bluuebunny/crossref_metadata_2025 huggingface dataset:
Peripheral resistance after cardiac output reduction in the barodenervated cat.
Authors: Borgdorff P
Published: June 2012

Studies on the nervous or humoral control of total peripheral resistance are often complicated by concomitant changes in cardiac output. We studied the influence of cardiac output on peripheral resistance in the absence of modulating reflexes. In barodenervated and vagotomized cats, cardiac output was varied by graded inferior caval vein occlusion or by arterial bleeding. Total peripheral resistance was obtained with an analogue device which continuously divided the pressure difference between aorta and caval vein by cardiac output (electromagnetic flowmeter). Cardiac output reduction caused a decrease of peripheral resistance, followed within 2 minutes by a slow increase. Resistance stabilized at preocclusion levels within 5.8 (range 4-9) minutes. The relative changes in resistance and cardiac output were linearly related, when cardiac output was reduced by less than 40%. With larger reductions, the relation became nonlinear, and with a drop of more than 65%, no further change was noticed. These changes in resistance could not be explained by variations in blood viscosity as measured by Hct. They were nonnervous in nature: when all reflexes were abolished by ganglionic blockade, a similar pattern was found. Humoral mechanisms like the vasopressin or the renin-angiotensin system, known to be activated by hypotension, probably played no role, since arterial osmolality remained stable and captopril did not influence the resistance response. The involvement of metabolic autoregulation could not be excluded, but was unlikely because O2 consumption and serum lactate did not change.
Pressure gradient related to energy conversion in the aorta.
Authors: Melbin J , Noordergraaf A
Published: June 2012

In this study, we analyzed a common form of experimental investigation of blood vessels, in which measurements are obtained with branches ligated. Utilizing representative pressure and flow pulses and the full expression for the equation of motion, we calculated the axial pressure gradient, in the time domain at a plane in the descending aorta. The time function representing the ratio between axial pressure gradient and axial flow for the resulting tapering geometry was subjected to Fourier analysis. The harmonics were utilized to obtain the real and imaginary components of the longitudinal impedance as if it were a linear system. In a linear system, the real and imaginary components represent the viscous and inertial properties of the fluid, respectively. For the system studied, however, the real part contained both viscous and substantial in-phase components arising from the inertial terms of the equation of motion. The real part, therefore, cannot be interpreted as indicative solely of dissipated energy. When measurements are obtained from an adulterated system, caution must be exercised if the interpretation is to be considered that of the real system. The analysis clarifies an anomalous issue concerning resistive features of the aorta.
Distribution of myosin isozymes within single cardiac cells. An immunohistochemical study.
Authors: Samuel J L , Rappaport L , Mercadier J J , Lompre A M , Sartore S , Triban C , Schiaffino S , Schwartz K
Published: June 2012

Isozymes of myosin have been localized with respect to individual cardiac myocytes in hearts from 3-week-old, adult controls, and adult hypophysectomized rats, and in cultured cardiac cells. For this purpose, affinity-purified antibodies reacting specifically with the heavy chains of each of the two major myosin isozymes of adult rat heart, V1 and V3, were used. The distribution of the two isomyosins was determined by double immuno-labeling of the same cell, V1 myosins being revealed by rhodamine and V3 myosins by fluorescein. A procedure is described which allows optimum immunological visualization of the myosin filaments of rod-shaped isolated myocytes. It was found that the response of the cardiac cells to the two antimyosins varied depending on the state of the animal. In 3-week-old rats, all cells were stained with the anti-V1, and almost none with the anti-V3 myosin. In the hypophysectomized animals, on the contrary, all cells were stained with the anti-V3 and none with the anti-V1. A mixed pattern of reactivity was observed in adult controls since 50% of the cells reacted with the anti-V1, 10% with the anti-V3, and 40% with both antibodies. In the latter case, the distributions of V1 and V3 reactivities were homogeneous throughout the cell, and absolutely superimposable. The same double reactivity and homogeneous repartition were observed in cultured cells. These findings indicate that myocytes from adult rat myocardium are heterogeneous in terms of their isomyosins content and show for the first time that two isomyosins can coexist and be equally distributed in one cardiac cell. These observations are relevant to the regulation of individual heart cell contractility.
Relationship between myocardial oxygen consumption, coronary flow, and adenosine release in an improved isolated working heart preparation of guinea pigs.
Authors: Bardenheuer H , Schrader J
Published: June 2012

