Polyamine effects on [Ca2+]i homeostasis and contractility in isolated rat ventricular cardiomyocytes

Ventura, Carlo; Ferroni, C.; Flamigni, Flavio; Stefanelli, Claudio; Capogrossi, M. C.

doi:10.1152/ajpheart.1994.267.2.h587

Cited by 16 publications

(14 citation statements)

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“…It is well known that ornithine is the precursor for the synthesis of polyamines such as spermine, spermidine, and putrescine. There have been reports that polyamine concentration alters K ϩ channel current in myocytes (41), can decrease inotropy by superfusion of exogenous polyamines (39), and can decrease calcium sensitivity (20). However, these studies show the effects of direct application of high-concentration exogenous polyamines, which is likely distinct from the smaller changes in endogenous ornithine that result from modulation of arginase activity.…”

Section: Discussionmentioning

confidence: 95%

Modulation of contractility by myocyte-derived arginase in normal and hypertrophied feline myocardium

Jung¹,

Kubo²,

Wilson³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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. Modulation of contractility by myocytederived arginase in normal and hypertrophied feline myocardium. Am J Physiol Heart Circ Physiol 290: H1756 -H1762, 2006. First published December 3, 2005 doi:10.1152/ajpheart.01104.2005.-L-Arginine, the sole substrate for the nitric oxide (NO) synthase (NOS) enzyme in producing NO, is also a substrate for arginase. We examined normal feline hearts and hearts with compensated left ventricular (LV) hypertrophy (LVH) produced by ascending aorta banding. Using Western blot analysis, we examined the abundance of arginase isozymes in crude homogenates and isolated cardiac myocytes obtained from the LVs of normal and LVH hearts. We examined the functional significance of myocyte arginase via measurement of shortening and intracellular calcium in isolated myocytes in the presence and absence of boronoethyl chloride (BEC), a specific pharmacological inhibitor of arginase. Both arginase I and II were detected in crude myocardial homogenates, but only arginase I was present in isolated cardiac myocytes. Arginase I was downregulated in LVH compared with normal. Inhibition of arginase with BEC reduced fractional shortening, maximal rate of shortening (ϩdL/dt) and relengthening (ϪdL/dt), and the peak of the free cytosolic calcium transient in normal myocytes but did not affect these parameters in LVH myocytes. These negative inotropic actions of arginase inhibition were associated with increases in cGMP generation. These studies indicate that only arginase I is present in cardiac myocytes where it tends to limit NO and cGMP production with the effect of supporting basal contractility. In experimental LVH induced by pressure overload, our studies demonstrate reduced arginase I expression and reduced functional significance, allowing greater arginine substrate availability for NO/cGMP signaling.arginase; hypertrophy; nitric oxide; guanosine 3Ј,5Ј-cyclic monophosphate; calcium AS IN THE VASCULATURE, nitric oxide (NO) synthase (NOS) regulates the generation of NO in cardiac myocytes by deaminating the amino acid substrate L-arginine to produce NO and citrulline. NO modulates cardiac contractility via activation of soluble guanylyl cyclase, inducing increases in cGMP. In turn, cGMP modulates contractility via the activation of certain phosphodiesterases, activation of protein kinase G, and by direct stimulation of calcium cycling proteins. On the other hand, there are reports that NO can alter contractility independent of cGMP by direct nitrosylation or acetylation of various channels and calcium cycling proteins.In the normal myocardium, the acute effects of increases in NO are bimodal, with a positive inotropic effect at low amounts of NO exposure but a negative one at higher amounts (28). NO donors have been shown to exhibit weak to moderate negative inotropic effects in nondiseased preparations (8,25,34). On the other hand, in pathological states, there is increasing evidence that upregulation of NOS and/or increased production of NO improves left ventricular (LV) performance and myocyt...

