limb vasculature (490.3 +/- 30.1%) than in the cerebral vasculature (107.2 +/- 9.5%). A fourfold increase in cerebral vascular sensitivity was noted 3 days after sympathetic gangliectomy (ED50 3.44 +/- 0.74 X 10(-6) M), without any significant change in the maximal response (101.3 +/- 5.7%). Plasma levels of NE observed in resting dogs did not constrict either vascular bed; elevated levels of NE observed in stress dogs would minimally constrict limb vessels but not acute or chronically denervated cerebral vessels. These in situ results confirm that NE does not play a significant role as a physiological vasomotor hormone and suggest that prejunctional neuronal uptake of NE is not responsible for the observed differences in cerebral and hindlimb vascular response. Furthermore, it is unlikely that denervation hypersensitivity to circulating NE plays a role in pathological cerebral vasoconstriction (vasospasm) following subarachnoid hemorrhage.
Mathematical models of arterial transmural transport
Authors: Fry D. L.
Published: December 2017

A finite-element model (FEM) and corresponding five-parameter analytical model (AM) were derived to study the one-dimensional transport of chemically reactive macro-molecules across (x) arterial tissue. Derivations emphasize chemical activity [a(x)], its gradient, and water flux as driving forces for chemical reactions and transport. The AM was fitted to 28 measured 125I-albumin transmural concentration [c(x)] curves giving parameter estimates of diffusivity (DA), convective velocity (nu A), and so on as functions of pressure (P), location (z) along the vessel, etc. The FEM was used to study 1) intimal-medial a(x) associated with molecular sieving and medial edema, 2) reversible binding, and 3) errors of AM in analysis of c(x). Results are as follows. Average relative error for the 28 AM fits was 5.3%. Only estimates of DA and nu A had acceptable coefficients of variation. DA (approximately 0.10 X 10(-7) cm2 X s-1) decreased with P, increased with z to a maximum, and then decreased; nu A was approximately proportional to P (approximately 0.12 X 10(-7) cm X s-1 X mmHg-1) and decreased slightly with z; distribution coefficient (epsilon F) decreased with z and was smaller for serum than for simple albumin reagent. Assumed boundary conditions for AM were associated with approximately 1.4% error in AM c(x). Parameter estimates were sensitive to wall inhomogeneity, e.g., approximately 15% error. In conclusion, the AM and FEM simulated measured c(x) well; the FEM is useful for study of mechanisms, experimental designs, and AM errors; trends of AM parameter estimates suggest dependence on P, z, and composition of reagent for further FEM and experimental study.
Drop-counting flow computer
Authors: Burgar C. G. , Winter G. J. , Shepherd A. P.
Published: December 2017

An inexpensive microcomputer (VIC-20) was adapted to count drops of fluid and calculate flow. To minimize both the expense and the bench space occupied by the flow computer, we eliminated the need for a video monitor by employing a liquid crystal alphanumeric display. Neither tape recorders nor disk drives are needed because the flow-computing program resides in a “game cartridge.” Furthermore, the power supply of the computer powers the interface and display. The computer's real-time clock is utilized to time intervals between drops falling through an infrared beam. The computed flow values are then shown on the liquid crystal display, and they are sent to an external recorder via a digital-to-analog converter. A second digital-to-analog converter can be used to trigger a fraction collector. When compared with timed manual collections, the flow computer was shown to yield highly accurate, linear measurements of water and blood flow. Although the drops-per-milliliter constant varied with orifice size and hematocrit, the hematocrit fluctuations observed in typical isolated organ experiments would not appreciably affect the blood flow determinations.
Phenothiazine suppression of transient depolarizations in rabbit ventricular cells
Authors: Kremers M. S. , Kenyon J. L. , Ito K. , Sutko J. L.
Published: December 2017

We have examined the effects of trifluperazine and fluphenazine on action potentials and transient depolarizations of rabbit ventricular cells. Isolated myocytes were prepared by perfusing rabbit hearts with low calcium enzyme-containing solutions, and action potentials were stimulated at 1 Hz and recorded using patch-type pipettes. In normal saline, 10 microM trifluperazine or fluphenazine shifted the action potential plateau to more negative potentials and increased the rate of phase 2 repolarization. Transient diastolic depolarizations appeared in solutions containing 50 nM isoproterenol plus 1 microM strophanthidin. These transient depolarizations were abolished by the addition of 10 microM trifluperazine or fluphenazine. In addition, spontaneous transient depolarizations were occasionally observed, and these too were abolished by the phenothiazines. Because these compounds are potent inhibitors of calmodulin, these data raise the possibility that calcium-calmodulin-regulated processes are important in the generation of arrhythmogenic transient depolarizations.
Isomyosin and thyroid hormone levels in pressure-overloaded weanling and adult rat hearts
Authors: Martin A. F. , Robinson D. C. , Dowell R. T.
Published: December 2017

