Positive inotropic effects of NO donors in isolated guinea-pig and human cardiomyocytes independent of NO species and cyclic nucleotides

Sarkar, David; Vallance, Patrick; Amirmansour, Charles; Harding, Siân E.

doi:10.1016/s0008-6363(00)00202-9

Cited by 28 publications

(24 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, supporting our hypothesis in which NO and ONOO À donors can have a direct effect on the modulation of the calcium channels, some recent articles reported different cGMP independent effects of NO and ONOO À donors in different cardiac preparations: a positive inotropic cGMP-independent effect on isolated rat heart, (Paolocci et al, 2000) and a soluble guanylate cyclase and cAMP independent positive inotropic effect in guinea pig and human cardiac myocytes (Sarkar et al, 2000).…”

Section: Discussionsupporting

confidence: 84%

Cyclic AMP and cyclic GMP independent stimulation of ventricular calcium current by peroxynitrite donors in guinea pig myocytes

Malan

Levi

Alloatti

et al. 2003

Journal Cellular Physiology

View full text Add to dashboard Cite

We investigated the potential involvement of peroxynitrite (ONOO(-)) in the modulation of calcium current (I(Ca)) in guinea pig ventricular myocytes with the whole-cell patch clamp technique and with cyclic AMP (cAMP) measurements. Because of the short half-life of ONOO(-) at physiological pH, we induced an increase in its intracellular levels by using donors of the precursors, nitric oxide (NO) and superoxide anion (O(2) (-)). High concentrations of NO donors, SpermineNONOate (sp/NO, 300 microM) or SNAP (300 microM) increased basal I(Ca) (50.3 +/- 4.6%, n = 7 and 46.2 +/- 5.0%, n = 13). The superoxide anion donor Pyrogallol (100 microM) also stimulated basal I(Ca) (44.6 +/- 2.8%, n = 11). At lower concentration sp/NO (10 nM) and Pyrogallol (1 microM), although separately ineffective on I(Ca), enhanced the current if applied together (33.5 +/- 0.7%, n = 7). The simultaneous donor of O(2) (-) and NO, SIN-1 (500 microM), also stimulated basal I(Ca) (22.8 +/- 2.1%, n = 13). In the presence of saturating cyclic GMP (cGMP, 50 microM) in the patch pipette or of extracellular dibutyryl cGMP (dbcGMP, 100 microM), I(Ca) was still increased by SIN-1 (32.0 +/- 6.1%, n = 4 and 30.0 +/- 5.4%, n = 8). Both Manganese(III)tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP, 100 microM) a ONOO(-) scavenger, and superoxide dismutase (SOD) (150 U/ml) reversed the stimulatory effect of SIN-1 on I(Ca) (respectively -0.6 +/- 4.1%, n = 4 and 3.6 +/- 4.3%, n = 4). Intracellular cAMP level was unaltered by SIN-1, while it was enhanced by blocking the NO-cGMP pathway with the NO synthase inhibitor L-NMMA. These results suggest that peroxynitrite donors increase cardiac calcium current without the involvement of cAMP and cGMP.

show abstract

Section: Discussionsupporting

confidence: 84%

Cyclic AMP and cyclic GMP independent stimulation of ventricular calcium current by peroxynitrite donors in guinea pig myocytes

Malan

Levi

Alloatti

et al. 2003

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…The effect of SNP was abolished by guanylyl cyclase inhibition and was mimicked by the membrane permeable analogue of cGMP 8Br-cGMP, suggesting that SNP was acting via release of NO and stimulation of guanylyl cyclase (rather than nitrosylation or generation of superoxide radicals caused by some NO donors (Sarkar et al, 2000). Surprisingly, Musialek et al (1997) concluded that, independent of the autonomic nervous system, application of exogenous NO causes a marked tachycardia due to guanylyl cyclase-cGMP dependent stimulation of I f in guinea pig SAN cells.…”

Section: Resultsmentioning

confidence: 99%

Cardiac Depression Produced by L-Arginine and Phosphodiestrase Inhibitor on Isolated Mammalian Rabbit Heart: Function of Cyclic Guanosine Monophosphate (cGMP)