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Section: Discussionmentioning

confidence: 95%

Modulation of contractility by myocyte-derived arginase in normal and hypertrophied feline myocardium

Jung¹,

Kubo²,

Wilson³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…Plasma levels of spermine are extremely variable, ranging from the nanomolar to the micromolar range [37], and the most frequently reported value for spermine content in rat heart is around 400 nmol/g [38]. However, local levels of spermine may be much higher than the circulating concentration, a s reported in the nervous system, where presynaptically released spermine achieves high millimolar levels within synaptic clefts [39].…”

Section: Discussionmentioning

confidence: 99%

Cardiac Microvascular Endothelial Cells Express a Functional Ca<sup>2+</sup>-Sensing Receptor

et al. 2008

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The mechanism whereby extracellular Ca²⁺ exerts the endothelium-dependent control of vascular tone is still unclear. In this study, we assessed whether cardiac microvascular endothelial cells (CMEC) express a functional extracellular Ca²⁺-sensing receptor (CaSR) using a variety of techniques. CaSR mRNA was detected using RT-PCR, and CaSR protein was identified by immunocytochemical analysis. In order to assess the functionality of the receptor, CMEC were loaded with the Ca²⁺-sensitive fluorochrome, Fura-2/AM. A number of CaSR agonists, such as spermine, Gd³⁺, La³⁺ and neomycin, elicited a heterogeneous intracellular Ca²⁺ signal, which was abolished by disruption of inositol 1,4,5-trisphosphate (InsP₃) signaling and by depletion of intracellular stores with cyclopiazonic acid. The inhibition of the Na⁺/Ca²⁺ exchanger upon substitution of extracellular Na⁺ unmasked the Ca²⁺ signal triggered by an increase in extracellular Ca²⁺ levels. Finally, aromatic amino acids, which function as allosteric activators of CaSR, potentiated the Ca²⁺ response to the CaSR agonist La³⁺. These data provide evidence that CMEC express CaSR, which is able to respond to physiological agonists by mobilizing Ca²⁺ from intracellular InsP₃-sensitive stores.

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“…The administration of putrescine to the organ bath elicited a positive inotropism and increased intracellular cAMP levels in isolated left atrium of rats; however, a lack of effect after extracellular administration of putrescine and negative inotropism by spermidine and, specially, spermine has been reported in isolated rat ventricular cardiomyocites 27 and isolated rat heart. 28 The link between intracellular polyamines and cAMP during androgen-elicited positive inotropism was subsequently studied, and the results showed that 5a-dihydrotestosterone failed to increase intracellular cAMP in the presence of a-difluoromethylornithine, which suggests that polyamine synthesis is required for androgen increase of cAMP.…”

Section: Discussionmentioning

confidence: 93%

Role of Putrescine on Androgen-Elicited Positive Inotropism in the Left Atrium of Rats

Velasco

Secades²,

Bordallo³

et al. 2008

Journal of Cardiovascular Pharmacology

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Functional and biochemical studies were performed in isolated left atria of male Wistar rats to study whether endogenous polyamines may mediate androgen-elicited positive inotropism and their relationship with a rise in cAMP during the cardiotonic effect. 5 alpha-Dihydrotestosterone (100 microM) exposure increased intracellular putrescine as determined by HPLC, but it did not increase spermidine and spermine. This effect was antagonized by an inhibitor of ornithine decarboxylase, alpha-difluoromethylornithine (10 mM), suggesting enzyme activation. alpha-Difluoromethylornithine also antagonized androgens-elicited inotropism and the increase in intracellular cAMP. Putrescine (1 to 10 mM) elicited a concentration-dependent positive inotropism associated with the cAMP increase. The prior incubation with putrescine antagonized 5 alpha-dihydrotestosterone-elicited inotropism and did not produce sinergism on intracellular cAMP. Short-term incubation with 5 alpha-dihydrotestosterone or forskolin shifted to the left the cardiotonic effect of isoproterenol, an agonist of beta-adrenoceptors, without any increase in Emax, suggesting that a common mechanism was involved. Therefore, polyamines might modulate the cAMP production associated with the cardiotonic effect of androgens.

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Polyamine effects on [Ca2+]i homeostasis and contractility in isolated rat ventricular cardiomyocytes

Cited by 16 publications

References 0 publications

Modulation of contractility by myocyte-derived arginase in normal and hypertrophied feline myocardium

Modulation of contractility by myocyte-derived arginase in normal and hypertrophied feline myocardium

Cardiac Microvascular Endothelial Cells Express a Functional Ca<sup>2+</sup>-Sensing Receptor

Role of Putrescine on Androgen-Elicited Positive Inotropism in the Left Atrium of Rats

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