We examined the relationship between ventricular isomyosin composition and plasma thyroxine (T4) 5 wk after partial constriction of the abdominal aorta in weanling (21 day) and adult (8 wk) rats. Cardiac enlargement in weanling aorta-constricted animals was associated with a significant (P less than 0.001) decrease in %V1 isomyosin in both left (32%) and right ventricles (25%) with a corresponding increase in the %V3 isomyosin and a reduction in plasma T4 levels. However, the ratio of V1/T4 was similar in weanling control (17.8 +/- 0.8) and aorta-constricted (18.0 +/- 1.4) rats. In adult aorta-constricted animals, there was a significant (P less than 0.001) reduction in the %V1 (16%) isomyosin in the left ventricle and a smaller decrease in the right ventricular V1 (8%) with no change in plasma T4 levels. There was also a significant difference in V1/T4 between control (16.1 +/- 0.4) and aorta-constricted (13.9 +/- 0.7) adult rats in contrast to the maintenance of the V1/T4 in weanling aorta-constricted animals. Thus both increased workload and changes in thyroxine levels contribute to the isomyosin redistribution seen in weanling rats subjected to a pressure overload, whereas, in adult hypertrophied hearts, alterations of the ventricular isomyosin composition appear to be due solely to the increased pressure overload.
Distribution of blood platelets flowing in arterioles
Authors: Tangelder G. J. , Teirlinck H. C. , Slaaf D. W. , Reneman R. S.
Published: December 2017

The distribution of blood platelets flowing in arterioles (21-35 microns) of the mesentery of anesthetized rabbits was studied using intravital fluorescence microscopy. Sites were selected without upstream branch points within at least 10 vessel diameters. The distribution was determined by counting in flashed video frames the number of platelets present in each of six equal segments across the vessel. Only platelets were counted that could be localized objectively within a thin optical section around the median plane of the vessel. It could be shown that differences in counting volume between the six segments were negligible. Because of the use of flashed pictures (flash duration less than 0.1 ms; interval 180 ms), the method is independent of differences in velocity over the cross-sectional area of the vessel. In all measurements (15 sites in 13 vessels in 10 animals) the distribution was nonuniform, the wall segments containing the highest platelet numbers. The general distribution as calculated from all measurements (total platelet number 6,571) and expressed in percentages was found to be 23.0, 14.6, 12.5, 12.1, 13.6, and 24.2.
Negative chronotropic and parasympatholytic effects of alinidine on canine sinus node and AV junction
Authors: Hageman G. R. , Neely B. H. , Urthaler F. , James T. N.
Published: December 2017

The direct effects of alinidine (N-allyl-clonidine) on the sinus node and atrioventricular (AV) junction were studied in 18 anesthetized dogs. Stimulus frequency-response curves to right stellate ganglion and right cervical vagus stimulations as well as responses to norepinephrine or acetylcholine were determined before and after selective perfusion of alinidine into the sinus node artery. Alinidine (1 microgram/ml) had no effect on spontaneous sinus rate [148 +/- 5 (SE) beats/min]. However, alinidine concentrations of 5, 10, and 25 micrograms/ml produced significant (P less than 0.05) sinus slowing to 138, 127, and 121 beats/min, respectively. Recovery to control rate was dose dependent and took from 4 to 33 min. Sinus rate increases with right stellate stimulations were not affected by alinidine. However, sinus rate decreases with right vagal stimulations were significantly (P less than 0.01) attenuated by alinidine. The negative chronotropic effects of acetylcholine were not influenced by alinidine. Alinidine (1-100 micrograms/ml into AV node artery) had no effect on the A-H interval of the His bundle electrogram. However, alinidine (10 and 25 micrograms/ml) diminished the AV block produced by stimulation of the left vagus in electrically paced hearts but not the negative dromotropic actions of directly administered acetylcholine. Thus alinidine has direct negative chronotropic effects, no effect on sinus node responses to sympathetic stimulation, ability to diminish sinus node and AV junctional responses to vagal stimulations without interference at the cholinergic muscarinic receptor, and 4) no effect on AV nodal conduction.
Ca influx and sarcoplasmic reticulum Ca release in cardiac muscle activation during postrest recovery
Authors: Bers D. M.
Published: December 2017

