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Biomedical subjects

R T Dowell

Publications and source records attributed to R T Dowell.

At least 37 records · Page 2Linked to original sources
PubMed1989

Acetylcholinesterase molecular forms in muscle and non-muscle cells of rat heart.

Experiments were performed to determine the cellular associations of the molecular forms of acetylcholinesterase (AChE) in adult rat heart. For this purpose, a cardiac muscle and a non-muscle fraction were isolated from rat heart ventricles after perfusion with collagenase and hyaluronidase, extracts of these fractions were subjected to ultracentrifugation on linear density gradients of sucrose (5-20%), and fractions of these gradients were analyzed for AChE activity. The results show that only globular AChE molecular forms were present in isolated cardiac muscle cells. Globular AChE forms were also present in the non-muscle cells fraction but in different proportions. The proportions of globular AChE forms plus the high specific activity of choline acetyltransferase in the non-muscle cell fraction suggest that this fraction contains cholinergic nerve fragments. The results of this study also show that asymmetric AChE is released during the perfusion of heart with the digestive enzymes, which suggests that asymmetric AChE is bound to the extracellular matrix of heart.

Acetylcholinesterase↗
PubMed1989

Phase resetting of respiratory rhythm: effect of changing respiratory "drive".

We studied the effect of changing drive on resetting of respiratory rhythm in anesthetized cats and in a model (Van der Pol) of a limit-cycle oscillator. In cats, rhythm was perturbed by brief mesencephalic stimuli. Stimulus time in the cycle (old phases) and times of onset of rescheduled breaths (cophases) were measured. Previous study [Paydarfar and Eldridge, Am. J. Physiol. 252 (Regulatory Integrative Comp. Physiol. 21): R55-R62, 1987] showed distinct types of phase resetting that depended on strength of stimuli. In this study, stimulus strength was kept constant, but respiratory drive was changed by increasing PCO2, by stimulating carotid sinus nerve, or by cooling intermediate areas of ventral medulla. Type 0 (strong) resetting occurred when respiratory drive was low, type 1 (weak) resetting when drive was high, and a phase singularity when drive was intermediate. Phase-resetting patterns generated by the model showed the same behavior when a drive parameter was changed. The findings support the idea that continuous limit-cycle dynamics underlie generation of respiratory rhythm. Increased respiratory drive, by increasing size of the limit cycle, reduces functional effectiveness of the same perturbing stimulus in causing phase resetting.

Animals↗
PubMed1989

Buspirone, an anxiolytic drug that stimulates respiration.

The recently released drug buspirone is an anxiolytic agent that appears not to have the sedating effects of barbiturates and benzodiazepines, both known to have respiratory depressant effects. Because of its increasing clinical use, we desired to study the effects of buspirone on respiratory control. We therefore determined central neural respiratory responses, measured from phrenic nerve activity, after intravenous administration in paralyzed, vagotomized, and glomectomized cats whose end-tidal PCO2 and body temperature were kept constant. The responses were compared to the effects of the sedating tranquilizer diazepam. Buspirone had a dose-dependent stimulatory effect on respiratory output primarily through an increase of tidal activity but with an increase of frequency in some animals. Associated with this was a shift of the apneic threshold to a lower level of PCO2 without a change of slope or shape of the CO2 response curve. In contrast, diazepam led to a depression of respiration and a shift of the apneic threshold to a higher PCO2. The findings indicate that buspirone does not have the typical neural respiratory depressant actions of diazepam but instead stimulates respiration. Although the findings will need to be shown to apply to human beings, they suggest that buspirone may be a useful drug to treat anxiety in patients without causing undesirable respiratory depression.

Animals↗
PubMed1987

Phosphorylcreatine shuttle enzymes during perinatal heart development.

Mammalian heart development, from the time of weaning until adulthood, is characterized by progressive and significant enhancement in functional performance. Aerobic metabolism and contractile protein ATPase activity increase in parallel with augmented cardiac function. The present studies examined the potential contribution of phosphorylcreatine shuttle enzymes to the developmentally linked alterations in heart performance. Mitochondrial ATPase specific activity was not altered between weanling and adult heart; however, creatine kinase activity was enhanced approximately threefold. Myofibrillar ATPase activity doubled over the developmental time course, while creatine kinase activity increased to an even greater extent. Enhanced myofibrillar ATPase activity was not due to alterations in either calcium sensitivity or ATPase activity measured in purified myosin. Both the mitochondrial and myofibrillar creatine kinase enzyme activities are enhanced during normal heart growth; however, relatively greater enhancement of the myofibrillar component occurs. Thus, enzymatic reactions comprising the phosphorylcreatine shuttle system are dramatically increased during normal heart development. This mechanism deserves consideration as a potentially powerful contributor to enhanced cardiac function during the perinatal period.

