Acute modulation of myocardial function by angiotensin 1-7.
Angiotensin 1-7 is a bioactive heptapeptide of the renin-angiotensin system. Its cardiovascular actions have recently acquired growing relevance, mainly due to its counter-regulatory actions in the angiotensin cascade. The aim of the present study was to evaluate the actions of angiotensin 1-7 on myocardial function. Increasing concentrations of angiotensin 1-7 (10(-9) to 10(-5)M) were added to rabbit right papillary muscles: (1) in baseline conditions with intact endocardial endothelium (EE); (2) after selective removal of the EE with Triton X-100 (1s, 0.01%); (3) with intact EE in the presence of the Mas receptor antagonist A-779, the AT(1) receptor antagonist ZD-7155, the AT(2) receptor antagonist PD-123,319 or the nitric oxide synthesis inhibitor NG-nitro-l-arginine (l-NA). Concerning the effects on contractility, we observed a significant decrease on active tension, dT/dt(max), peak shortening and dL/dt(max) of -10.5+/-3.6%, -8.0+/-3.0%, -5.3+/-2.6% and -5.7+/-2.3%, respectively. There was no change on relaxation parameters, namely dT/dt(min) or dL/dt(min). Time to half relaxation was significantly decreased. The presence of ZD-7155 or PD-123,319 did not change these effects. However, angiotensin 1-7 effects on myocardial properties were abolished after selective EE removal and in the presence of A-779 or l-NA. In conclusion, in this animal species, angiotensin 1-7 through its binding to Mas receptor induces a negative inotropic effect modulated by the EE and nitric oxide and independent of AT(1) or AT(2) receptors activation. As the effects described in the present work were influenced by the endocardial endothelium, they may be disrupted in situations associated to endothelial dysfunction, as in heart failure or myocardial ischemia.
Castro-Chaves
Paulo
P
Department of Physiology, Faculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, Porto, Portugal.
Pintalhao
Mariana
M
Fontes-Carvalho
Ricardo
R
Cerqueira
Rui
R
Leite-Moreira
Adelino F
AF
D000803:Angiotensin I / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009287:Naphthyridines / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors
C092006:7-Ala-angiotensin (1-7); D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D009287:Naphthyridines; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011725:Pyridines; D043562:Receptors, G-Protein-Coupled; C095905:ZD 7155; D000804:Angiotensin II; C073402:PD 123319; D019335:Nitroarginine; D000803:Angiotensin I; C118790:angiotensin I (1-7)