The recovery of twitch tension (T) and Ca influx after 5-s to 10-min rest intervals was studied in rabbit, rat, and frog cardiac muscle. Extracellular double-barreled Ca-selective microelectrodes were used to assess transsarcolemmal Ca influx. In rabbit ventricle, T at the first postrest beat (B1) exceeded T at the second beat (B2). T and Ca influx then increase toward steady state in a parallel fashion. Since Ca influx is small at B1, this beat may be more dependent on Ca stored in the sarcoplasmic reticulum (SR), and subsequent beats may more closely reflect Ca influx. We have examined this hypothesis using agents that may preferentially inhibit either SR Ca release or Ca influx. SR inhibitors caffeine (5 mM) and ryanodine (100 nM) changed the pattern of T recovery so that B1 was now less than B2 and more closely paralleled the recovery of Ca influx. Caffeine and ryanodine decreased steady-state T to 89 +/- 9 and 78 +/- 3%, respectively. In contrast, B1 was found to be less susceptible to inhibition than B2 when exposed to La or Co (influx inhibitors). These results are consistent with a rabbit ventricle model in which the SR Ca release contributes greatly to B1, the SR contribution declines while the Ca influx component increases, and Ca influx at steady state can account for a large fraction of steady-state T. In adult rat ventricle, caffeine and ryanodine decrease steady-state T to 33 +/- 2 and 13 +/- 3%, respectively, changing the T recovery pattern from a monotonic decrease to a monotonic increase. These results are consistent with a model qualitatively the same as rabbit ventricle. However, the SR can account for most of steady-state T in the rat, and thus its decaying characteristic dominates the control postrest recovery. By inhibition of SR Ca release, the increasing component ascribed to Ca influx becomes apparent. Similar experiments were done to establish an order of relative dependence on SR Ca release: adult rat ventricle greater than rabbit atrium greater than rabbit ventricle greater than frog ventricle.
Dextran and capillary filtration coefficient in cat hindlimb
Authors: Watson P. D. , Wolf M. B.
Published: December 2017

To investigate the possible mechanisms through which dextran modifies capillary filtration coefficient (CFC), the effects of perfusion with a protein-free dextran solution were compared with those of perfusion with a Ringerlike solution. With the use of the isolated cat hindlimb, CFC was measured during perfusion at constant flow with three solutions, a control blood-albumin mixture, a Ringerlike solution called dialysate, and 3.7 g/dl dextran dissolved in dialysate. The solutions were warmed to 37-38 degrees C, bubbled with 95% O2-5% CO2, and contained 0.015 g/dl or more papaverine. CFC was calculated from the rate of limb weight gain following a step increase in venous pressure. Dextran perfusion increased CFC to 2.0 +/- 0.2 (SD, n = 8) times control, which was significantly less (P less than 0.001) than 3.1 +/- 0.6 (n = 8) times control previously reported for dialysate perfusion. The difference between the measured viscosity of dextran (1.35 cP) and dialysate (0.72) could account for this reduction. However, when a dialysate perfusion followed a dextran perfusion, CFC only increased to 2.3 +/- 0.4 (n = 8) times control. This value is also significantly less (P less than 0.01) than 3.1. This observation suggests 1) that dextran is retained within the transcapillary channel and 2) that dextran reduces CFC mainly by partially blocking the transcapillary channel rather than by increasing viscosity.
Coronary and systemic 6-ketoprostaglandin F1 alpha and thromboxane B2 during myocardial ischemia in dog
Authors: Prosdocimi M. , Finesso M. , Gorio A. , Languino L. R. , Del Maschio A. , Castagnoli M. N. , De Gaetano G. , Dejana E.
Published: December 2017

The left anterior descending coronary artery (LAD) of five dogs was ligated, and blood was withdrawn from the great cardiac vein, left marginal cardiac vein, femoral vein, and aorta. After ligation, immunoreactive 6-ketoprostaglandin (PG) F1 alpha rose from less than 0.1 to a mean value of 1.2 pmol/ml plasma in the great cardiac vein (GCV) and 0.88 pmol/ml in the left marginal vein, with no change in peripheral circulation. Immunoreactive thromboxane (TX) B2 remained below 0.075 pmol/ml throughout the experiments. LAD of 11 dogs was stenosed 60-80% with consequent cyclical reductions in blood flow. 6-Keto-PGF1 alpha in GCV rose in seven dogs (range 0.5-2.2 pmol/ml) and remained unchanged in four. No change was observed in peripheral plasma levels of 6-keto-PGF1 alpha. In these experimental conditions TXB2 remained below 0.075 pmol/ml. Lactate concentrations rose in both experimental conditions in GCV but not in peripheral circulation or in the left marginal vein. This study confirms a link between cardiac ischemia and increased coronary prostacyclin release, but we were unable to detect a similar correlation with TXB2 in plasma.
Model studies on distributions of blood cells at microvascular bifurcations
Authors: Chien S. , Tvetenstrand C. D. , Epstein M. A. , Schmid-Schonbein G. W.
Published: December 2017