We describe herein an isolated working heart preparation of guinea pigs, in which coronary perfusion pressure can be varied independently from afterload by directing left ventricular stroke volume into an artificial circulation. This preparation proved to be functionally stable, exhibited hemodynamic features characteristic of the heart in situ, and shows the phenomena of flow autoregulation, reactive hyperemia, and hypoxic and metabolic vasodilation. Myocardial oxygen consumption and coronary flow were tightly coupled when cardiac work was enhanced by either 1.5-6.0 X 10(-9) M isoproterenol (r = 0.975) or changes of afterload (20-100 mm Hg) (r = 0.890). Isoproterenol-induced changes in adenosine release correlated with changes of coronary flow (r = 0.869) and myocardial oxygen consumption (r = 0.894). The concentrations of endogenously formed adenosine were within the vasodilatory range of exogenously applied adenosine. In contrast, afterload-induced changes in myocardial oxygen consumption were not associated with an enhanced release of adenosine, inosine, and hypoxanthine, and did not correlate with coronary resistance (r = 0.422). The specific activity in the effluent perfusate of intracoronarily infused [8-14C]adenosine was increased with elevated afterload, suggesting that less adenosine was liberated by the heart. Our findings indicate that adenosine formed in response to beta-adrenergic stimulation is a major metabolite adjusting coronary flow to myocardial needs. Adenosine, however, does not appear to be involved in the afterload-induced changes in coronary flow when coronary perfusion pressure and, thus, oxygen supply are increased simultaneously. It is likely that formation of adenosine is not triggered by changes in MVO2 as such, but may critically depend on the oxygen supply: demand ratio.
Thyroxine-induced hypertrophy of the rabbit heart. Effect on regional oxygen extraction, flow, and oxygen consumption.
Authors: Talafih K , Briden K L , Weiss H R
Published: June 2012

The effects of the administration of 0.5 or 1 mg/kg of 1-thyroxine for 3 or 16 days were studied in 55 New Zealand white rabbits. Heart size was 29% above control after 16 days of 1-thyroxine, despite lower body weights. In an anesthetized open-chest animal, regional microspectro-photometric observations of small arteries and veins to determine oxygen extraction were combined with regional blood flow measurements using radioactive microspheres to determine regional oxygen consumption by the Fick principle. Vascular flow reserves were studied through measurement of blood flow after the administration of chromonar HCl, 10 mg/kg. Myocardial oxygen consumption was, respectively, 2.4 and 3.8 times control after 3 and 16 days of 1-thyroxine. This was accompanied by significant increases in both coronary blood flow and oxygen extraction. In control, oxygen extraction and consumption were higher in the subendocardial region compared to the subepicardial area. No significant regional differences were found in flow, oxygen extraction, or consumption after 1-thyroxine administration. Chromonar increased coronary blood flow 2.8 times in the control animals, but did not significantly increase flow or decrease vascular resistance in the rabbits given 1-thyroxine. Adenosine increased coronary blood flow 3.5 times in the control animals but only 2.2 times in animals given 1-thyroxine for 3 days. Animals given 1-thyroxine had hypertrophied hearts with increased oxygen consumption, markedly increased flow, and increased oxygen extraction but without regional left ventricular differences.
Agonist-induced endothelium-dependent relaxation in rat thoracic aorta may be mediated through cGMP.
Authors: Rapoport R M , Murad F
Published: June 2012

The present study investigates the hypothesis that endothelium-dependent relaxation of vascular smooth muscle may be mediated through the formation of cGMP. Relaxation of the rat thoracic aorta to acetylcholine, histamine, and Ca++ ionophore A23187 was associated with increased levels of cGMP in a time- and concentration-dependent manner, whereas cAMP levels were unaltered. Removal of the endothelium prevented relaxation to these agents and prevented the increased levels of cGMP. Removal of the endothelium after exposure to acetylcholine only partially decreased the elevated levels of cGMP, suggesting that the changes in cGMP occurred within the smooth muscle cells. Eicosatetraynoic acid, an inhibitor of lipoxygenase and cyclooxygenase, and quinacrine, an inhibitor of phospholipase, prevented and reversed acetylcholine-induced relaxation, respectively, and inhibited acetylcholine-induced increased levels of cGMP. In contrast, sodium nitroprusside-induced relaxation and increased levels of cGMP were independent of the presence of the endothelium, exposure to eicosatetraynoic acid, and quinacrine. The present results support the hypothesis that vascular smooth muscle relaxation induced by some agents is dependent on the presence of the endothelium and is mediated through the formation of an endothelial factor that increases cGMP levels in smooth muscle.
Carotid sinus baroreceptor activity in the nonhuman primate.
Authors: Tomomatsu E , Huffman L , Gilmore J P
Published: June 2012

The carotid sinus of eight adult Macaca fascicularis monkeys was functionally isolated from the circulation and perfused with Krebs-Henseleit solution. The impulse activity in 65 carotid sinus baroreceptor fibers from the left carotid sinus nerve was studied during nonpulsatile perfusion and was compared with the impulse activity in 68 fibers from 10 adult mongrel dogs. Curves relating the discharge frequency to carotid sinus pressure were constructed. The baroreceptor fibers of the monkey had a significantly lower threshold, gain, pressure at the point of inflection, and plateau pressure than those of the dog. Hysteresis, as indicated by the separation of the stimulus-response curves obtained by increasing and then decreasing carotid sinus pressure, was observed. At any given pressure, the discharge frequency of baroreceptors was greater when carotid sinus pressure was increased than when it was decreased in both species. These results provide direct evidence that carotid sinus baroreceptors in the monkey are less sensitive to pressure changes than those in the dog.
Facial vein of the rabbit. Intracellularly recorded hyperpolarization of smooth muscle cells induced by beta-adrenergic receptor stimulation.
Authors: Prehn J L , Bevan J A
Published: June 2012

