Showing papers in "Canadian Journal of Physiology and Pharmacology in 1982"

Role of free radicals in catecholamine-induced cardiomyopathy

Abstract: Effects of an antioxidant, vitamin E, and a membrane stabilizing agent, zinc, were examined on the isoproterenol-induced changes in the rat myocardium. Isoproterenol treatment (80 mg/kg given over 2 days in two equal doses) caused arrhythmias and 25% mortality within 24 h of the last injection. The ultrastructural changes in the subendocardium and in focal areas of the subepicardium included swelling of mitochondria, loss of myofibrils, cell necrosis, fibrosis, and infiltration of the affected areas by polymorphonucleocytes. Both creatine phosphate and adenosine triphosphate levels were markedly decreased in hearts from isoproterenol-treated animals. Pretreatment of the animals with vitamin E (10 mg X kg-1 X day -1 for 2 weeks) or zinc (10 mg/kg ZnSO4, twice a day for 7 days) prevented these deleterious effects of isoproterenol. Animals maintained on vitamin E deficient diet for 8 weeks were found to be more sensitive to isoproterenol-induced changes and this increased sensitivity was reversed by a 2-week feeding of the animals on the normal diet coupled with vitamin E treatment. Based on the data obtained in this study it is proposed that catecholamine-induced changes may involve free radicals, which by promoting lipid peroxidation may increase membrane permeability and lead to the development of cardiomyopathy.

The pathophysiology of superoxide: roles in inflammation and ischemia

Abstract: The superoxide radical plays major roles in the neutrophil-mediated acute inflammatory response and in postischemic tissue injury, although the sources and actions of the radical are quite differen...

Intrarenal localization of the natriuretic effect of cardiac atrial extract.

Abstract: In anesthetized rats micropuncture and microcatheterization were used to collect tubular fluid from end proximal and distal tubules and from the outer medullary collecting duct. Urine was collected at the papilla tip. Samples were taken from the same sites before and after intravenous injection of atrial tissue extract; rats injected with ventricular extract served as controls. Sodium excretion increased 17-fold after atrial extract, a significantly greater rise than the 3-fold increase after ventricular extract. Clearances of inulin and single nephron filtration rates did not change significantly in either group. Tubular fluid collection results showed a similar reduction (16 to 20%) of proximal fluid and sodium reabsorption in both groups. In the experimental group only, NaCl reabsorption failed to rise in response to increased load in the medullary collecting duct. The resulting fall in fractional reabsorption in the medullary collecting duct accounted for 80% of the natriuresis. We conclude that atria...

Further studies on free-radical pathology in the major central nervous system disorders: effect of very high doses of methylprednisolone on the functional outcome, morphology, and chemistry of experimental spinal cord impact injury

Abstract: The hypothesis that pathologic free-radical reactions are initiated and catalyzed in the major central nervous system (CNS) disorders has been further supported by the current acute spinal cord injury work that has demonstrated the appearance of specific, cholesterol free-radical oxidation products. The significance of these products is suggested by the fact that: (i) they increase with time after injury; (ii) their production is curtailed with a steroidal antioxidant; (iii) high antioxidant doses of the steroidal antioxidant which curtail the development of free-radical product prevent tissue degeneration and permit functional restoration. The role of pathologic free-radical reactions is also inferred from the loss of ascorbic acid, a principal CNS antioxidant, and of extractable cholesterol. These losses are also prevented by the steroidal antioxidant. This model system is among others in the CNS which offer distinctive opportunities to study, in vivo, the onset and progression of membrane damaging free...

Manganese neurotoxicity: a model for free radical mediated neurodegeneration?

