Negative inotropic effects of angiotensin II, endothelin-1 and phenylephrine in indo-1 loaded adult mouse ventricular myocytes

Life Sciences ◽  
2002 ◽  
Vol 70 (10) ◽  
pp. 1173-1184 ◽  
Author(s):  
Kiyoharu Sakurai ◽  
Ikuo Norota ◽  
Hisao Tanaka ◽  
Isao Kubota ◽  
Hitonobu Tomoike ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Adult Mouse ◽  
Ventricular Myocytes ◽  
Inotropic Effects ◽  
Endothelin 1 ◽  
Adult Mouse Ventricular Myocytes ◽  
Negative Inotropic Effects

Mechanisms of the negative inotropic effects of sphingosine-1-phosphate on adult mouse ventricular myocytes

2008 ◽  
Vol 294 (2) ◽  
pp. H736-H749 ◽  
Author(s):  
Lee K. Landeen ◽  
Dorothy A. Dederko ◽  
Colleen S. Kondo ◽  
Betty S. Hu ◽  
Nakon Aroonsakool ◽  
...  
Keyword(s):  
Adult Mouse ◽  
Calcium Release ◽  
Ventricular Myocytes ◽  
Receptor Subtype ◽  
Inotropic Effects ◽  
Subtype Specificity ◽  
Sphingosine 1 Phosphate ◽  
Intracellular Ca ◽  
Adult Mouse Ventricular Myocytes ◽  
Negative Inotropic Effects

Sphingosine-1-phosphate (S1P) induces a transient bradycardia in mammalian hearts through activation of an inwardly rectifying K+ current ( IKACh) in the atrium that shortens action potential duration (APD) in the atrium. We have investigated probable mechanisms and receptor-subtype specificity for S1P-induced negative inotropy in isolated adult mouse ventricular myocytes. Activation of S1P receptors by S1P (100 nM) reduced cell shortening by ∼25% (vs. untreated controls) in field-stimulated myocytes. S1P1 was shown to be involved by using the S1P1-selective agonist SEW2871 on myocytes isolated from S1P3-null mice. However, in these myocytes, S1P3 can modulate a somewhat similar negative inotropy, as judged by the effects of the S1P1 antagonist VPC23019 . Since S1P1 activates Gi exclusively, whereas S1P3 activates both Gi and Gq, these results strongly implicate the involvement of mainly Gi. Additional experiments using the IKACh blocker tertiapin demonstrated that IKACh can contribute to the negative inotropy following S1P activation of S1P1 (perhaps through Giβγ subunits). Mathematical modeling of the effects of S1P on APD in the mouse ventricle suggests that shortening of APD (e.g., as induced by IKACh) can reduce L-type calcium current and thus can decrease the intracellular Ca2+ concentration ([Ca2+]i) transient. Both effects can contribute to the observed negative inotropic effects of S1P. In summary, these findings suggest that the negative inotropy observed in S1P-treated adult mouse ventricular myocytes may consist of two distinctive components: 1) one pathway that acts via Gi to reduce L-type calcium channel current, blunt calcium-induced calcium release, and decrease [Ca2+]i; and 2) a second pathway that acts via Gi to activate IKACh and reduce APD. This decrease in APD is expected to decrease Ca2+ influx and reduce [Ca2+]i and myocyte contractility.

scholarly journals Effects of Pioglitazone on Ventricular Myocyte Shortening and Ca2+ Transport in the Goto-Kakizaki Type 2 Diabetic Rat

2018 ◽  
pp. 57-68 ◽  
Author(s):  
K. A. SALEM ◽  
V. SYDORENKO ◽  
M. QURESHI ◽  
M. OZ ◽  
F. C. HOWARTH
Keyword(s):  
Ventricular Myocytes ◽  
Cellular Level ◽  
Diabetic Rat ◽  
Antidiabetic Agent ◽  
Inotropic Effects ◽  
And Control ◽  
Transmembrane Currents ◽  
Negative Inotropic Effects ◽  
Type 2 Diabetic

Pioglitazone (PIO) is a thiazolidindione antidiabetic agent which improves insulin sensitivity and reduces blood glucose in experimental animals and treated patients. At the cellular level the actions of PIO in diabetic heart are poorly understood. A previous study has demonstrated shortened action potential duration and inhibition of a variety of transmembrane currents including L-type Ca2+ current in normal canine ventricular myocytes. The effects of PIO on shortening and calcium transport in ventricular myocytes from the Goto-Kakizaki (GK) type 2 diabetic rat have been investigated. 10 min exposure to PIO (0.1-10 µM) reduced the amplitude of shortening to similar extents in ventricular myocytes from GK and control rats. 1 μM PIO reduced the amplitude of the Ca2+ transients to similar extents in ventricular myocytes from GK and control rats. Caffeine-induced Ca2+ release from the sarcoplasmic reticulum and recovery of Ca2+ transients following application of caffeine and myofilament sensitivity to Ca2+ were not significantly altered in ventricular myocytes from GK and control rats. Amplitude of L-type Ca2+ current was not significantly decreased in myocytes from GK compared to control rats and by PIO treatment. The negative inotropic effects of PIO may be attributed to a reduction in the amplitude of the Ca2+ transient however, the mechanisms remain to be resolved.