Adenosine Triphosphatases↗
PubMed1986

Mitochondrial component of the phosphorylcreatine shuttle is enhanced during rat heart perinatal development.

Aerobic metabolism is enhanced during perinatal heart development in parallel with increased cardiac function. The mitochondrial component of the phosphorylcreatine shuttle is important in providing energy for contraction and was examined in weanling and adult rat left ventricle. Creatine kinase activity was enhanced in tissue homogenate and purified cardiac myocytes of adults. Mitochondrial analyses attribute this enhancement to increased creatine kinase activity per milligram mitochondrial protein. Other enzymatic markers of mitochondrial function are not enhanced in activity during perinatal heart growth. The unique response of creatine kinase points to the shuttle mechanism and of mitochondrial creatine kinase, in particular, as a major contributor to heart functional regulation.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1985

Metabolic and cyclic nucleotide enzyme activities in muscle and nonmuscle cells of rat heart during perinatal development.

Enzyme activities related to aerobic metabolism and cyclic nucleotides were evaluated in muscle and nonmuscle cells of rat heart. The perinatal period from weaning to adult was studied. Malate dehydrogenase, citrate synthase, and 3-hydroxyacyl-CoA dehydrogenase activities of nonmuscle cells equal or exceed muscle cell activities in the weanling heart. Aerobic enzymes remain unchanged in nonmuscle cells during growth; however, muscle cell activities are enhanced. Adenylate cyclase and guanylate cyclase activities are higher in heart homogenates of weanling than adult rats. Despite elevated adenylate cyclase activity, cyclic AMP levels are identical in weanling and adult rats. Cyclic GMP levels are twofold higher in weanling than in adult rats. Muscle cell metabolism and cyclic nucleotide levels are associated with growth-related changes in heart function and cellularity, respectively.

Animals↗
PubMed1985

Cardiac myofibrillar creatine kinase is not influenced by hypothyroidism.

The cardiac myofibrillar component of the phosphorylcreatine shuttle mechanism enzymatically couples the functionally significant processes of energy utilization (ATPase) with substrate regeneration by creatine kinase (CK). Both components have isoenzyme forms that are transcriptionally regulated. Propylthiouracil-induced (PTU) hypothyroidism reduced rat cardiac contractile protein ATPase activity by shifting isomyosin predominance from the V1 to the V3 form. However, neither CK specific activity or CK isoenzyme composition was altered by PTU treatment. Thus, myofibrillar components of the phosphorylcreatine shuttle, ATPase and CK, are not coordinately regulated under hypothyroid conditions.

Adenosine Triphosphatases↗
PubMed1985

Isomyosin and thyroid hormone levels in pressure-overloaded weanling and adult rat hearts.

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.

Animals↗
PubMed1985

Postnatal development of rat heart during 6-hydroxydopamine or propranolol treatment.

Progressive postbirth development of mammalian heart contractile function is accompanied by augmentations of aerobic metabolic potential and cardiac myofibrillar ATPase activity. The temporal similarity of the above developmental sequences suggested that a single, unifying factor may coordinate myocardial maturation. It was hypothesized that cardiac sympathetic nervous system development might be regulating other aspects of myocardial growth. To test this hypothesis, previously well-defined aspects of heart metabolism and contractile protein ATPase activity were determined in rats which were either sympathectomized with 6-hydroxydopamine (6-OHDA) or subjected to chronic, beta-adrenergic blockade (propranolol) throughout the postbirth period from 3 to 6 weeks of age. Neither 6-OHDA treatment nor chronic, beta-adrenergic blockade resulted in a significant reduction of any metabolic enzyme specific activity or in myofibrillar ATPase. Myofibrillar creatine phosphokinase (CPK) activity underwent greater enhancement relative to ATPase during normal heart growth. Significant and divergent influences were exerted by 6-OHDA and propranolol drug regimens on myofibrillar CPK/ATPase enzyme activity ratio. These results indicate (a) the potential for independent regulation of myofibrillar CPK and ATPase, and (b) the advisability of evaluating CPK, ATPase, and CPK/ATPase enzymatic activities as myofibrillar correlates of heart contractile function. Nevertheless, the majority of developmentally related processes in the heart are minimally influenced by chemical sympathectomy.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1984

Metabolic and contractile function enhancement during rat heart postnatal development.