A segment of the facial vein of the rabbit gains myogenic tone when placed under tension in a tissue bath (Winquist and Bevan, 1977); low frequency electrical stimulation of intramural nerves, or application of norepinephrine or isoproterenol produces relaxation, which is blocked by propranolol (1.0 microM). We measured membrane potential of single smooth muscle cells with microelectrodes during this beta-adrenergic receptor-mediated relaxation of the vein segment. Hyperpolarization (up to 30 mV) invariably accompanied relaxation. Average maximum resting potential recorded in normal Krebs solution was -46.8 +/- 3.6 mV (mean +/- SE); this increased to -70.8 +/- 3.0 mV when high concentrations (greater than 10 nM) of isoproterenol were added to the bath. Tone and membrane potential were very sensitive to intramural nerve stimulation. At 3-4 Hz, relaxation was about half maximal and hyperpolarization was 6-9 mV. The maximum hyperpolarization to nerve stimulation was 20-30 mV, about the same magnitude as that produced by isoproterenol. Hyperpolarization clearly preceded relaxation by about 0.2 second. The magnitude of hyperpolarization in facial vein is much larger (2-10 times or more) than that recorded in other tissues during inhibition produced by stimulation of beta-adrenergic receptors. The large hyperpolarization may augment the effectiveness of inhibition (by curtailing potential dependent influx of Ca++o, for example) in this tissue compared to that in other tissues in which hyperpolarization is slight or absent. The ionic mechanism underlying hyperpolarization resulting from stimulation of beta-adrenergic receptors remains unclear.
Role of hydrostatic and oncotic pressures in renal sodium reabsorption.
Authors: Knox F G , Mertz J I , Burnett J C , Haramati A
Published: June 2012

Physical factors, and renal interstitial hydrostatic pressure in particular, have an important effect on sodium excretion by the kidney. Changes in hydrostatic and oncotic pressures in the peritubular microcirculation may have effects on proximal tubule reabsorption under some, but not all, circumstances. In regard to control of sodium excretion, the loop of Henle may be a particularly important segment which is sensitive to transepithelial hydrostatic pressure changes. There is little evidence to support an effect of physical factors on sodium reabsorption by the distal tubule. The collecting tubule may be another pressure-sensitive site; however, changes in sodium reabsorption by deep nephrons in the kidney may account for changes that have been attributed to the collecting duct. Changes in intrarenal pressure may be an important link in the regulation of sodium excretion, particularly in pathological circumstances, such as the exaggerated natriuresis of hypertension and the sodium retention seen in congestive heart failure.
Attenuation of the negative chronotropic effect of myelinated fibers by nonmyelinated fibers in the vagus nerve of the rabbit.
Authors: de Neef K J , Jansen J R , Versprille A
Published: June 2012

In the adult rabbit, both myelinated and nonmyelinated efferent fibers travel from the cervical vagus nerve to the sinoauricular node. The myelinated fibers convey the negative chronotropic effect. The influence of the nonmyelinated fibers was studied. Stimulation (4/sec) of the myelinated fibers, while the compound action potential was monitored continuously, caused a slowing of the heart rate. Subsequent activation of the non-myelinated fibers attenuated this negative chronotropic effect. Stimulation of adrenergic fibers was excluded, based on data from histochemical studies and the effects of blockade of beta- and muscarinic receptors. The lengthening of the RR interval during activation of the myelinated fibers alone was about 3.5 times larger than during activation of all fiber groups. When the conduction of the myelinated fibers was blocked (anodal block), activation of the nonmyelinated fibers did not show any effect on heart rate. It was concluded that the negative chronotropic effect is conducted via small myelinated fibers and that the nonmyelinated fibers modulate the effect of these cardiomotor fibers, without having an effect on heart rate on their own. This modulation is effected either via a presynaptic mechanism on preganglionic fibers or via an interaction with postganglionic neurons. The nonmyelinated fibers constitute a novel peripheral system to modulate heart rate.
Determinants of a protective effect of glucose and insulin on the ischemic myocardium. Effects on contractile function, diastolic compliance, metabolism, and ultrastructure during ischemia and reperfusion.
Authors: Apstein C S , Gravino F N , Haudenschild C C
Published: June 2012

The efficacy of hyperglycemia and insulin therapy for reducing ischemic myocardial injury is controversial and unproven. Accordingly, factors that might influence the effects of hyperglycemia and insulin were studied in isolated perfused rabbit hearts at two degrees of global ischemia, either "severe" or "moderate." During the ischemic period, different groups (n = 15-28/group) received either 100 mg/100 ml glucose-no insulin (control group), 500 mg/100 ml glucose + 100 mU/ml insulin (G + I), or 100 mg/100 ml glucose + 400 mg/100 ml mannitol (osmotic control). During moderate ischemia, effective washout of myocardial lactate was maintained, and hyperglycemia and insulin doubled the glycolytic flux, completely prevented contracture during ischemia, decreased contracture during reperfusion, increased recovery of postischemic contractile function, decreased ultrastructural damage, and increased high energy phosphate levels. Hyperglycemia and insulin increased glycolytic flux only after 30 minutes of ischemia had elapsed, suggesting that endogenous glycogen provided adequate glycolytic substrate prior to this time. The mannitol-glucose substrate had no beneficial effects, indicating that the hyperglycemia and insulin substrate had a metabolic rather than an osmotic mechanism of action. In contrast, during severe ischemia, tissue lactate washout was ineffective; the hyperglycemia and insulin substrate increased glycolytic flux by only 15% and produced no persistent beneficial effects. These results suggest that hyperglycemia and insulin therapy is beneficial to the ischemic myocardium when two conditions are met. First, the degree of myocardial perfusion, although in the ischemic range, must be adequate to prevent the accumulation of high tissue levels of lactate which inhibit glycolysis and prevent any glycolytic stimulation by hyperglycemia and insulin. Second, the ischemic myocardium must be "glucose dependent" for glycolytic substrate; in our studies this occurred after 30-45 minutes of sustained ischemia, probably because myocardial glycogen stores became depleted.
Phasic effects of repetitive vagal stimulation on atrial contraction.
Authors: Martin P J , Levy J R , Wexberg S , Levy M N
Published: June 2012