To model the flow behavior of white and red blood cells at microvascular branch points, the distribution of neutrally buoyant spherical and disk-shaped particles at a symmetric T bifurcation was investigated for low Reynolds number flows (0.01-0.1). The particle distribution was represented by the fractional particle flux to a daughter branch as a function of the fractional volumetric bulk flow to the same branch. Particle-to-tube diameter ratios of 0.32-0.79 were studied for the spherical particles and 0.4-0.8 for the disks. As the particle dimensions approach that of the tube, the relation between the fractional particle flux and fractional bulk flow changes from a linear relation of unity slope to a nonlinear S-shaped curve. Measurements of the flow divider at the entrance to the bifurcation and the eccentricity distributions for the spheres and disks were used to develop a model that permits prediction of the observed particle distributions. These results can be used to interpret the distribution of white and red blood cells in microvascular bifurcations with dimensions close to the cell size.
Statistical constraints on microvascular measurements using fluorescent erythrocytes
Authors: Sarelius I. H. , McKinlay S. M.
Published: December 2017

We show that two separate estimators of microvessel hematocrit (H) using the same fluorescent cell technique are not equally precise. The precision of H (indicated by the coefficient of variation, CV) depends on in vivo labeled cell counts (m), the labeled fraction (p), and for time-averaged H estimates, the mean cell velocity (v). Thus, for length-dependent estimates of H, CV2(HL) = 1/E(m) + CV2(p) and for time-averaged H estimates, CV2(Ht) = 1/E(m) + CV2(p) + CV2(v). Because CV(p) can be made small arbitrarily and independently, the precision of H is principally dependent on the expected value of m. Practical sampling constraints and minimum sampling intervals are identified and used to define strategies to minimize CV(H). We show that Ht is preferable to HL because it is more precise and the useful in vivo sampling range of m and p is more flexible. In addition, Ht allows simultaneous determination of cell flux and mean cell velocity.
Enzymes and metabolites of glycogen metabolism in canine cardiac Purkinje fibers
Authors: Henry C. G. , Lowry O. H.
Published: December 2017

Canine Purkinje fibers were isolated by microdissection and analyzed for four enzymes of glycogen metabolism and eight related metabolites. Purkinje fiber glycogen levels were very high, confirming earlier reports. Glycogen synthesizing enzymes, glycogen synthase and UDP glucose pyrophosphorylase, were on the average 47 and 70% higher, respectively, in Purkinje fibers than in myocardium. Phosphorylase activity was approximately equal in the two tissue types, and phosphoglucomutase was 31% lower in Purkinje fibers. The metabolites of glycogen 6-phosphate were all higher in Purkinje fibers (P less than 0.001), but glucose 1,6-bisphosphate was lower by 50%. Phosphocreatine and ATP remained high in Purkinje fibers during 2 min of ischemia, while the phosphocreatine level in myocardium was falling by 75%. The results of this study suggest that the high glycogen synthetic capability, high precursor levels, and overall lower metabolic rate in Purkinje fibers compared with myocardium may explain the much higher glycogen levels.
Passive membrane properties of isolated feline ventricular myocytes
Authors: Houser S. R. , Bahinski A. , Silver L. H.
Published: December 2017

Membrane properties of adult mammalian cardiac muscle are difficult to define mainly because of experimental complications arising from complex packing of myocytes in the tissue matrix. Isolated feline myocytes were used in the present study to avoid these complications. The objectives of this study were to define the functional relationship between passive unidirectional transmembrane potassium (K+) fluxes, membrane permeability to K+ (PK), and membrane K+ (Ko) dependency of this relationship. Passive (ouabain-insensitive) components of unidirectional K+ fluxes were measured with 42K, and membrane potential (Em) and membrane (slope) conductance (gm) were measured with electrophysiological techniques. Myocytes studied in solutions with 5 mM K+o had normal resting potentials (-81 +/- 1 mV). The input resistance and membrane time constant were 2.72 +/- 0.47 X 10(-7) omega and 7.01 +/- 1.0 ms, respectively. When K+o was lowered Em hyperpolarized, input resistance (Ri) increased, and K+ fluxes decreased. When K+o was increased Em depolarized, Ri decreased, and K+ fluxes increased. These data were combined to determine whether K+ fluxes obey the independence principle and to calculate PK and gK. The results obtained support the idea that 1) unidirectional K+ fluxes do not obey the independence principle, 2) PK is much greater than the membrane permeability to other ions, and 3) the gK calculated from passive K+ fluxes was similar to the gm measured electrically (at all K+o's tested).
Arterial blood pressure control during hindlimb and forelimb contraction in the dog
Authors: Beaty O.
Published: December 2017

