PubMed Health⌕ Search

Biomedical subjects

D K Bowles

Publications and source records attributed to D K Bowles.

28 records · Page 2Linked to original sources
PubMed1997

Heterogeneity of L-type calcium current density in coronary smooth muscle.

Heterogeneity of vascular responses to physiological and pharmacological stimuli has been demonstrated throughout the coronary circulation. Typically, this heterogeneity is based on vessel size. Although the cellular mechanisms for this heterogeneity are unknown, one plausible factor may be heterogeneous distribution of ion channels important in regulation of vascular tone. Because of the importance of voltage-gated Ca2+ channels in regulation of vascular tone, we hypothesized that these channels would be unequally distributed throughout the coronary arterial bed. To test this hypothesis, voltage-gated Ca2+ current was measured in smooth muscle from conduit arteries (>1.0 mm), small arteries (200-250 microm), and large arterioles (75-125 microm) of miniature swine using whole cell voltage-clamp techniques. With 2 mM Ca2+ or 10 mM Ba2+ as charge carrier, voltage-gated Ca2+ current density was inversely related to arterial diameter, i.e., large arterioles > small arteries > conduit. Peak inward currents (10 mM Ba2+) were increased approximately 2.5- and approximately 1.5-fold in large arterioles and small arteries, respectively, compared with conduit arteries (-5.58 +/- 0.53, -3.54 +/- 0.34, and -2.26 +/- 0.31 pA/pF, respectively). In physiological Ca2+ (2 mM), small arteries demonstrated increased inward current at membrane potentials within the physiological range for vascular smooth muscle (as negative as -40 mV) compared with conduit arteries. In addition, cells from large arterioles showed a negative shift in the membrane potential for half-maximal activation compared with small and conduit arteries (-13.23 +/- 0.88, -6.22 +/- 1.35, and -8.62 +/- 0.81 mV, respectively; P < 0.05). Voltage characteristics and dihydropyridine sensitivity identified this Ca2+ current as predominantly L-type current in all arterial sizes. We conclude that L-type Ca2+ current density is inversely related to arterial diameter within the coronary arterial vasculature. This heterogeneity of Ca2+ current density may provide, in part, the basis for functional heterogeneity within the coronary circulation.

Animals↗
PubMed1995

Exercise training alters the Ca2+ and contractile responses of coronary arteries to endothelin.

We tested the hypothesis that alterations in myoplasmic free Ca2+ (Ca(m)) regulation in coronary smooth muscle after exercise training (Ex) underlie changes in vasomotor function. Yucatan miniature pigs were endurance trained by treadmill running for 16-20 wk. Simultaneous determination of Ca(m) (fura-2 microfluorometry) and contraction during endothelin exposure in coronary arteries were then performed. Endothelin (10(-9) to 10(-7) M) was administered either cumulatively or as a single concentration. Ex significantly attenuated the Ca(m) response to 10(-9) and 10(-8) M endothelin. Developed tension was significantly diminished at 10(-8) M endothelin in Ex pigs, producing a rightward shift in the concentration-developed tension response. Attenuated Ca(m) and contractile response to 10(-8) M endothelin were present after Ex whether endothelin was applied cumulatively or as a single concentration. The developed tension-Ca(m) relationship showed an increased Ca(m) sensitivity of contraction with Ex. Endothelin (10(-8) M)-induced Ca2+ influx, estimated by Ba2+ influx in low-Na+ solution, was increased threefold in coronary arteries from Ex pigs. The decreased Ca(m) in the presence of increased divalent cation (i.e., Ca2+) influx during 10(-8) M endothelin suggests a greatly enhanced sarcolemmal Ca2+ cycling in coronary arteries from Ex pigs.

Animals↗
PubMed1994

Heterogeneity of caffeine- and bradykinin-sensitive Ca2+ stores in vascular endothelial cells.

The filling state of Ca2+ stores in endothelial cells regulates Ca2+ entry. The functional relationship between the major Ca2+ stores [i.e. Ins(1,4,5)P3-sensitive (= bradykinin-sensitive stores, 'BsS') and caffeine-sensitive stores] is unknown. In pig right-coronary-artery endothelial cells, caffeine failed to release Ca2+ in 68% of the cells (quiet-responders), but increased bradykinin (Bk)-induced Ca2+ release 2.5-fold. In Bk-pre-stimulated cells, caffeine increased Ca2+ release upon a second stimulation with Bk 3.2-fold. In quiet-responders caffeine alone did not affect net Ca2+ storage, whereas Bk or caffeine followed by Bk decreased the intracellular Ca2+ pool to 45% and 15%, respectively. Blockade of the endoplasmic-reticulum Ca2+ pump by thapsigargin unmasked the effect of caffeine in quiet-responders, resulting in a transient increase in intracellular free Ca2+ concentration ([Ca2+]i). In 37% of the cells caffeine alone transiently increased [Ca2+]i and depleted BsS. This study suggests a heterogeneity in functional organization of endothelial Ca2+ stores. In quiet-responders, caffeine translocates Ca2+ towards the BsS, whereas in overt-responders caffeine empties the BsS.

