Influence of Cellular Energy Metabolism on Contractions of Porcine Carotid Artery Smooth Muscle

Dillon, Patrick F.

doi:10.1159/000054086

Cited by 8 publications

(3 citation statements)

References 19 publications

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“…Smooth muscle contractility is impaired by both hypoxia (10) and ATP depletion in the ductus (Fig. 4), as well as in other vessels (5,6,19). In the tightly constricted closed ductus, cell death and anatomic remodeling continue to hold the ductus closed despite the impaired muscle contractility.…”

Section: Discussionmentioning

confidence: 96%

Postnatal constriction, ATP depletion, and cell death in the mature and immature ductus arteriosus

Levin¹,

McCurnin²,

Seidner³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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After birth, constriction of the full-term ductus arteriosus induces oxygen, glucose and ATP depletion, cell death, and anatomic remodeling of the ductus wall. The immature ductus frequently fails to develop the same degree of constriction or anatomic remodeling after birth. In addition, the immature ductus loses its ability to respond to vasoconstrictive agents, like oxygen or indomethacin, with increasing postnatal age. We examined the effects of premature delivery and postnatal constriction on the immature baboon ductus arteriosus. By 6 days after birth, surrogate markers of hypoxia (HIF1␣/VEGF mRNA) and cell death [dUTP nick-end labeling (TUNEL)-staining] increased, while glucose and ATP concentrations (bioluminescence imaging) decreased in the immature ductus. TUNEL-staining was significantly related to the degree of glucose and ATP depletion. Glucose and ATP depletion were directly related to the degree of ductus constriction; while TUNEL-staining was logarithmically related to the degree of ductus constriction. Extensive cell death (Ͼ15% TUNEL-positive cells) occurred only when there was no Doppler flow through the ductus lumen. In contrast, HIF1␣/VEGF expression and ATP concentrations were significantly altered even when the immature ductus remained open after birth. Decreased ATP concentrations produced decreased oxygen-induced contractile responses in the immature ductus. We hypothesize that ATP depletion in the persistently patent immature newborn ductus is insufficient to induce cell death and remodeling but sufficient to decrease its ability to constrict after birth. This may explain its decreasing contractile response to oxygen, indomethacin, and other contractile agents with increasing postnatal age.

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Section: Discussionmentioning

confidence: 96%

Postnatal constriction, ATP depletion, and cell death in the mature and immature ductus arteriosus

Levin¹,

McCurnin²,

Seidner³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Elevations of both ADP and inorganic phosphate could potentially limit the rate of cross‐bridge turnover 17–19 . Although there is some uncertainty as to whether the global intracellular concentrations of ADP and/or P i required for effects on cross‐bridge kinetics to be manifested are actually reached in intact smooth muscle, 17,19 it will presumably be the local concentrations in the immediate vicinity of the contractile filaments that is the important factor. It has also been proposed recently that dynamic reorganization of actin can influence tension cost in smooth muscle 20 .…”

Section: Discussionmentioning

confidence: 99%

Energy cost of contraction in rat urinary bladder smooth muscle during anoxia

Wendt

Rutgeerts²

2003

Clin Exp Pharma Physio

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1. The aim of the present study was to investigate the effects of hypoxia on energy metabolism and contraction of rat urinary bladder smooth muscle, thereby gaining insight into the capacity of this smooth muscle to maintain contractile function when rendered hypoxic. 2. Isometric force, oxygen consumption, lactate production, heat production and unloaded shortening velocity were measured in isolated muscle strips under both aerobic and anaerobic conditions. Muscle strips were bathed in physiological saline solution with the anaerobic condition being created by replacing the oxygen bubbling the solution with nitrogen. 3. During contraction under anaerobic conditions, the rate of lactate production was increased 2.5-fold above that observed under aerobic conditions. This, however, only provided for a rate of ATP production of approximately 30% of that measured under aerobic conditions. Despite this, force maintenance was only slightly depressed, indicating that the metabolic cost of contraction was reduced in hypoxia. In support of this, the rate of heat production during contractions in anoxia was only approximately half of that under aerobic conditions, whereas, again, force was only slightly lower. Unloaded shortening velocity was significantly lower in anoxia, suggesting a slower cross-bridge turnover rate. 4. The results indicate that the economy of force maintenance is increased in bladder smooth muscle under hypoxic conditions and that this is due, at least in part, to a reduced rate of cross-bridge cycling. This may help to preserve bladder contractile function during periods of ischaemia that may be associated with bladder filling and emptying.

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“…There is a wealth of papers that show changes in parts of the contractile system using unphysiological metabolite concentrations. It is the burden of any proposal to show that a system that works in unphysiological conditions, such as altered pH, ionic strength, ATP/ADP/phosphate levels, etc., has validity under cellular conditions (Dillon, 2000). Also, changes in the concentration of a control substance must be of sufficient magnitude and within the physiological range for the system to exist in vivo.…”

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confidence: 99%