The vagus nerves of anesthetized dogs were stimulated once each cardiac cycle with a brief burst of pulses, and the timing of the stimulus bursts was changed by a fixed increment on successive cardiac cycles. The effects of such vagal stimulation on atrial contraction depended on the number of pulses per stimulus burst, on the interval between pulses within the burst, and on the timing of the stimulus bursts within the cardiac cycle. The vagal stimulus bursts had the least negative inotropic effect when they were given less than 100 msec before the next atrial depolarization, and they were most effective when given about 330 msec before the next atrial depolarization. This dependence of the inotropic response on the timing of the vagal activity within the cardiac cycle indicates that the following conditions must prevail with respect to the vagal innervation of the atrium: (1) the acetylcholine released from the vagal nerve endings is hydrolyzed at a critically rapid rate in the atrial tissues, (2) the neurally released acetylcholine must exert its major influence on atrial contraction during some preferential fraction of the cardiac cycle (presumably, during depolarization), and (3) after a vagal stimulus of a given strength, the concentration of acetylcholine in the region of the myocardial cells will attain its maximum value during this critical phase of the cardiac cycle when the vagal stimuli are given at the optimal time in the cardiac cycle.
Metabolism of circulating adenosine by the porcine isolated perfused lung.
Authors: Hellewell P G , Pearson J D
Published: June 2012

Adenosine uptake was studied in the piglet isolated perfused lung by means of the single-circulation paired-tracer dilution technique. Adenosine was efficiently taken up from the pulmonary vascular bed, and the process was potently inhibited by dipyridamole. Following uptake, adenosine was incorporated into intracellular nucleotides, and at low perfusate concentrations, little or none of the incorporated radioactivity returned to the circulation. At higher concentrations, cellular uptake was saturable and products of intracellular catabolism (inosine and hypoxanthine) were returned to the circulation. Perfusion of low concentrations of adenosine after inhibition of pulmonary adenosine kinase led to a proportional decrease in the retention of nucleotides and to a release of inosine and hypoxanthine. A small proportion of adenosine was metabolised extracellularly by adenosine deaminase; this activity was not released from perfused lungs and is apparently an ecto-enzyme.
Renal responses of the cardiac-denervated nonhuman primate to blood volume expansion.
Authors: Peterson T V , Jones C E
Published: June 2012

Experiments were performed to determine whether total, specific cardiac denervation affects the renal responses of the nonhuman primate to acute intravascular volume expansion. Adult male Macaca fascicularis monkeys underwent chronic intrapericardial cardiac denervation or sham surgery. After a 14- to 30-day recovery period, each animal was anesthetized with sodium pentobarbital and estimated blood volume was volume-expanded 20% with 6% dextran in isotonic saline. Control renal excretory function did not differ between the two groups, and both groups had similar increases in urine flow, sodium and potassium excretion, osmolar clearance, free water clearance, and renal plasma flow after volume expansion. The times to peak diuresis and natriuresis also were similar in both groups. These results demonstrate that the cardiac-denervated monkey shows unattenuated renal excretory responses to volume expansion. This could indicate that either cardiac receptors do not play a major role in eliciting these responses in the primate or that eliminating a role of cardiac afferents is compensated for by redundant afferents from arterial baroreceptors.
The dependence of unloaded shortening velocity on Ca++, calmodulin, and duration of contraction in "chemically skinned" smooth muscle.
Authors: Paul R J , Doerman G , Zeugner C , Rüegg J C
Published: June 2012

Unloaded shortening velocity, a mechanical parameter associated with the rate of cross-bridge cycling, was investigated in chemically skinned guinea pig taenia coli and hog carotid artery. Shortening velocity was measured by the technique described by Edman, whereby large length steps are rapidly imposed on the muscle and the time under unloaded conditions is determined from the isometric myograms. Shortening velocity determined in this manner was similar to Vmax from the Hill force-velocity relations reported for both living and skinned taenia coli, and, in the case of carotid artery, was at least as large as that reported for living muscle. The behavior of shortening velocity was qualitatively similar for both preparations. Shortening velocity was strongly temperature dependent, with a Q10 of approximately 3.6. Shortening velocity was found to be dependent on both the Ca++ and calmodulin concentration. In contrast to the dependence of isometric force on Ca++-calmodulin, shortening velocity could be increased further by the addition of Ca++ and/or calmodulin under conditions when isometric force was maximized. Incubation with ATP-gamma S, which presumably maximizes the phosphorylation of myosin, did not increase shortening velocity beyond the maximum value obtained in the presence of Ca++-calmodulin alone. The development of shortening velocity after exposure to high Ca++ solution was found to precede that of isometric force. The steady state value tended to be slightly lower than the maximum shortening velocity, the largest difference observed being less than 1.5-fold. Thus, whereas both isometric force and shortening velocity are dependent on the Ca++-calmodulin concentration in skinned smooth muscle, the dependencies are not identical, differing with respect to temporal development and concentration. These differences may underlie the decline in velocity with maintained isometric force observed in living smooth muscle.
Natriuretic activity of human and monkey atria.
Authors: Nemeh M N , Gilmore J P
Published: June 2012

