RESUMO
The contractile effects of angiotensinogen (Aogen) and its metabolization pathways were studied on rat renal vein (RRV), rat pulmonary artery (RPA) and human umbilical vein (HUV) rings. Experiments were made in the presence or in the absence of pepstatin A (a renin inhibitor, 10 microM), captopril (an ACE inhibitor, 10 microM), chymostatin (a chymase inhibitor, 10 microM), amastatin (an aminopeptidase-A and -M inhibitor) or losartan (a specific AT1 blocker, 10 microM). On all rings, Aogen-induced contractions were reduced by pepstatin A or captopril, amplified by amastatin and blocked by losartan. Chymostatin had a stronger inhibitory effect than captopril on HUV and simultaneous administering of chymostatin and captopril prevented Aogen contractile effects on HUV. It is suggested that all studied vessels possess a local renin-angiotensin system and possibility of angiotensin II production within the vessel walls using various and species-dependent enzymatic pathways.
Assuntos
Angiotensinogênio/metabolismo , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Artéria Pulmonar/efeitos dos fármacos , Veias Renais/efeitos dos fármacos , Veias Umbilicais/efeitos dos fármacos , Angiotensinogênio/farmacologia , Animais , Humanos , Técnicas In Vitro , Masculino , Músculo Liso Vascular/metabolismo , Ratos , Ratos WistarRESUMO
In a series of experiments dealing with the effects of angiotensin I (AI) and angiotensinogen on isolated rat aorta we observed that pepstatin A was able to induce contractile effects by itself. The endothelin pathway was excluded by the inhibitory effects of captopril, chymostatin and amastatin. In addition, few preliminary experiments showed that the contractile effects of pepstatin A were inhibited by the pretreatment with losartan, an antagonist of AT1 angiotensin receptors. Pepstatin A-induced contractile effects on isolated rat aorta were inhibited with high potency by captopril, chymostatin and amastatin and were totally blocked by captopril + amastatin and captopril + chymostatin. Finally, we concluded that the pepstatin A-induced contractile effects on isolated rat aorta rings are dependent on an angiotensinogen vascular pool, compulsory involve an angiotensin-converting enzyme-1 (ACE-1) mediated pathway and one or more non-classical pathways for the generation of angiotensin peptides. Further experiments are necessary to elucidate the mechanisms associated to pepstatin A-induced effects.
