Assuntos
Angiotensina II/farmacologia , Miocárdio/metabolismo , Norepinefrina/metabolismo , Receptores de Angiotensina/efeitos dos fármacos , Angiotensina I/farmacologia , Angiotensina II/metabolismo , Antagonistas de Receptores de Angiotensina , Animais , Estimulação Elétrica , Cobaias , Coração/efeitos dos fármacos , Coração/fisiologia , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/metabolismo , Técnicas In Vitro , Terminações Nervosas/efeitos dos fármacos , Terminações Nervosas/metabolismo , Junção Neuromuscular/efeitos dos fármacos , Período Refratário Eletrofisiológico/efeitos dos fármacos , Estimulação Química , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismoRESUMO
Norepinephrine stores in electrically driven guinea pig isolated atria were loaded with [3H]norepinephrine, and norepinephrine release was deduced from the radioactivity efflux. Electrical field stimulation of sympathetic nerve endings was applied during the refractory period of atrial contractions. The stimulation-induced release of norepinephrine was increased by angiotensin II (Ang II) (10(-8) to 10(-6) mol/L) in a concentration-dependent manner. The maximum observed effect was a 55% augmentation. The effects of 10(-7) and 10(-6) mol/L Ang II were abolished by 10(-6) and 10(-5) mol/L of the subtype 1 Ang II receptor antagonist losartan, respectively. Losartan by itself (10(-6) mol/L) caused a 14% reduction of norepinephrine release. The subtype 2 Ang II receptor ligand PD 123319 (1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl)- 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid ditrifluoroacetate) in a concentration of 10(-4) mol/L had no detectable influence on transmitter release and did not antagonize the effect of Ang II. Angiotensin I (10(-6) and 10(-5) mol/L) increased norepinephrine release maximally by 23%. This effect was antagonized by 10(-5) mol/L losartan and did not appear in the presence of 10(-6) mol/L of the converting enzyme inhibitor ramiprilat. These results suggest that Ang II increases norepinephrine release by an activation of subtype 1 receptors, whereas angiotensin I is converted to Ang II to become effective.