Recent evidence indicates that mammalian atria contain a substance that produces a rapid onset natriuresis in anesthetized rats. In the present experiments, small portions of human right atria obtained from patients undergoing coronary bypass surgery, as well as monkey atria and ventricles obtained from the Regional Primate Center, Seattle, were boiled or acid extracted and lyophilized. These materials (30 mg/kg) were dissolved in Ringer's lactate and injected intravenously into anesthetized monkeys to determine their effects on renal function. Their effects were also compared with those of furosemide (0.1 mg/kg) and chlorothiazide (10 mg/kg). Human and monkey atrial extracts produced significant increases in sodium and calcium excretion that were independent of changes in creatinine clearance. Monkey ventricular extract had no consistent renal effects. Furosemide, but not chlorothiazide, mimicked the renal responses to human and monkey atrial extracts in terms of time of onset, duration, and pattern of electrolyte excretion. These data suggest that primate atrial tissue contains a heat- and acid-stable natriuretic factor similar to that first described in the rat, suggesting that mammalian atrial natriuretic factors are cross-reactive among species. In addition, atrial natriuretic factors may have a mechanism of action similar to that of furosemide.
Age-associated alterations in viscoelastic properties of canine aortic strips.
Authors: Yin F C , Spurgeon H A , Kallman C H
Published: June 2012

Many studies have delineated the changes in the elastic properties of arterial tissue as a function of age. Despite the fact that viscoelasticity is a prominent feature of these tissues, there is little information or characterization of age-associated changes in viscoelastic properties, over a wide range of smooth muscle activation, particularly in nonhuman tissue where atherosclerosis is not a confounding factor. In the present study, using small sinusoidal length perturbations, we determined the dynamic stiffness properties across a wide range of lengths (stretch ratios from 100 to 135%) and frequencies (from 0.25 to 35 Hz) in strips excised from ascending and descending aortas from six young (2 to 4-year-old) and 12 senescent (10- to 13-year-old) beagles. Studies were performed with the smooth muscle fully activated with calcium and norepinephrine, as well as fully inactivated with cyanide, iodoacetate, and dinitrophenol. There was a cubic nonlinear dependence of stiffness modulus on length only in senescent tissue and, surprisingly, little frequency dependence in tissue of either age. Compared to the young aortas, the three-dimensional surface representing the dependence of stiffness modulus on length and frequency from both the ascending and descending regions of aged aortas was displaced higher on the stiffness axis both with the muscle fully activated and inactivated. This age difference was accentuated at longer lengths. The phase lag between force and length was greater in the young vs. the old strips only in the activated, ascending aortic tissue. We found no age differences in the content of elastin, collagen, or in the collagen/elastin ratio, to account for these mechanical property differences.(ABSTRACT TRUNCATED AT 250 WORDS)
Vascular smooth muscle cell hypertrophy and hyperploidy in the Goldblatt hypertensive rat.
Authors: Owens G K , Schwartz S M
Published: June 2012

Our major objective in this study was to examine the hypothesis that the aortic smooth muscle cell hypertrophy and hyperploidy observed in previous studies of spontaneously hypertensive rats is not peculiar to that model, but also occurs in Sprague-Dawley rats made hypertensive by a Goldblatt procedure (two-kidney, one-clip model). Flow microfluorometric and microdensitometric analysis of smooth muscle cell DNA content showed a significant increase in the frequency of tetraploid smooth muscle cells from 5.6 +/- 0.9% in controls to 14.6 +/- 1.94% in hypertensives 1 month after Goldblatt surgery. Neither differences in ploidy nor elevation in blood pressure were apparent 2 weeks after surgery. The frequency of polyploid smooth muscle cells increased with age, duration of hypertension, and level of blood pressure. Analysis of the interrelationship between smooth muscle cell ploidy and hypertrophy in 5-month post-surgery Goldblatts by cytospectrophotometric measurements of the protein and DNA content of individual smooth muscle cells showed that tetraploid and octaploid cells from Goldblatt rats had 64% and 129% greater protein mass, respectively, than diploid cells. In addition, the mean protein mass of smooth muscle cells from Goldblatts was approximately 100% greater than that of normotensive controls, with each of the ploidy classes in Goldblatts having a higher frequency and mass than the corresponding cells in controls. Estimates of cell number per centimeter aortic length, based on measurements of average DNA/cell and total aortic medial DNA, showed no difference between hypertensives and controls. Furthermore, the rate of accumulation of polyploid cells could account for the increased frequency of cells undergoing DNA synthesis as measured by [3H]thymidine autoradiography. Thus, smooth muscle cell hypertrophy, not hyperplasia, was responsible for the increased mass of smooth muscle in aortas of Goldblatt hypertensive rats compared with normotensive controls, and this smooth muscle cell hypertrophy was accompanied by an increase in DNA ploidy.
Propagation through electrically coupled cells. Effects of regional changes in membrane properties.
Authors: Joyner R W , Picone J , Veenstra R , Rawling D
Published: June 2012