This study examined the differential reflex cardiovascular responses evoked by separate contractions of the right hindlimb and forelimb and established the mechanism of a regional reflex vasodilation associated with hindlimb skeletal muscle contraction. The two groups of skeletal muscle were contracted separately by electrical stimulation (2-48 Hz) of the peripheral motor nerves. The left nonexercising hindlimb was perfused at constant flow. All blood pressure-regulating mechanisms were intact. Arterial blood pressure (ABP), left nonexercising hindlimb perfusion pressure (HLPP), and heart rate (HR) were recorded. HR was increased by skeletal muscle contraction. This response was independent of muscle group and contraction frequency. Increases in both ABP and HLPP were produced by high-frequency contractions (greater than 16 Hz) of either the hindlimb or forelimb. Decreases were evoked only by hindlimb contractions (greater than 8 Hz). The nonexercising skeletal muscle vascular bed contributed to this systemic depressor response by vasodilating. The mechanism involved a contraction-induced withdrawal of sympathetic nerve activity to that vascular bed. Concomitant with this response was an increase in heart rate that was blocked with propranolol. Similar heart rate changes evoked by forelimb contractions also were blocked with propranolol. These data indicate that sympathetic outflow to resting skeletal muscle depends on the origin and magnitude of the afferent signal from the contracting skeletal muscle.
Permeability of blood-brain barrier to various sized molecules
Authors: Mayhan W. G. , Heistad D. D.
Published: December 2017

We studied disruption of the blood-brain barrier (BBB) by acute hypertension and a hyperosmolar solution. The goals were to determine whether 1) disruption of the BBB occurs primarily in arteries, capillaries, or veins, and 2) transport of different-sized molecules is homogeneous or size dependent. Sprague-Dawley rats were studied using intravital fluorescent microscopy of pial vessels and fluorescein-labeled dextrans (FITC-dextran, mol wt = 70,000, 20,000, and 4,000 daltons). The site of disruption was determined by the appearance of microvascular leaky sites. Transport of different-sized molecules was calculated from clearance of FITC-dextran. During gradual hypertension and osmotic disruption, all leaky sites were venular. Rapid hypertension produced venular leaky sites and, in some experiments, diffuse arteriolar extravasation of FITC-dextran. Clearance of different-sized molecules was homogeneous during acute hypertension. In contrast, clearance of molecules during osmotic disruption was size dependent. The findings suggest that 1) venules and veins are the primary sites of disruption following acute hypertension and a hyperosmolar solution; 2) transport of different-sized molecules is homogeneous following acute hypertension, which suggests a vesicular mechanism; and 3) transport following hyperosmolar disruption is size dependent, which suggests that hyperosmolar disruption may involve formation of pores as well as vesicular transport.
Altered myocardial mechanics in diabetic rabbits
Authors: Fein F. S. , Miller-Green B. , Sonnenblick E. H.
Published: December 2017

Diabetes mellitus may lead to congestive heart failure in humans, independent of atherosclerotic coronary artery disease. Previous studies have explored the myocardial effects of chronic diabetes in dogs and rats with somewhat divergent results. Therefore the current study examined papillary muscle function in rabbits made diabetic with 140-150 mg/kg intravenous alloxan compared with that of age-matched controls. The period of diabetes was 3 days (study 1), 1 mo (study 2), 3 mo (study 3), and 6 mo (study 4). The duration of isometric and isotonic contraction and relaxation were markedly prolonged in diabetes from studies 2, 3, and 4. Shortening velocity was diminished in diabetics from studies 1, 3, and 4. A blunted inotropic response to increasing stimulus frequency was observed in diabetics. Changes in resting tension were not consistently observed, suggesting that passive muscle stiffness is not altered. These findings indicate that previous work on diabetic rats can be extended to diabetic rabbits and suggest that chronic diabetes diminishes contractility and prolongs the duration of contraction in mammalian hearts.
Injection of guanosine 5'-cyclic monophosphate into heart cells blocks calcium slow channels
Authors: Bkaily G. , Sperelakis N.
Published: December 2017