Abstract: In man, manganese neurointoxication is characterised in the early phase by bizarre behavior reminiscent of that observed in schizophrenia. During chronic manganese intoxication the neuropsychiatric symptoms manifested earlier disappear and are followed by a permanent neurological phase typified by extrapyramidal symptoms similar to those of Parkinson's disease. Study of manganese intoxication in animals may provide important clues towards elucidation of the biochemical defect underlying neuropsychiatric as well as extrapyramidal diseases. Investigations in our laboratory suggest that neurotoxicity of manganese is an exaggeration of function in normal neuronal homeostasis. Manganese neurointoxication in neonatal rats resulted in significant depression of lipid peroxidation in several rat brain regions examined. In the striatum, lipid peroxidative activity was abolished, an effect which may be related to alteration in neurotransmitters often observed in the striatum of manganese-treated rats. The chronic, e...

Tissue fractionation studies on the relationship between an atrial natriuretic factor and specific atrial granules.

Abstract: Mammalian atrial cardiocytes contain storage granules, the specific atrial granules, which morphologically resemble granules found in polypeptide hormone producing cells. The number of these granules may be altered by manipulation of water–electrolyte balance in experimental animals hinting at a role for atrial granules in the regulation of such balance. It has been recently shown that rat atrial muscle contains a factor referred to as atrial natriuretic factor. This factor induces a very powerful diuretic and natriuretic response when injected into nondiuretic assay rats. The present investigations were carried out to determine whether there exists any relationship between atrial natriuretic factor and specific atrial granules. Using a tissue fractionation procedure for the isolation of purified rat atrial granules, it was found that the highest relative purification of natriuretic factor was obtained in granule-rich subfractions. This finding suggests that the specific atrial granules may be a storage s...

The Schild regression in the process of receptor classification.

Abstract: The history and derivation of the Schild equation is reviewed as well as the conditions under which the intercept of a Schild regression (the pA2, an empirical quantity) can be considered to be an estimate of the equilibrium dissociation constant of the antagonist for the receptor (KB). This parameter is of value in the classification of receptors. To be considered competitive (and, therefore, to be described in molecular terms by a KB), an antagonist must produce parallel displacement of agonist concentration-response curves with no alteration in the maximal response and thereby yield unambiguous dose ratios of agonist which are independent of agonist concentration. These dose ratios (dr) then can be utilized in the Schild equation (log (dr = 1) = n . log [B] - log KB, where [B] is the molar concentration of antagonist) in the form of a regression of log (dr - 1) on log [B]. If the regression is linear and has a slope of unity, the blockade is consistent with simple competitive antagonism and the intercept can be considered an estimate of the KB. Experimentally, the slope is a parameter critical to the assessment of competitivity. While a slope significantly different from unity may indicate that an antagonist is not competitive, it also may indicate that nonequilibrium exist in the experimental procedures. The importance of uptake mechanisms for agonists, with regards to producing underestimations of antagonist potency, are reviewed along with a concise model by Furchgott which conveniently incorporates these concepts. The possible significance of Schild regression slopes less than 1 and greater than 1 are discussed along with caveats regarding Schild regressions with slopes of unity but erroneous estimates at KB. Short discussions of the use of selective agonists, experiments in vivo, and the assessments of receptor differences from estimates of KB also are given.

The effect of chronic alloxan- and streptozotocin-induced diabetes on isolated rat heart performance.

Abstract: Cardiac disease is a common secondary complication appearing in chronic diabetics. Isolated perfused working hearts obtained from both acute and chronic diabetic rats have also been shown to exhibit cardiac functional abnormalities when exposed to high work loads. We studied cardiac performance at various time points after induction of diabetes in rats to determine exactly when functional alterations appeared and whether these alterations progressed with the disease state. Female Wistar rats were made diabetic by a single i.v. injection of either alloxan (65 mg/kg) or streptozotocin (STZ 60 mg/kg). Cardiac performance was assessed at 7, 30, 100, 180, 240, and 360 days after induction of diabetes using the isolated perfused working heart technique. No changes were observed in the positive and negative dP/dt development at various atrial filling pressures in the diabetic hearts 7 days after treatment. Alloxan diabetic rat hearts exhibited depressed left ventricular pressure and positive and negative dP/dt d...