Enhanced cardiac contractile function during the early post-birth period is a mammalian characteristic; however, concurrent metabolic measurements have not been systematically carried out. To define heart postnatal development, left ventricular pressure and rate of left ventricular pressure development (dP/dt) were measured in rats at 3, 5, 7, and 9 weeks post birth. When functional measurements were completed, the heart was excised, weighed, and tissue samples were used for chemical and/or enzymatic analyses. Left ventricular weight increased approximately 5-fold over the period studied, but was outstripped by 8-fold increases in body weight. Left ventricular DNA content increased dramatically between 3 weeks and 7 weeks post birth, then stabilized between 7 and 9 weeks post birth. Minor fluctuations in phosphofructokinase and lactate dehydrogenase enzyme activities suggest that glycolytic and anaerobic metabolisms undergo relatively small alterations as normal growth and development transpire. In contrast, enzymatic indices of aerobic metabolism (citrate synthase and malate dehydrogenase) were augmented approximately 6-fold without significant change in specific enzyme activity in purified mitochondria. Thus, mitochondria accumulated more rapidly than left ventricular tissue during heart growth. Magnesium-stimulated, myofibrillar ATPase enzyme activity approximately doubled over the intervening time between 3 weeks and 9 weeks post birth. Heart contractile function is augmented during normal growth roughly in parallel with increases in cell numbers, mitochondrial mass, and myofibrillar ATPase activity.

Adenosine Triphosphatases↗
PubMed1984

Heart cyclic nucleotide responses to sustained aortic constriction in neonatal and adult rats.

The present studies examined adenosine and guanosine 3',5'-cyclic monophosphate (cAMP and cGMP) levels in left ventricular tissue of neonatal and adult rats subjected to 3-10 days of abdominal aortic constriction. Left ventricular cAMP levels were elevated after 3 days of pressure overloading in neonatal rats (2,274 +/- 430 pmol/g; mean +/- SE) compared with composite control values (1,280 +/- 124) obtained from sham-operated neonates, sham-operated adults, and aortic-constricted adult groups. cAMP levels declined progressively until, at 10 days after aortic constriction, values were lower (681 +/- 25 pmol/g) than control (1,621 +/- 107). Left ventricular cGMP level was higher in sham-operated neonatal (38 +/- 3 pmol/g) than in sham-operated adult rats (17 +/- 1) at 3 and 10 days postsurgery, but pressure overloading exerted no effect on cGMP measurements. Adenylate cyclase activity in left ventricular tissue homogenate was higher in 3-day sham-operated neonatal (58 +/- 3 pmol X mg protein-1 X min-1) compared with sham-operated adult (10 +/- 1) rats as the result of augmented nonmuscle cell activity. Elevated cAMP values in 3-day, pressure-overloaded neonates occurred despite lower adenylate cyclase activity (44 +/- 2), via degradative modulation (cAMP phosphodiesterase). Guanylate cyclase activity in left ventricular tissue was consistent with prevailing cGMP levels and was not influenced by aortic constriction. The present experiments show that neonatal cardiac enlargement is associated with biphasic alterations in cAMP level which are modulated, at least in part, via degradative reactions.

Adenylyl Cyclases↗
PubMed1984

Nutritional modification of rat heart postnatal development.

Postnatal development of the mammalian myocardium encompasses increases in cellularity, energy producing and energy utilizing systems, and concurrent augmentation of heart contractile performance. The present study disrupted normal developmental sequences by adjusting the number of newborn rats per litter at 4 days postbirth. Fast-growing (4 rats/litter), normal (8 rats/litter), or slow-growing (16 rats/litter) animals were studied when 21 days old. Left ventricular cellularity (total DNA) increased as a function of the nutritionally modified growth of the heart, having values of 562 +/- 27, 625 +/- 33, and 791 +/- 20 (SE) micrograms in 16, 8, and 4 rats/litter groups, respectively. Low levels of systolic pressure (55 + 5 mmHg) and rate of pressure development (dP/dt, 2,670 +/- 130 mmHg/s) were noted in the slow-growing rats. Growth-related augmentation of pressure and dP/dt occurred such that adult levels (104 +/- 4 mmHg; 5,810 +/- 290 mmHg/s) were observed in 21-day-old, fast-growing rats. An enzymatic marker for aerobic metabolism (malate dehydrogenase) indicated mitochondrial accumulation in excess of ventricular tissue, thereby establishing progressive increases in aerobic capacity. Myofibrillar ATPase activity was not significantly different among all groups. Thus heart contractile function during nutritionally induced changes in postnatal development is augmented in proportion to increases in heart DNA content. A positive relationship also exists between dP/dt and number of mitochondria; however, enhanced contractile function is achieved independently of myofibrillar ATPase activity level.

Animals↗
PubMed1984

Perinatal nutritional modification of weanling rat heart contractile protein.