Animals↗
PubMed1994

Exercise training improves metabolic response after ischemia in isolated working rat heart.

Hearts from treadmill-trained and sedentary rats were perfused in the working heart mode. Mechanical and metabolite status was evaluated before ischemia, after 25 min of global ischemia, and after 30 min of retrograde reperfusion. After reperfusion, hearts from trained rats were found to have better recovery of contractile function, lower diastolic stiffness, greater efficiency of work, and greater extracellular calcium responsiveness than hearts from sedentary rats. Training had no significant impact on bioenergetic status before or at the end of ischemia. However, after reperfusion, both phosphocreatine and ATP were significantly higher in hearts from trained rats than from sedentary control rats. Mitochondrial function in both subsarcolemmal and intermyofibrillar subpopulations was unaffected by ischemia-reperfusion. 45Ca2+ uptake during reperfusion was significantly higher in hearts from sedentary rats than from exercise-trained rats. No differences were found in free radical production or tolerance due to training. Therefore, hearts from exercise-trained rats demonstrated an increased metabolic tolerance to ischemic-reperfusion damage, which may contribute to the improved postischemic functional recovery.

Animals↗
PubMed1992

Fructose-1,6-bisphosphate improves efficiency of work in isolated perfused rat hearts.

The purpose of this study was to determine whether exogenous fructose-1,6-bisphosphate (F-1,6-P2) directly affects myocardial hemodynamics and certain metabolic parameters. Isolated working rat hearts were perfused for 30 min with 10 mM glucose (+insulin) as the exclusive exogenous substrate followed by 15 min with glucose plus one of the following concentrations (in mM) of F-1,6-P2: 1.25, 2.5, 5, or 10, and finally returned to the glucose only buffer. Additions of 2.5 and 5 mM F-1,6-P2 decreased (P less than 0.01) oxygen consumption (VO2) by 10.8 and 17.0% and coronary flow by 8.3 and 10.3%, respectively. No changes were observed in lactate release, cardiac output (CO), peak systolic pressure, heart rate, or pressure work (PW). Efficiency, expressed as PW divided by VO2, increased with F-1,6-P2 by 8.6% with 1.25 mM (P less than 0.05), 13.2% with 2.5 mM (P less than 0.01), and 16.9% with 5 mM (P less than 0.01). F-1,6-P2 at 10 mM produced no further improvements in VO2 or efficiency but was associated with declines (P less than 0.05) in CO and PW. Glucose plus 10 mM fructose had no effects on any of the above parameters, indicating that the F-1,6-P2-induced changes were not due to changes in osmolarity or to end products of F-1,6-P2 hydrolysis. Some chelation of buffer calcium by F-1,6-P2 occurred, but when free calcium was equalized in glucose and glucose plus 5 mM F-1,6-P2 buffers, the decline in VO2 (11.5%) was still far greater than could be explained by exogenous F-1,6-P2 metabolism in the glycolytic pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Exercise training improves cardiac function after ischemia in the isolated, working rat heart.

The aim of this study was to determine whether exercise training produces a myocardium intrinsically more tolerant to ischemic-reperfusion injury. Male Fischer 344 rats were treadmill trained for 11-16 wk at one of the following intensities: LOW (20 m/min, 0% grade, 60 min/day), moderate (MOD; 30 m/min, 5% grade, 60 min/day) or intensive (INT; 10 bouts of alternating 2-min runs at 16 and 60 m/min, 5% grade). Cardiac function was evaluated both before and after 25 min of global, zero-flow ischemia in the isolated, working heart model. Compared to hearts from sedentary (SED) rats, postischemic cardiac output (CO) and work were significantly higher in all trained groups. Percent recovery of CO (relative to preischemia) was 36.0 +/- 7.1 in SED and 61.2 +/- 6.5, 68.1 +/- 9.3, and 73.2 +/- 5.0 in LOW, MOD, and INT, respectively. Postischemic increases in stroke volume with increased preload and cardiac work at high work load were significantly higher in INT compared with SED. Coronary flow during initial retrograde reperfusion was significantly enhanced with training and correlated with subsequent recovery of CO (R2 = 0.613). Furthermore, trained hearts had higher phosphocreatine (P less than 0.05) and ATP (P less than 0.01) contents after 45 min reperfusion. It is concluded that exercise training results in an intrinsic myocardial adaptation, allowing greater recovery of cardiac pump function after global ischemia in the isolated rat heart.