The role of guanosine 5'-cyclic monophosphate (cGMP) in the regulation of the ionic slow channels in heart muscle is less well known than that of adenosine 3,'5'-cyclic monophosphate (cAMP). The effects of intracellular injection of cAMP and cGMP in cultured chick embryonic heart (ventricular) cells by the liposome method were studied. Injection of cAMP into the cells induced spontaneous slow action potentials that could be blocked by verapamil and nifedipine. Injection of cGMP blocked on-going slow action potentials, and this effect was reversed by increasing cAMP. Thus both cAMP and cGMP are involved in the regulation of the slow calcium channels in myocardial cells, and the two cyclic nucleotides are antagonistic.
Cell biology and protein composition of cardiac gap junctions
Authors: Manjunath C. K. , Page E.
Published: December 2017

The gap junctions that electrically couple mammalian myocardial cells have high (12,000–17,000/micron2)surface densities of channel-containing elements (connexons), undulating surfaces, and approximately hexagonally arrayed connexons disposed in small domains rotated with respect to one another. Optical diffraction combined with image processing of negatively stained isolated rabbit heart gap junctions shows six protein subunits surrounding the cell-to-cell channel and suggestive (but not conclusive) evidence for protein connections between connexons. Biochemical studies indicate that the six identical relative molecular weight (Mr) 47,000 subunits of mammalian cardiac gap junctions differ from liver gap junctions in the presence of a covalently bound Mr 17,500 cytoplasmic surface component that can be visualized electron microscopically in thin-sectioned and freeze-etched hearts. The cytoplasmic surface component is susceptible to cleavage by an alkaline serine protease released from mast cell granules by high ionic strength solutions (0.6 M KI) used to extract myofibrils during gap junction purification. Interlocking of connexons from coupled cells in the gap involves hydrogen bonding between protein subunits of the connexons.
Hepatic microcirculatory failure after ischemia and reperfusion: improvement with ATP-MgCl2 treatment
Authors: Clemens M. G. , McDonagh P. F. , Chaudry I. H. , Baue A. E.
Published: December 2017

Hepatic ischemia followed by reflow results in a myriad of metabolic and circulatory derangements that may eventually result in liver failure and death. In the present experiments we have used the technique of intravital fluorescence microscopy with fluoroscein isothiocyanate conjugated to bovine serum albumin as the intravascular fluorochrome to study the effects of ischemia and reperfusion on the hepatic microcirculation in vivo. Total hepatic ischemia was produced for 90 min to the left and median lobes of pentobarbital-anesthetized rats. After ischemia, reflow was allowed for 2 h. Three groups were studied: sham-ischemia controls and rats treated with either 1 ml saline or 12.5 mumol ATP-MgCl2 in 1-ml volume at the beginning of reflow. Although control rats exhibited stable microcirculation throughout the experiment, in saline-treated rats the number of perfused centrilobular areas and perfused sinusoids per unit area on the surface of the liver was decreased to approximately 50 and 40% of sham-ischemia controls, respectively. However, in rats treated with ATP-MgCl2 the density of perfused centrilobular areas and perfused sinusoids was 86 and 80% of sham-ischemia controls, respectively. From these results we conclude that intravital fluorescence microscopy is a potentially valuable method for the study of the hepatic microcirculation in vivo. Moreover, the results with ATP-MgCl2 treatment indicate that its effect on the microcirculation is a major factor in its beneficial effects on hepatic function after ischemia and reflow.
Cephalic carotid pressure as a measure of transmission through cervical ganglion
Authors: Tuttle R. S.
Published: December 2017

Cephalic or cranial pressure, i.e., pressure recorded craniad from the external carotid artery, was recorded in the cat during stimulation of the pre- and postganglionic trunks of the superior cervical ganglion (SCG) as was tension developed by the nictitating membrane under these situations. The influence of distension of the carotid sinus and of metoprolol on hemodynamic and tension responses was compared with control responses. Distension of the sinus with an indwelling balloon produced an increase of cephalic pressure evoked by stimulation of the SCG. Tension developed by the nictitating membrane was unaffected. Metoprolol reduced the increase in pressure resulting from stimulation of the preganglionic trunk of the SCG at 1.0 Hz but enhanced the pressure increase in the cranial circulation evoked by postganglionic stimulation of the SCG at 5.0 Hz. Action potentials, recorded postganglionically from the SCG, could be roughly grouped by height and latency into three populations. The height of the M3 population increased with distension of the carotid sinus. This study provides evidence that cephalic pressure can be used as a measure of the influence of various factors on the transmission of impulses through the SCG. This parameter appears to be a more sensitive measure of transmission than that of tension developed by the nictitating membrane. Distension of the carotid sinus is one factor that facilitates ganglionic transmission, whereas the beta-adrenoceptor antagonist metoprolol depresses it.
Diffusional support of arteries
Authors: Werber A. H. , Heistad D. D.
Published: December 2017