Evidence for on–off control of heat dissipation from the tail of the rat

Abstract: Anterior hypothalamic temperature, tail vasoactivity, and tail heat loss were observed in unanaesthetised rats resting at an ambient temperature that was varied between 25 and 35 °C between experiments, but was held constant within an experiment Vasodilation and vasoconstriction at the tail were qualitatively detectable by the appearance and disappearance of temperature differences between the tail surface overlying the ventral arterial supply, and the lateral venous drainage Vasodilation detected this way was an abrupt singular event (being either on or off), and preceded subsequent exponential changes in tail surface temperature and heat loss Within the ambient temperature range of 29–33 °C, the following sequence occurred in a 20-min cycle, despite the noncycling constant environmental and metabolic heat loads: tail vasodilation – 02 to 04 °C fall in hypothalamic temperature – tail vasoconstriction – 02 to 04 °C rise in hypothalamic temperature This behaviour, consistent with the limit-cyclic b

Dosage effect of streptozotocin on rat tissue enzyme activities and glycogen concentration

Abstract: The effect of different dosages of streptozotocin (STZ) on selected rat tissue enzyme activities and glycogen concentration were investigated. The rats were administered STZ intravenously at 60 (ST...

Pharmacological study of the contractile activity of leukotriene C4 and D4 on isolated human airway smooth muscle.

Abstract: Synthetic leukotriene C4 (LTC4) and leukotriene D4 (LTD4) were examined on isolated human tracheal and bronchial smooth muscle. Both LTC4 and LTD4 produced slowly developing contraction of trachealis and bronchus which were submaximal (70–85% of the carbachol maximum) and were not blocked by 1.0 μM atropine, 5.0 μM mepyrarnine, or 5.6 μM indomethacin. The EC50's for LTC4 and LTD4 were 10.3 and 1.8 nM on trachealis and 1.8 and 1.7 nM on bronchus, respectively. LTD4 was in excess of 20 000 times more potent than acetylcholine on some bronchial and tracheal tissues. Similar differences in potency were obtained in some tissues when LTC4 and LTD4 were compared with histamine. Tissues pretreated for 30 min with 2.0–4.0 μM FPL-55712 were less reactive to LTC4 and LTD4 than untreated control tissues. Established contractions to LTC4 and LTD4 persisted despite washing with fresh Krebs solution, were partially reversed by FPL-55712 (0.5–10 μM) and the Ca2+ channel blocker D-600 (5–10 μM), but were completely revers...

Reduction by cytoprotective agents of ethanol-induced damage to the rat gastric mucosa: a correlated morphological and physiological study

Abstract: Acute haemorrhagic erosions were produced in chambered gastric mucosae of rats by infusion into the chamber of 40% ethanol (v/v) for 10 min, followed by 50 mM HCl for 1 h. This procedure produced erosions which extended over nearly 70% of the glandular mucosa. When one of 2% ethanol, prostaglandin E2 (75 μg/kg in either 2% ethanol or in aqueous solution), or isoproterenol (50 μg/kg) was placed in the chamber for 10 min prior to infusion of 40% ethanol, the resultant lesions were significantly reduced in area (mean lesion area 25–31% of the glandular mucosa). When compared with the effects of 40% ethanol without pretreatment, there was no consistent correlation between pretreatment with these agents and changes in mucosal potential difference (PD) or net fluxes of Na+ and H+. All of the pretreatment groups did show a reduced loss of Cl+ from the chamber in the final 10-min period of the experiments. Exposure to the "protective" agents did not result in qualitative changes in mucosal structure at either the...

Chemical and biochemical aspects of superoxide radicals and related species of activated oxygen

Abstract: The spectrum of biological processes in which oxygen is used by living systems is quite large, and the products include some damaging species of activated oxygen, particularly the superoxide radical (O-.2) and hydrogen peroxide (H2O2). Superoxide radicals and hydrogen peroxide, in turn, can lead to the formation of other damaging species: hydroxyl radicals (.OH) and singlet oxygen (1O2). Hydroxyl radicals react with organic compounds to give secondary free radicals that, in the presence of oxygen, yield peroxy radicals, peroxides, and hydroperoxides. Formation, interconversion, and reactivity of O-.2 and related activated oxygen species, methods available for their detection, and the basis of their biological toxicity are briefly reviewed.

