Angiotensin II induced increase in frequency of cytosolic and nuclear calcium waves of heart cells via activation of AT1 and AT2 receptors.
The aim of this work is to verify if Angiotensin II (Ang II) affects the frequency of spontaneous cytosolic and nuclear Ca2+ waves in chick embryonic cardiomyocytes and if this effect is mediated via the activation of AT1 and/or AT2 receptors. Using the rapid scan technique of confocal microscopy, we observed that Ang II (10(-8)M) increases the frequency of cytosolic and nuclear Ca2+ waves. This effect was accompanied by a decrease in the amplitude of nuclear Ca2+ waves and an absence of effect on the amplitude of cytosolic Ca2+ waves. The effect of the octapeptide on both frequency and amplitude of the nuclear waves was prevented by the AT1 receptor antagonist L158809. However, blockade of the AT2 receptor using the antagonist PD123319 (10(-7)M) only prevented the effect of Ang II on the frequency of Ca2+ waves. Furthermore, the effect was prevented by both a PKC inhibitor (bisindolylmaleimide) and a PKC activator (phorbol 12,13-dibutyrate). In addition, the Ang II effect was not prevented by the blocker of the pacemaker current If. These results demonstrate that Ang II, via the activation of its receptors AT1 and AT2, affects the frequency of spontaneous Ca2+ waves and this effect seems to be mediated by the PKC pathway.
Bkaily
Ghassan
G
Department of Anatomy & Cell Biology, Faculty of Medicine, Université de Sherbrooke, 3001-12th Avenue North, Sherbrooke, Que., Canada J1H 5N4. Ghassan.Bkaily@USherbrooke.ca
El-Bizri
Nesrine
N
Nader
Moni
M
Hazzouri
Khaled M
KM
Riopel
Julie
J
Jacques
Danielle
D
Regoli
Domenico
D
D'Orleans-Juste
Pedro
P
Gobeil
Fernand
F
Avedanian
Levon
L
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002645:Chickens; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000187:drug effects / Q000196:embryology; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D018613:Microscopy, Confocal / Q000379:methods; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects* / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D016276:Ventricular Function
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D007211:Indoles; D008301:Maleimides; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D015240:Phorbol 12,13-Dibutyrate; C070967:L 158809; D011493:Protein Kinase C; C088060:bisindolylmaleimide; D002118:Calcium