Adenosine Triphosphate↗
PubMed1992

Effect of downhill running on motoneuron pool excitability.

The purpose of this study was to compare alterations in motoneuron pool excitability after eccentric-biased (ECC-B) downhill running exercise with non-biased (NO-B) level running exercise. Six male subjects (25-34 yr) participated in the study, which included ECC-B exercise (-10% grade) and NO-B exercise (0% grade) at 50% of maximal O2 uptake for 20 min. The control trial consisted of 20 min of quiet rest with all subjects participating in all conditions (repeated measures). Motoneuron pool excitability was measured by the Hoffman reflex (H-wave), which was expressed as a ratio (H/M ratio) of the maximal electrically stimulated muscle action potential (M-wave). NO-B exercise resulted in a 9.3 +/- 2.7% (SE) reduction in the H/M ratio. ECC-B exercise resulted in a 24.6 +/- 5.7% reduction in the ratio (P less than 0.05 for both). The two exercise treatment conditions were also significantly different from one another (P less than 0.05). Twenty-four-hour postexercise H/M ratios were similar to baseline (P greater than 0.05). Postexercise subjective muscle soreness assessment (DOMS) produced significant increases in DOMS of 36 and 166% immediately and 24 h after exercise, respectively, for the ECC-B trial only (P less than 0.001). The data show that ECC-B exercise results in greater postexercise H/M ratio reductions than NO-B exercise and that H/M ratio changes post-ECC-B exercise are not solely associated with DOMS.

Action Potentials↗
PubMed1991

Effects of acute, submaximal exercise on skeletal muscle vitamin E.

Vitamin E is the major lipid soluble anti-oxidant and may play an important protective role against free radicals produced during exercise. The purpose of this study was to determine the effect of a submaximal exercise bout on vitamin E levels in selected tissues. Five week- old lean, female Zucker rats were randomly divided into sedentary and run groups. At least 4 days following a maximal VO2 test, the run group (n = 7) ran on a treadmill at 70.3 +/- 1.5% VO2 max for 34-42 minutes. Duration was varied according to body weight to keep total work constant. Immediately post-exercise, animals were decapitated, exsanguinated and the quadriceps (red and white vastus lateralis), liver and heart quickly excised and stored under liquid nitrogen until analyzed. Lipids were extracted in heptane and alpha-tocopherol levels determined by reverse-phase HPLC with electrochemical detection. Quadriceps vitamin-E levels declined post-exercise p less than 0.01), and in the white quadriceps from 22 +/- 2 to 16 +/- 2 (p less than 0.05) nmol/g wet weight. No change in vitamin E content was noted for either heart (113 +/- 6 vs. 110 +/- 7, p less than 0.05) or liver (68 +/- 6 vs. 78 +/- 5, p greater than 0.05). It is concluded that a single bout of submaximal treadmill running can result in a significant depletion of vitamin E in skeletal muscle.

Animals↗
PubMed1990

Protection against hypoxic injury in isolated-perfused rat heart by ruthenium red.

Changes in intracellular calcium content and energy production during the period of hypoxia appear to be necessary for the development of cellular injury. Ruthenium red, a hexavalent dye which inhibits the active uptake of calcium by mitochondria, might improve a cell's energy status thereby minimizing hypoxic injury. Rat heart tissue was perfused retrogradely with Krebs-Henseleit medium containing 2.5 mM calcium and 10 mM glucose. The infusion of 0.1, 1.0 or 1.24, but not 0.01 microM, ruthenium red throughout 60 min of hypoxia and 30 min of reoxygenation decreased, in a dose-dependent manner, the release of lactate dehydrogenase normally seen at reoxygenation. When the infusion of 1.24 microM ruthenium red was begun after 45 min of hypoxia, lactate dehydrogenase release at reoxygenation after 60 min of hypoxia was decreased, but to a lesser extent than when this agent was present throughout hypoxia. Ruthenium red, 1.24 microM, had no significant effects on coronary flow or function in oxygenated heart tissue. When present throughout hypoxia and reoxygenation, 1.24 microM ruthenium red prevented the decrease in coronary flow normally seen and allowed recovery of heart rate, +dP/dT, -dP/dT and work (defined as the product of developed pressure and heart rate) to normal levels. Significant functional protection was not evident at reoxygenation when ruthenium red was infused after 45 min of hypoxia or in the absence of glucose. Cardiac ATP, creatine phosphate and energy charge were decreased after 60 min of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