Involvement of free radicals in the pathophysiology of ischemic heart disease.

Abstract: Acute myocardial ischemia results in a decrease in developed tension and an increase in resting tension. A breakdown of the excitation–contraction coupling system can explain the behavior of ischem...

Atrial natriuretic factor has a direct, prostaglandin-independent action on kidneys.

Abstract: Intravenous injection of a saline extract of lyophilized rat atrial myocardium into anesthetized rats caused a massive diuresis and natriuresis of short duration. There was also a significant increase in potassium excretion and a fall in urine osmolality. There were no significant changes in solute-free water reabsorption, glomerular filtration rate, renal plasma flow, or filtration fraction as measured by conventional clearance methods. Mean arterial pressure was significantly reduced during the natriuretic response. The natriuretic and diuretic response was not blocked by inhibition of prostaglandin synthesis with aspirin and indomethacin. Infusion of a small amount of atrial extract directly into the left kidney resulted in a natriuretic and diuretic response which was predominantly localized to the left kidney. It is concluded that saline extracts of rat atrial myocardium contain a potent natriuretic substance which acts directly on kidneys by a mechanism which does not depend upon increased synthesis...

Intracellular Ca2+ transients in the cat papillary muscle.

Abstract: Intracellular Ca2+ transients in cat papillary muscles were detected with the calcium-sensitive bioluminescent protein aequorin and correlated with tension development. The effects of a variety of inotropic interventions are interpreted in terms of their probable effects on Ca2+ entry, Ca2+ release, Ca2+ sequestration, and the Ca2+ -sensitivity of the contractile apparatus. In contrast to results reported in dog Purkyně strands, the aequorin signals in cat papillary muscles appear to be dominated by release of Ca2+ from intracellular stores.

Stimulation-evoked changes in extracellular K+ and Ca2+ in pyramidal layers of the rat's hippocampus

Abstract: In urethane-anaesthetized rats, ion-selective microelectrodes recorded changes in extracellular K+ and Ca2+ concentrations (Δ[K+]o and Δ[Ca2+]o in pyramidal layers of the hippocampus (mostly in area CA1), which were evoked by fimbrial – commissural stimulation. [K+]o increased linearly with frequency of stimulation up to a critical frequency, in the range of 2–5 Hz, where bursts of population spikes appeared, and then rose rapidly to reach a ceiling of 9–12 mM, During continued stimulation, [K+]o remained well above the resting level of about 3.0 mM. At the end of stimulation [K+]o returned to the base line with a half time of 4–8 s, and a minor undershoot of was detectable for 1–2 min. When stimulating at frequencies above the critical value, a sharp fall in [Ca2+]o (by an average of one-third below the mean resting level of 1.4 mM) consistently started 1–5 s after the onset of the rapid phase of Δ[K+]o. [Ca2+]o typically reached a minimum in 5–10 s and immediately started to return towards the base line...

The 10th J. A. F. Stevenson Memorial Lecture Outline of a physical theory of physiological systems

Abstract: I examine the scientific status of "organismic biology" and find it to be weak and vitalistic. I propose that we now need integrative theories based on a physical approach to biology. Certain technical terms about systems, regulation and control, and the minimum requirements of a physical theory for an organism are defined. Homeostasis, the earlier first theory of physiological stability, is shown to be incomplete. I then introduce a physical theory for complex systems (homeokinetics) based upon statistical mechanics, nonlinear dynamics, and irreversible thermodynamics. The question of whether or not biological systems lie within the domain reachable by such physical analysis is considered in detail, and answered in the affirmative. I then give highlights of the physical theory to be invoked. Following the work of A. S. Iberall, I introduce a generalized stress tensor that shows in what way complex systems that internalize most of their transformations of energy can be examined from a statistical mechanic...