The normal process of excitation of the heart involves propagation of action potentials through cardiac regions of different anatomy and different intrinsic membrane properties. Although our understanding of these properties is still incomplete, it is well accepted that the parameters measured from a single cell penetration in an electrical syncytium (e.g., action potential duration, rate of rise, and velocity) reflect not only the properties of that cell but also the electrotonic interactions with other cells to which the recorded cell is electrically coupled. We have used simulation techniques to predict the spatial distribution of action potential parameters resulting from discretely localized alterations in the intrinsic membrane properties of some of the cells of an electrical syncytium. We have shown that the resulting spatial distribution is markedly different for alterations in plateau and pacemaker currents vs. rising phase currents, and that other factors, such as the site of stimulation and the underlying spatial pattern of cell-cell coupling resistance, also modify the spatial distribution of action potential properties resulting from a discrete regional change in intrinsic membrane properties.
Vagal afferent inhibition of spinothalamic cell responses to sympathetic afferents and bradykinin in the monkey.
Authors: Ammons W S , Blair R W , Foreman R D
Published: June 2012

Effects of stimulating the left thoracic vagus nerve on the responses of spinothalamic neurons to electrical stimulation of cardiopulmonary sympathetic afferent fibers and to intracardiac injections of bradykinin were determined. Experiments were performed on 39 monkeys (Macaca fascicularis) tranquilized with ketamine and anesthetized with alpha-chloralose. The 30 spinothalamic cells studied had the following characteristics. They were excited by manipulation of their somatic receptive fields, were excited by electrical stimulation of cardiopulmonary sympathetic afferent fibers, and exhibited viscerosomatic convergence. Responses of 15 of 19 cells to sympathetic afferent test stimuli were inhibited by conditioning stimuli applied to left thoracic vagus nerve. A conditioning-test interval of 40-50 msec resulted in maximal inhibition of responses to both A delta and C fiber sympathetic afferents. A long time course of inhibition was present to at least a conditioning-test interval of 200 msec. Left thoracic vagus nerve stimulation inhibited 14 of 14 cells responding to intracardiac injection of bradykinin. Entrainment of activity of five cells to the cardiac cycle occurred in response to bradykinin. In each case, left thoracic vagus nerve stimulation, in addition to reducing frequency of cell discharge, disrupted the cardiac related pattern of cell activity. Bilateral cervical vagotomy abolished all inhibitory effects of left thoracic vagus nerve stimulation. These results demonstrate that vagal afferents may participate in processing of information related to cardiac pain.
Activation of contraction and ATPase activity in intact and chemically skinned smooth muscle of rat portal vein. Dependence on Ca++ and muscle length.
Authors: Arner A , Hellstrand P
Published: June 2012

The mechanical manifestations of muscle contraction (force development or shortening) are accompanied by an increased turnover of chemical energy (ATPase activity, JATP). In intact rat portal veins activated by high potassium medium to produce graded contractions at different levels of extracellular calcium, a linear dependence of oxygen consumption on force was found. The slope of the relation (metabolic tension cost) was higher during early stages than during late stages of contraction, possibly reflecting a transient high crossbridge ATP turnover rate. Chemically skinned (Triton X-100) rat portal vein preparations were used to study the energy turnover of the smooth muscle contractile system under constant activation. In these preparations, JATP increased on activation by calcium in the presence of 1 microM calmodulin, remained constant for maintained contractures, and decreased promptly on relaxation. Force declined with each repeated contraction at optimal calcium level (10(-4.5) M), but the relation between force and JATP remained invariant and agreed with that of the intact muscle during the transient of high ATP turnover. Calcium activation in the range 10(-9) to 10(-4.5) M caused a progressively steeper (nonlinear) increase in JATP with force. Length-force relations showed a lower relative force at muscle lengths below L0 in the intact than in the skinned tissue, possibly indicating depression of excitation-contraction coupling. The slope of the relation between JATP and force was lower when length was varied than when calcium was varied. At a length where no external force was produced, the activated muscle had a significantly higher JATP than while relaxed (10(-9) M Ca++).(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of sulfinpyrazone on homocysteine-induced endothelial injury and arteriosclerosis in baboons.
Authors: Harker L A , Harlan J M , Ross R
Published: June 2012