Sakr¹,

Al‐Hashem²,

Alkhateeb³

et al. 2010

American J. of Pharmacology and Toxicology

View full text Add to dashboard Cite

Problem statement: Cyclic guanosine 3',5'-monophosphate cGMP is one the important second messengers that determines the cardiomyocyte activity and its role in healthy and diseased cardiac muscle is still controversial. We are reporting the effect of adding L-arginine, the NO donor that stimulates cGMP production and Sildenafil citrate (phosphodiestrase inhibitor) that inhibits cGMP hydrolyis on isolated rabbit's heart to answer: Is it safe to prescribe phosphodiestrase inhibitors for men with low cardiac output? Approach: Isolated hearts from 6 rabbits were perfused using Langendorff's apparatus in which the perfusion fluid was ringer-Locke solution, applied at constant flow rate and was continuously bubbled with a mixture of 95% oxygen and 5% carbon dioxide. Each heart served as its own control before infusion of L-arginine in concentration of 3 m mol L −1 and Sildenafil citrate 1.5 mg L −1 simultaneously. Their effects were recorded after 1, 3, 5 and 10 min. The effluent fluid was collected for cardiac enzymes assay after 5 and 10 min. Results: Data showed that the infusion of L-arginine and Sildenafil citrate produced negative inotrpic and chronotropic effects. Also, the cardiac enzymes were significantly elevated. Conclusion: The present study, which was carried out on the isolated rabbit's heart, demonstrated that increased cGMP could produce a cardioprotective role by decreasing the cardiac work, although it might be hazardous to men with depressed cardiac function.

show abstract

“…Previous studies investigating the effect of BAY 41-8543 on cardiac contractility reported heterogeneous results. Increased cGMP levels after stimulation of the sGC, as it is achieved with NO or BAY 41-8543, have been reported to have minor negative (18) or positive inotropic effects (19). In addition, stimulators of the sGC such as NO or Bay 41-8543 may produce positive inotropic effects by affecting cAMP levels through crosstalk mediated by phosphodiesterase 2 (20), 3 (21) or 5 (22,23).…”

Section: Discussionmentioning

confidence: 99%

Inhalative and intravenous stimulation of soluble guanylate cyclase reduces pulmonary vascular resistance and increases cardiac output in experimental septic shock

Kronas

Peters

Richter

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. The effects of inhaled and intravenous application of a guanylate cyclase stimulator (BAY 41-8543) on pulmonary vascular resistance (PVR) and cardiac output (CO) were investigated in an experimental model of septic shock. Following induction of septic shock, anaesthetized pigs (n=31) were randomly place into two groups receiving different interventions. Animals in the first group received intravenous BAY 41-8543 (0.6 mg), inhalative BAY 41-8543 (6 mg) or a placebo. In the second group, the dosage of BAY 41-8543 was increased two-fold or combined with inhalation of nitric oxide (iNO). Intravenous and inhaled administration of BAY 41-8543 resulted in a significantly (P<0.05) reduced PVR and increased CO compared with the placebo. Increasing the dosage of BAY 41-8543 or combining it with iNO did not further decrease PVR. The results of the present study indicate that BAY 41-8543 effectively reduces PVR and increases CO in septic shock, through inhaled or intravenous routes of administration.

show abstract

Positive inotropic effects of NO donors in isolated guinea-pig and human cardiomyocytes independent of NO species and cyclic nucleotides

Abstract: Isolated GP and human myocytes show a positive inotropic effect with certain NO donors. This is independent of sGC and cAMP. The rate of NO release from donors appears important in mediating the effect.

Cited by 28 publications

References 40 publications

Cyclic AMP and cyclic GMP independent stimulation of ventricular calcium current by peroxynitrite donors in guinea pig myocytes

Cyclic AMP and cyclic GMP independent stimulation of ventricular calcium current by peroxynitrite donors in guinea pig myocytes

Cardiac Depression Produced by L-Arginine and Phosphodiestrase Inhibitor on Isolated Mammalian Rabbit Heart: Function of Cyclic Guanosine Monophosphate (cGMP)

Inhalative and intravenous stimulation of soluble guanylate cyclase reduces pulmonary vascular resistance and increases cardiac output in experimental septic shock

Contact Info

Product

Resources

About