Effect of hypercalcemia on renal tubular handling of calcium and magnesium

Abstract: Tubular calcium and magnesium transport was investigated in thyroparathyroidectomized rats following acute elevation of extracellular calcium concentration. Fractional urinary excretion of calcium increased from 0.2 to 8.3% and magnesium increased from 15 to 39%, while sodium increased modestly from 0.1 to 1.1%. Superficial proximal tubules, Henle's loop, and distal tubules were perfused in vivo to determine the segmental effects of hypercalcemia. Fractional calcium absorption within the loop of Henle was significantly less in the hypercalcemic rats (58%) compared with normal animals (86%). Magnesium transport was inhibited to a greater extent compared with calcium in the loop as the fractional reabsorption decreased from 78% in the normal rats to 35% in the hypercalcemic animals. Sodium absorption was inhibited by 8%. Absolute calcium and magnesium absorption within the superficial distal convoluted tubule increased about three- to four-fold with increased delivery to this segment. These data indicate that hypercalcemia inhibits calcium and magnesium transport relatively more than sodium absorption in the loop of Henle and that this action principally accounts for the increase in urinary excretion of these electrolytes.

The effects of L-glutamate and its analogues upon the membrane conductance of central murine neurones in culture.

Abstract: Neurones from brain and spinal cord of foetal mice were grown dissociated in monolayer cultures for 4–6 weeks prior to electropharmacological analysis. Neurones were immersed in a Hanks balanced salt solution while drugs and ions were applied by pressure microperfusion during intracellular recordings obtained by conventional techniques. L-Glutamate and its analogues, L-aspartate, DL-homocysteate, N-methyl-D-aspartate, and DL-ibotenate activated two distinct mechanisms of excitation. The primary effect was depolarization accomplished by an apparent decrease of neurone input conductance (Gm). However, in most instances an expected increase in Gm was also observed, especially if membrane potential was reduced by tonic depolarization. Another glutamate analogue, DL-kainate, never decreased Gm and invariably increased Gm at all membrane potentials tested. The decrease of Gm evoked by glutamate and related compounds was strongly dependent upon membrane potential. It was most pronounced at potentials near restin...

A model for intracellular energy transport.

Abstract: A model for oxygen transfer to cells from capillaries is considered in which mitochondria are either clustered at the cell periphery around capillaries or homogeneously distributed through the cytosol. The capillary required to supply cells utilizing oxygen at the same rate is much less when mitochondria cluster around capillaries. Two alternative mechanisms are considered for distributing energy from peripheral mitochondria to the rest of the cell; i.e., diffusion of ATP or creatine phosphate with enough creatine kinase to ensure equilibrium between the ~P carriers. The latter has clear advantages and would appear to be adequate to supply a fairly large mitochondria-free cell core (e.g., 24-μm diameter) with very little change in ADP levels or in the free energy of ATP hydrolysis at maximum work rates. Thus, a viable alternative to the traditional Krogh model is presented which takes into account the inhomogeneity of the diffusion pathway as a result of mitochondrial clustering.

Response of blood pressure and cardiac myosin polymorphism to swimming training in the spontaneously hypertensive rat

Abstract: Cardiac muscle can adapt to different functional demands, as evidenced by polymorphism of myosin. Pressure load in spontaneously hypertensive rats induced a shift of the myosin isoenzymes towards myosin V3 (18% V1, 27% V2, 55% V3) relative to normotensive Wistar rats (49% V1, 29% V2, 22% V3). A swimming routine with Wistar rats resulted in a shift towards myosin V1 (72% V1, 18% V2, 10% V3). The training effect is not restricted to normotensive rats, since spontaneously hypertensive rats subjected to the same swimming routine exhibited a myosin isoenzyme pattern (38% V1, 31% V2, 31% V3) approaching that of the sedentary Wistar rats. Swimming training can, therefore, prevent the myosin isoenzyme redistribution towards myosin V3 found in sedentary spontaneously hypertensive rats. Furthermore, systolic blood pressure was significantly reduced (130 ± 8 mmHg (1 mmHg = 133.322 Pa)) in the swim-trained compared with the sedentary spontaneously hypertensive rats (157 ± 12 mmHg). The training-induced changes in myo...