The relative role of the arterial lumen, adventitial vasa vasorum, and medial vasa vasorum in nutritional support of arteries is unclear. We have used a newly developed autoradiographic method to study diffusion of metabolically inert [14C]antipyrine into arteries to determine the relative importance of different pathways in nutritional support of arteries. [14C]antipyrine was homogenously distributed across the media of small arteries within 15 s, which indicates that diffusion into the central media was rapid. In the thoracic and abdominal aorta, levels of antipyrine were higher in the inner media (P less than 0.05) than in the middle of the media. Levels of antipyrine in outer media of the thoracic aorta (which has medial and adventitial vasa) were comparable to those observed in the inner media, but antipyrine levels were lower in outer than in inner media of the abdominal aorta (which has adventitial vasa only). Ligation of intercostal arteries, which are the source of medial vasa vasorum in the thoracic aorta, decreased diffusional support to the outer media of the thoracic aorta. We conclude that 1) diffusional support is more effective in thinner muscular arteries than in the aorta, 2) both luminal and abluminal sources of nutrition are important, particularly for the aorta, 3) vasa vasorum appear to be important for adequate diffusional support of the thoracic aortic media, and 4) medial vasa vasorum may be more effective than adventitial vasa vasorum in nourishing the aorta.
Anterior hypothalamic lesions impair reflex bradycardia selectively in rats
Authors: Miyajima E. , Bunag R. D.
Published: December 2017

To determine whether removal of the anterior hypothalamus would alter baroreflex activity, reflex inhibition of heart rate and renal nerve activity during pressor responses to intravenous phenylephrine was examined in rats with bilateral anterior hypothalamic lesions. Although there were no differences in basal blood pressure and heart rate 10 days after surgery, reflex bradycardia was significantly reduced in awake lesioned rats compared with sham-operated controls. The differences in reflex bradycardia were abolished by cholinergic blockade with atropine but unaltered by beta-adrenergic blockade with propranolol. Because attenuation of chronotropic reflexes by anterior hypothalamic lesions resembled that produced by cholinergic blockade, vagal inhibition must be at least partly responsible. Reflex bradycardia was still attenuated even in lesioned rats anesthetized with alpha-chloralose, but renal nerve activity was as inhibited as in sham-operated rats. These results suggest that the anterior hypothalamus participates in baroreflex regulation of heart rate by altering parasympathetic tone but without affecting cardiac or renal sympathetic nerve activity.
A comparison of ascorbate and glucose transport in the heart
Authors: Bassingthwaighte J. B. , Kuikka J. T. , Chan I. S. , Arts T. , Reneman R. S.
Published: December 2017

Multiple indicator-dilution experiments were done to compare the transcapillary exchange of tracer amounts of L-[14C]ascorbate and D-[3H]glucose (against an intravascular reference 131I-albumin) in Ringer-perfused (5 mM glucose) isolated rabbit hearts. The indicator-dilution curves for the two were virtually superimposed over the first 40-80 s. Estimates of the capillary permeability-surface area products, PSc, were the same, 2.3 +/- 0.7 (SD) ml X g-1 X min-1 (n = 18), in accord with the coincidence of their instantaneous extractions. The similarity of glucose and ascorbate permeabilities is explained by the similarity in molecular weights and passive diffusivity, their lipophobic nature, and the paucity of carrier-mediated endothelial transport for either molecule. The data were analyzed via a model composed of aggregates of spatially distributed capillary-tissue units (capillary blood, interstitium, myocytes) accounting for the heterogeneity of regional flows. The interstitial volumes in this preparation are enlarged, 0.30 +/- 0.04 ml/g. There is substantial entry into myocardial cells, the cell permeability-surface area products being approximately 2-3 ml X g-1 X min-1 for ascorbate and glucose. The estimated volumes of interstitial and intracellular space, 0.30 and 0.47 ml X g-1 X min-1, reflect interstitial edema and are very close to measured values, giving reassurance concerning the methods of modeling analysis.
Effect of prostaglandins on bradykinin-induced visceral-cardiac reflexes
Authors: Stebbins C. L. , Smith R. C. , Longhurst J. C.
Published: December 2017