The effect of sulfinpyrazone on endothelial injury induced by homocysteine has been studied both in vitro, using cultured human umbilical vein endothelial cells, and in vivo, using a primate model of homocysteine-induced arteriosclerosis. Oral sulfinpyrazone (250 mumol/kg body weight per day in three divided doses) in eight chronically homocystinemic baboons (0.14 +/- 0.04 mM plasma homocystine) decreased the extent of aortic endothelial injury as measured morphometrically by silver staining techniques, compared with six untreated comparably homocystinemic animals (denuded surface averaged 0.5% with range 0-2.1 vs 7.7 +/- 1.6%, respectively; P less than 0.001). Sulfinpyrazone therapy to homocystinemic baboons also normalized platelet survival and turnover measurements (5.1 +/- 0.4 days and 70,000 +/- 11,000 platelets/microliter per day vs. 2.8 +/- 0.6 days and 179,000 +/- 19,000 platelets/microliter per day in untreated homocystinemic controls; P less than 0.001). Sulfinpyrazone therapy also reduced the size and frequency of homocysteine-induced intimal lesion formation (P less than 0.001). Although sulfinpyrazone reduced the amount of specific 51Cr release from cultured human umbilical vein endothelial cells induced by 10 mM homocysteine after 24 hours of co-incubation, no effect was observed in assays of endothelial cell detachment when sulfinpyrazone (10(-5) M) or its thioether metabolite were pre- or co-incubated during 24 hours with homocysteine (2.5-10 mM). These data suggest that sulfinpyrazone may protect endothelial cells from injury in vivo by some apparently indirect mechanism.
Coexistence of beta 1- and beta 2-adrenoceptors in human right atrium. Direct identification by (+/-)-[125I]iodocyanopindolol binding.
Authors: Brodde O E , Karad K , Zerkowski H R , Rohm N , Reidemeister J C
Published: June 2012

The highly specific beta-adrenoceptor radioligand, (+/-)-[125I]iodocyanopindolol, has been used to subclassify beta-adrenoceptors in membranes from human right atrial appendage obtained during open heart surgery. Binding of (+/-)-[125I]iodocyanopindolol was saturable (Bmax = 86.4 +/- 7.4 fmol (+/-)-[125I]iodocyanopindolol bound/mg protein, n = 4), of high affinity (KD = 53 +/- 6 pM, n = 4), rapid, reversible, and stereospecific. The relative potencies of isoprenaline, adrenaline, and noradrenaline for inhibition of (+/-)-[125I]iodocyanopindolol binding and activation of adenylate cyclase were 1:10:10, indicating a population composed mainly of beta 1-adrenoceptors. Inhibition of (+/-)-[125I]iodocyanopindolol binding by beta 1- (practolol, metoprolol, betaxolol) and beta 2- (IPS 339, ICI 118,551, zinterol, procaterol) selective drugs, however, resulted in biphasic displacement curves with slope factors (nH, pseudo Hill coefficients) significantly less than 1.0. Nonlinear regression analysis of these curves revealed a beta 1: beta 2 ratio of 80:20 in human right atrial appendage. Nonselective beta-adrenergic drugs (propranolol, isoprenaline, and adrenaline), on the contrary, inhibited binding with monophasic displacement curves and nH = 1.0. Binding of agonists to the beta-adrenoceptors in human right atrial appendage seems to be regulated by guanyl nucleotides. In the absence of GTP, isoprenaline binds to high and low affinity state of the beta-adrenoceptors. GTP (10(-4) M) converts this heterogeneous binding into a homogeneous one of low affinity. It is concluded that, in human right atria, beta 1- and beta 2-adrenoceptors coexist; however, beta 1-adrenoceptors predominate. The physiological function of beta 2-adrenoceptors in human right atrium remains to be elucidated.
Inhibition of indium-111 platelet accretion onto venous thrombi in dogs by prostacyclin.
Authors: Czer G , Moser K M , Konopka R , Hartman M T
Published: June 2012

The known platelet anti-aggregant effects of prostacyclin (epoprostenol) suggest that it may have therapeutic potential in conditions in which the platelet plays a pathophysiological role. The growth of venous thrombi is one such condition. We have attempted to determine, in a canine model of fresh venous thrombosis, whether prostacyclin infusion inhibits platelet accretion in vivo and how this in vivo event related to hemodynamic and in vitro platelet anti-aggregant effects. Gamma camera imaging over thrombi for accretion of indium-111-labeled platelets disclosed that prostacyclin, at an infusion rate of 50 ng/kg per min, inhibited platelet accretion in vivo and resulted in a 95 +/- 4% decrease in in vitro adenosine diphosphate-induced platelet aggregation, and a decrease in mean arterial pressure to 86 +/- 4% of pre-infusion values. Step-wise decrements of prostacyclin infusion demonstrated that platelet accretion occurred in vivo at infusion rates of approximately 10-20 ng/kg per min and correlated with an in vitro adenosine diphosphate-induced aggregation of 54 +/- 13% of control values. Thus, prostacyclin, in a dose that causes only a mild decrease in systemic pressure, can completely inhibit platelet uptake onto fresh venous thrombi in the dog, and this inhibition correlates closely with in vitro adenosine diphosphate-induced platelet aggregation. The potential therapeutic implications of these findings are discussed.
Antihypertensive effect of the GABA receptor agonist muscimol in spontaneously hypertensive rats. Role of the sympathoadrenal axis.
Authors: Unger T , Becker H , Dietz R , Ganten D , Lang R E , Rettig R , Schömig A , Schwab N A
Published: June 2012