Functional capillary density in normal and transplanted rat hearts

Abstract: The subepicardial capillaries were visualised under normoxemia and hypoxemia by cinemicrophotography of the beating heart in open-chest rats. The functional intercapillary distances (ICD) were directly measured from focused frames. Under normoxemia, the average ICD was 19.2 μm and under hypoxemia, 17.9 μm (p < 0.01). This decrease of 1.3 μm under hypoxemia corresponds to an average recruitment of an additional 416 capillaries/mm2 (from 2762 to 3178).During postnatal development, both the normoxemic and hypoxemic ICD's increased with left ventricular weight. The regression analysis of this relationship indicates that the hypoxemic ICD's remain significantly shorter within the observed range.In heterotopicall y isotransplanted, empty, beating rat hearts, there was no difference in functional ICD between normoxemia and hypoxemia either in 1-day-old (18.5 versus 18.6 μm) or in 7-day-old (17.1 versus 17.1 μm) transplants.Unlike the hearts in situ which could be observed only through a long working distance, lo...

Renal intracortical blood flow and renin secretion after denervation by 6-hydroxydopamine

Abstract: A new method of unilateral renal denervation (DNX) was developed in dogs by rapidly injecting 6-hydroxydopamine (6-OHDA) into the renal artery with simultaneous collection of the venous effluent to avoid systemic effects. The procedure induced a 93.1 ± 2.7% destruction of the adrenergic innervation as assessed by a histochemical fluorescence technique. A comparative study of both kidneys was carried out 3 days after DNX. Renal blood flow (RBF) and its cortical distribution were measured with radioactive microspheres at mean perfusion pressures of 117 mmHg (1 mmHg = 133.322 Pa) (normotension) and 70 mmHg (hypotension). The comparison of renal perfusion between kidney halves revealed a remarkable perfusion symmetry during normotension and hypotension in both the intact and the DNX kidney. Renal DNX by 6-OHDA did not alter RBF when the kidneys were perfused at normotension. During hypotension, RBF fell by 45% on the control side, while a nonsignificant decrease was noted in the DNX kidney. The redistribution...

Photoperiodicity and circannual levels of LH, FSH, and testosterone in normal and castrated male, white-tailed deer.

Abstract: To establish the relation between photoperiodicity and the levels of LH, FSH, and testosterone (T) in plasma, three intact and three castrated adult male white-tailed deer were sampled once a month for 2–3 years. The range of average LH levels in controls varied between 0.8 and 2.0 ng/mL; the levels in castrates were considerably higher, 3.4 to 8.9 ng/mL. Average levels of FSH varied in controls between 25 and 112 ng/mL and in castrates between 141 and 240 ng/mL. A significant correlation between the seasonal time course of LH and FSH was found in castrated, but not in intact bucks. In castrates both gonadotropins exhibit two major elevations coinciding with spring and fall equinoxes in March and September. The seasonal time course of FSH in castrates correlates highly with seasonal levels of FSH in controls. However, the time course of the LH curve in controls is substantially different from the curve in castrates, presumably owing to feedback mechanisms. A possible role of testicular estradiol in this f...

Halogenated biphenyls: molecular toxicology.

Abstract: The biologic and toxic effects of polychlorinated biphenyls (PCBs) are remarkably dependent on their structure. The most toxic PCBs, namely 3,3′,4,4′-tetra-, 3,3′,4,4′,5-penta- and 3,3′,4,4′,5,5′-h...

Ca2+ coupling in vascular smooth muscle: Mg2+ and buffer effects on contractility and membrane Ca2+ movements.