Mechanism of the negative inotropic effects of α1-adrenoceptor agonists on mouse myocardium

2003 ◽  
Vol 81 (8) ◽  
pp. 783-789 ◽  
Author(s):  
Daya R Varma ◽  
Hansjorg Rindt ◽  
Sylvain Chemtob ◽  
Shree Mulay
Keyword(s):  
Adult Mouse ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Inotropic Effects ◽  
Adult Mice ◽  
Pkc Isoforms ◽  
Adrenoceptor Agonists ◽  
Inotropic Responses ◽  
Negative Inotropic Effects

This study was done to identify the mechanism of the α1-adrenoceptor (AR) mediated negative inotropic effects of phenylephrine (PE) on adult mouse myocardium. As reported by others, we also found that the nonselective α1AR agonist PE produced a negative inotropic effect on ventricular strips from adult mice that was inhibited by the α1AAR antagonist 5-methylurapidil (5MU) but not by the α1BAR antagonist chloroethylclonidine (CEC) or the α1DAR antagonist BMY 7378. The selective α1AAR agonist A61603 also produced a negative inotropic effect, which was antagonized by 5MU. Phorbol 12,13-dibutyrate (activator of all PKC isoforms) mimicked the negative inotropic responses to PE and A61603. The negative inotropic effects of PE were inhibited by bisindolylmaleimide (inhibitor of all PKC isoforms) but not by Gö 6976 (inhibitor of Ca2+-dependant PKC). Rottlerin, an inhibitor of Ca2+-independent PKCδ, antagonized the negative inotropic effects of PE and A61603. PE and A61603 increased the translocation of PKCδ, which was prevented by rottlerin. These data suggest that the α1AR-mediated negative inotropy on adult mouse myocardium is signaled by Ca2+-independent PKCδ.Key words: phorbol 12,13-dibutyrate, 5-methylurapidil, BMY 7378, chloroethylclolidine, Ca2+-dependant PKC isoforms, α1A-adrenoceptor.

scholarly journals Reduction in the Amplitude of Shortening and Ca2+ Transient by Phlorizin and Quercetin-3-O-Glucoside in Ventricular Myocytes From Streptozotocin-Induced Diabetic Rats

2016 ◽  
pp. 239-250 ◽  
Author(s):  
N. N. HAMOUDA ◽  
M. A. QURESHI ◽  
J. M. ALKAABI ◽  
M. OZ ◽  
F. C. HOWARTH
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Sarcoplasmic Reticulum ◽  
Ventricular Myocytes ◽  
Diabetic Rats ◽  
Ventricular Myocyte ◽  
Inotropic Effects ◽  
Cardiovascular Morbidity And Mortality ◽  
And Control ◽  
Negative Inotropic Effects

Diabetes mellitus is the leading cause of cardiovascular morbidity and mortality. Phlorizin (PHLOR) and quercetin-3-O-glucoside (QUER-3-G) are two natural compounds reported to have antidiabetic properties by inhibiting sodium/glucose transporters. Their effects on ventricular myocyte shortening and intracellular Ca2+ in streptozotocin (STZ)-induced diabetic rats were investigated. Video edge detection and fluorescence photometry were used to measure ventricular myocyte shortening and intracellular Ca2+, respectively. Blood glucose in STZ rats was 4-fold higher (469.64±22.23 mg/dl, n=14) than in Controls (104.06±3.36 mg/dl, n=16). The amplitude of shortening was reduced by PHLOR in STZ (84.76±2.91 %, n=20) and Control (83.72±2.65 %, n=23) myocytes, and by QUER-3-G in STZ (79.12±2.28 %, n=20) and Control (76.69±1.92 %, n=30) myocytes. The amplitude of intracellular Ca2+ was also reduced by PHLOR in STZ (82.37±3.16 %, n=16) and Control (73.94±5.22 %, n=21) myocytes, and by QUER-3-G in STZ (73.62±5.83 %, n=18) and Control (78.32±3.54 %, n=41) myocytes. Myofilament sensitivity to Ca2+ was not significantly altered by PHLOR; however, it was reduced by QUER-3-G modestly in STZ myocytes and significantly in Controls. PHLOR and QUER-3-G did not significantly alter sarcoplasmic reticulum Ca2+ in STZ or Control myocytes. Altered mechanisms of Ca2+ transport partly underlie PHLOR and QUER-3-G negative inotropic effects in ventricular myocytes from STZ and Control rats.

Sign in / Sign up

Export Citation Format

Share Document