The present study ascertained the influence of litter-size-induced perinatal nutritional modification on cardiac contractile protein enzymatic activity and isomyosin composition. Myofibrillar enzyme activities for Mg2+ -ATPase, Ca2+ -ATPase, and creatine kinase (CK) in the weanling heart were unaltered by nutritional modification. However, these enzyme activities were all significantly augmented in the adult heart. Hill plot analyses of Mg2+ -ATPase activities indicated that myofibrillar calcium regulation was not influenced by either nutritional modification or the weanling-to-adult developmental progression. Isomyosin V1 composition (90 +/- 1%) correlated with plasma thyroid hormone level in normal-growth (8/litter) weanlings. Undernutrition retarded conversion of V3 isomyosin to the V1 species while overnutrition enhanced isomyosin conversion. Isomyosin composition in weanling rats subjected to perinatal nutritional modification was independent of thyroid status. In the adult rat, plasma thyroxine levels were increased, whereas V1 isomyosin remained unchanged (88 +/- 2%) compared with that of the weanling groups. Discrepancies in the relationship between contractile protein enzymatic activities, myosin composition, and heart function are apparent between both the litter-size-adjusted weanling rats and between weanling and adult animals. These discrepancies indicate the complex relationship between heart function and contractile protein properties.

Animals↗
PubMed1983

Metabolic enzyme response in the pressure-overloaded heart of weanling and adult rats.

Weanling and adult rats were subjected to left ventricular pressure overload induced by abdominal aortic constriction. At 5 days or 5 weeks postsurgery, the left ventricle (LV) was dissected, weighed, and metabolic marker enzyme activities (mumole/g/min) of tissue homogenates were measured. Enzymes representing glycolytic (phosphofructokinase (PFK] and mitochondrial (citrate synthase (CS) and malate dehydrogenase (MDH] metabolisms were evaluated. Five days of pressure overload had detectable, but statistically nonsignificant effects on left ventricles of both weanling and adult rats. Sustained pressure overload (5 weeks) increased LV weight by 52 and 39% in weanling and adult rats, respectively. PFK activity was 24 +/- 1 (mean +/- SE) in control weanlings and was unaltered in any of the other groups. LDH isoenzyme composition was estimated by substrate inhibition (ratio 0.33/10 mM pyruvate). With normal heart development, the LDH ratio increased from 1.89 +/- 0.06 to 2.03 +/- 0.08. Pressure overload had no influence on the adult LDH ratio. Developmental LDH responses were not observed in weanling LV after 5 weeks of aortic constriction (1.74 +/- 0.06). The product of CS activity and LV weight was used to estimate mitochondrial mass in the ventricle. Mitochondria accumulated at a rate of about 5% increase per day over the intervening 5-week period of normal heart growth. Pressure overload for 5 weeks in weanling rats elicited net accumulation of mitochondria at a rate of about 9% increase per day. Mitochondrial accumulation in the adapting adult rat heart amounted to less than 1% increase per day. The results indicate that qualitative and quantitative differences exist between young and adult animals in their heart enzyme adaptive responses to pressure overloading. Divergent metabolic adaptations may contribute to heart functional differences in the enlarged heart of weanlings and adults.

Age Factors↗
PubMed1982

Hemodynamic responses to methoxamine in exercise-conditioned and aorta-constricted rats.

Hemodynamic responses to methoxamine hydrochloride (Vasoxyl) were determined in rats conditioned by a moderate treadmill exercise program and in rats subjected to 5 wk of abdominal aortic constriction. Rats of comparable age served as controls. Initial hemodynamic values for control rats were as follows: left ventricular pressure, 124 +/- 4 Torr and cardiac index, 145 +/- 8 ml . min-1 . kg-1. Although minor variations were noted, initial hemodynamic values for exercise-conditioned rats were within the normal range, and no left ventricular hypertrophy was present. Aorta-constricted rats exhibited a 50% increase in left ventricular weight and significant differences in left ventricular pressure (173 +/- 9 Torr) and cardiac index (117 +/- 10 ml . min-1 . kg-1). Sequentially increasing doses of methoxamine were infused to elevate myocardial preload and afterload. When compared with control rats, exercise-conditioned animals were better able to maintain cardiac index at comparable increases in either mean arterial or left ventricular end-diastolic pressures. In contrast, aorta-constricted rats demonstrated profound reductions in hemodynamic functions in response to methoxamine infusion. Directionally divergent hemodynamic results occur in exercise-conditioned and aorta-constricted animals when subjected to identical cardiovascular stresses.

Animals↗
PubMed1981

Constituents of lymph from the non-secreting stomach of the dog.

Gastric lymph collected from the non-secreting stomach of anesthetized dogs contained glucose, Na+, K+ and creatine phosphokinase in concentrations that were similar to those in arterial and gastric venous plasma. Gastric lymph contained greater concentrations of pyruvate and lactate than in either arterial or gastric venous blood. Gastric lymph contained a high concentration of total protein similar to that in simultaneously collected hepatic lymph. Gastric lymph was collected before and after the pylorus was ligated and the stomach distended with air. These procedures were used in another study in which total protein in gastric lymph was reported to be much lower than found in the present study. The lymph to plasma ratio for protein was decreased from 0.85 +/- .04 to 0.69 +/- .04. Pyloric ligation alone caused no change in lymph protein concentration.

Animals↗