We examined the effect of prostaglandins on the reflex cardiovascular response to bradykinin applied to the abdominal organs of anesthetized cats. Bradykinin (10 micrograms/ml) was applied to the serosal surface of the stomach, gallbladder, or jejunum before and after injection of indomethacin (2-10 micrograms/ml iv) and after application of 1 microgram/ml of prostaglandins E1, E2, or F2 alpha (PGE1, PGE2, PGF2 alpha) or prostacyclin (PGI2). In six cats, stimulation of the stomach with bradykinin significantly increased mean arterial pressure (MAP) by 37 +/- 5 (SE) mmHg and maximal dP/dt by 633 +/- 101 mmHg/s. Following indomethacin the bradykinin-induced increases in MAP and dP/dt were significantly reduced to 19 +/- 4 mmHg and 191 +/- 58 mmHg/s, respectively. Treatment with PGE1, PGE2, or PGI2, but not PGF2 alpha, restored the initial bradykinin response. The gallbladder and jejunum responded similarly. Also application of exogenous prostaglandins, PGE2 or PGI2, to the stomach, gallbladder, or jejunum significantly augmented the cardiovascular response to bradykinin. Finally, PGE2 restored a portion of the cardiovascular response to bradykinin following the development of tachyphylaxis. We conclude that prostaglandins are necessary for the full manifestation of the cardiovascular response to bradykinin.
Hemodynamic effects of arginine vasopressin in conscious water-deprived rats
Authors: Rascher W. , Meffle H. , Gross F.
Published: December 2017

By means of a specific antagonist [d(CH2)5AVP] of the vasoconstrictor activity of arginine vasopressin (AVP), we studied whether the vasoconstrictor effect of AVP contributed to the blood pressure control during water deprivation in conscious rats. After 24 h of dehydration plasma AVP rose from 3.5 +/- 0.5 to 11.2 +/- 2.0 fmol/ml. Intravenous injection of 5 micrograms/kg d(CH2)5AVP reduced total peripheral resistance. Since cardiac output rose simultaneously, mean arterial blood pressure remained unchanged. In rats with sinoaortic deafferentation (SAD) 4 wk before water deprivation, d(CH2)5AVP caused a reduction of total peripheral resistance and of mean arterial pressure, whereas cardiac output remained unchanged. Consequently, mean arterial pressure fell. No hemodynamic changes were observed in hydrated control rats with and without SAD. It is concluded that the vasoconstrictor activity of AVP plays an important role in maintaining blood pressure during water deprivation in conscious rats. After AVP blockade, arterial pressure fell only in SAD rats as intact rats maintain arterial pressure via acute increase cardiac output.
Evidence against role of antidiuretic hormone in support of blood pressure during dehydration
Authors: Fejes-Toth G. , Naray-Fejes-Toth A. , Ratge D.
Published: December 2017

The contribution of arginine vasopressin (AVP) to the maintenance of mean arterial pressure (MAP) during fluid deprivation was reinvestigated in chronically prepared, conscious, freely moving rats. In normal Long-Evans (LE) rats during water deprivation for up to 48 h plasma AVP levels increased from 2.98 +/- 0.62 to 17.55 +/- 2.03 pg/ml, but MAP and heart rate (HR) remained unchanged. Fluid deprivation for 10 h in Brattleboro homozygous rats that are unable to synthetize vasopressin resulted in a more severe water depletion than 48 h of dehydration in the normal rats, but also in this group MAP and HR were maintained at values not significantly different from control. Cardiac output (CO) fell during the course of dehydration in both LE and Brattleboro rats. Injection of 20 micrograms/kg of the vasopressin pressor antagonist, 1-deamino-penicillamine, 2-(O-methyl)-tyrosine AVP [dPTyr(Me)AVP] did not decrease MAP or increase HR in LE rats after 24 h of water deprivation and was ineffective even after 48 h of fluid deprivation. CO also remained unchanged following AVP blockade. Efficacy of the antagonist was verified by complete inhibition of the pressor response elicited by exogenous AVP. The concentration of plasma catecholamines was unaltered by dPTyr(Me)AVP. Blockade of the renin-angiotensin system via converting-enzyme inhibition failed to reveal any depressor effect after injection of dPTyr(Me)AVP. Thus it appears that AVP is not involved in the maintenance of blood pressure after fluid deprivation in conscious rats.