Abstract: An examination of the literature, over the past two decades, reveals that (1) in studies of different types of vascular smooth muscles, Mg2+ is often either left out of physiological salt solutions or reduced in concentration compared with that in blood; and (2) when excitation--contraction coupling processes have been examined in isolated vascular tissues and cells, a number of artificial (synthetic) amine and organic zwitterion buffers have often been substituted for the naturally occurring bicarbonate and phosphate anions found in the blood and in cells. The influence of extracellular magnesium ions ([Mg2+]0) on tone, contractility, reactivity, and divalent cation movements in vascular smooth muscles, and how they may relate to certain vascular disease states, is reviewed. Data are presented and reviewed which indicate that many of the most commonly used artificial buffers (e.g., Tris, HEPES, MOPS, Bicine, PIPES, imidazole) can exert adverse effects on contractility and reactivity of certain arterial and venous smooth muscles. The data reviewed herein suggest that [Mg2+]0 and membrane Mg are important in the regulation of vascular tone, vascular reactivity, and in control of Ca uptake, content, and distribution in smooth muscle cells. [HCO3-]0 and (or) PO4(2-) anions may be important for normal maintenance of excitability and reactivity and in the control of Ca uptake, content, and distribution in smooth muscle cells.

Unilaterality of the sympathetic innervation of each pad of rat interscapular brown adipose tissue

Abstract: The effects of sham, unilateral, and bilateral surgical denervation of rat interscapular brown adipose tissue (IBAT) on blood flow to the two IBAT pads of cold-acclimated (CA) rats during exposure of the animals to 22 or -6 degrees C and on the noradrenaline (NA) content and total dopamine beta-hydroxylase (DBH) (EC 1.14.17.1) activity of the pads in both warm-acclimated (WA)rats and CA rats were examined. Increase in IBAT blood flow upon cold exposure was taken as an index of sympathetically medicated calorigenesis in the tissue, and decreases in tissue levels of NA and DBH served as indices of the extent of destruction of the sympathetic innervation. At 24 h postsurgery, denervated pads of CA rats, rats, whether from unilaterally or bilaterally denervated IBAT, had less than 3% of the NA, 40-44% of the DBH, and 0% of the 10-fold, cold-induced increase in blood flow measured in intact pads of CA rats with sham-operated or unilaterally denervated IBAT. IBAT bilaterally denervated for 24 h was as responsive in terms of its maximum increase in blood flow during infusion of CA rats with NA as intact IBAT. DBH in denervated pads of both WA rats and CA rats fell to 5% or less of control levels at 2 days postdenervation and remained at these low levels, as did NA, for at least 8 weeks. These results strongly support the longstanding but recently challenged hypothesis that each pad of rat IBAT is independently innervated by sympathetic fibers.

The effects of chronic ethanol consumption on cardiac function in rats.

Abstract: A pharmacological model of alcoholism in rats was developed by administering ethanol in their drinking water. This model has provided us with a convenient means to study the effects of chronic ethanol consumption on cardiac functional properties. Our "treated" animals consumed, on the average, an equivalent of 11.1 g/kg of absolute ethanol per day and had an average blood ethanol concentration of 26.9 mg/dL at the end of the 12-week treatment period. The Langendorff-perfused hearts from both treatment and control groups performed equally well mechanically when left to beat spontaneously, but under conditions of electrical pacing the contractile ability of hearts from the alcohol-treated animals deteriorated more rapidly. Dose-response relationships for isoproterenol (isopropylnoradrenaline, IPNA) showed that hearts from alcohol-treated animals did not respond as well as hearts from control animals at higher doses of IPNA. This trend was completely reversed in the presence of low external calcium where the hearts from alcohol-treated animals responded better at all IPNA concentrations. Our observations suggest that chronic alcohol consumption may give rise to alterations in calcium ion handling at the level of myocardial plasma membranes.

Effects of estradiol on intact and denervated striatal dopamine receptors and on dopamine levels: a biochemical and behavioral study

Abstract: The present study describes the effect of chronic estrogen treatment on striatal dopamine levels and dopamine receptors, as well as on apomorphine-induced circling, a behavioral model reflecting do...