The antihypertensive action of central GABA-ergic stimulation was investigated in conscious stroke prone spontaneously hypertensive rats. Injection of the potent GABA agonist muscimol (0.01-1 microgram) into the lateral brain ventricle (icv) lowered mean arterial blood pressure (192.1 +/- 8.4 mm Hg) dose-dependently in stroke prone spontaneously hypertensive rats with a maximal fall of -52.7 +/- 5 mm Hg lasting for about 90 minutes. This was accompanied by bradycardia and sedation. Pretreatment with atropine (2 mg/kg, ip, or 15 micrograms/kg, icv) did not significantly influence the muscimol-induced fall in mean arterial pressure. In normotensive (109.3 +/- 1.9 mm Hg) Wistar-Kyoto controls, the maximal decrease in mean arterial pressure was -12.1 +/- 1.6 mm Hg from 109.3 +/- 1.9 mm Hg, and the duration of the effect was much less than in stroke prone spontaneously hypertensive rats, Following 1 microgram muscimol, icv, plasma noradrenaline did not fall significantly in stroke prone spontaneously hypertensive and Wistar-Kyoto rats, but in stroke prone spontaneously hypertensive rats, plasma adrenaline was fully suppressed (from 118.1 +/- 24.2 to 22.8 +/- 5.7 pg/ml) throughout the depressor response. The efferent sympathetic nervous activity as directly recorded from the n. splanchnicus was similar in conscious stroke prone spontaneously hypertensive and Wistar-Kyoto rats, and was moderately reduced in both strains by 1 microgram muscimol, icv.(ABSTRACT TRUNCATED AT 250 WORDS)
A comparison of calcium currents in rat and guinea pig single ventricular cells.
Authors: Josephson I R , Sanchez-Chapula J , Brown A M
Published: June 2012

The slow inward calcium currents were compared in rat and guinea pig heart using enzymatically dissociated, single ventricular cells. A single electrode voltage clamp was used, in which current and voltage were sampled separately using a time-sharing method. Spatial homogeneity of membrane potential during peak slow inward calcium current was assessed by measuring the potential with two microelectrodes 50 micron apart; the potentials were within 3 mV of each other. Peak current-voltage relations for slow inward calcium currents were similar for the two species, but the individual currents showed a faster time course of inactivation and a slower time course of recovery from inactivation for rat, compared with guinea pig. The potassium current blockers 4-aminopyridine and tetraethylammonium chloride did not produce significant effects on the net membrane currents recorded at the holding potentials (-50 to -40 mV) used in this study. The underlying mechanism for the inactivation of the slow inward calcium currents was explored using a double pulse procedure. In both rat and guinea pig heart cells prepulses to very positive potentials were associated with a partial restoration of the slow inward calcium current in the following test pulse. In addition, internal ethylene glycol-bis N,N,N',N'-tetraacetic acid or substitution of barium for calcium slowed the rate of inactivation of the slow inward calcium current in rat heart cells. Calcium activation of nonspecific currents was thought less likely to have produced these results due to the lack of effect of depolarizing prepulses on hyperpolarizing test pulses. A calcium-dependent component of inactivation may be responsible for the differences observed in both the inactivation and the recovery time courses of the slow inward calcium current in these species.
Biochemical properties of membranes isolated from calcium-depleted rabbit hearts.
Authors: Lamers J M , Stinis J T , Ruigrok T J
Published: June 2012

The purpose of this study was to define the biochemical properties of sarcolemma from the calcium-depleted rabbit heart. Calcium repletion after calcium-free perfusion results in irreversible damage to the heart (calcium paradox). No difference was found in specific activity of the Na+ -Ca++ antiporter in a crude preparation of sarcolemmal vesicles that was isolated from calcium-depleted hearts, compared with control perfused hearts. Likewise, the passive calcium efflux from sarcolemmal vesicles, preloaded with calcium via the Na+ -Ca++ antiporter, showed rates that were identical with control values. This indicates that the sarcolemma calcium permeability is not affected by calcium-free perfusion of the heart. Na+,K+ -ATPase activity in sarcolemma isolated from calcium-depleted hearts was reduced by 75% (P less than 0.005) compared with the control activity. Sarcolemmal phosphoproteins, whether produced by endogenous cyclic AMP- or calcium-calmodulin-dependent protein kinase, were not altered by calcium-free perfusion of the heart. The content of an important calcium-binding site in the myocardial cell, the sialic acid residues, was also estimated. Only a long period (60 minutes) of calcium-free perfusion resulted in a significant decrease (by 68%, P less than 0.025) of sialic acid content in the homogenate but not in the sarcolemma preparation. In hearts that were reperfused for 15 minutes with a normal calcium concentration (1.3 mM), sarcolemmal Na+,K+ -ATPase remained depressed and calcium permeability was still unchanged. It is possible that the sarcolemma isolation method selected a distinct part of the sarcolemma from the calcium-depleted and repleted heart that had no modified glycocalyx and permeability barriers to calcium ions, and that another part of the sarcolemma with altered properties was lost during the isolation procedure. Another possibility is that reconstitution processes during isolation affected membrane permeability properties. The results of the Na+,K+ -ATPase measurements provide evidence that the net calcium gain of the cells after calcium repletion may be associated, in part, with a loss in ability of the sarcolemma to remove calcium from the cytosol.