Angiotensin II (Ang II) is metabolized from N-terminal by aminopeptidases and from C-terminal by Ang converting enzyme (ACE) to generate several truncated angiotensin peptides (Angs). The truncated Angs have different biological effects but it remains unknown whether Ang-(4-8) is an active peptide. The present study was to investigate the effects of Ang-(4-8) on hemodynamics and atrial natriuretic peptide (ANP) secretion using isolated beating rat atria. Atrial stretch caused increases in atrial contractility by 60% and in ANP secretion by 70%. Ang-(4-8) (0.01, 0.1, and 1 µM) suppressed high stretch-induced ANP secretion in a dose-dependent manner. Ang-(4-8) (0.1 µM)-induced suppression of ANP secretion was attenuated by the pretreatment with an antagonist of Ang type 1 receptor (AT₁R) but not by an antagonist of AT₂R or AT₄R. Ang-(4-8)-induced suppression of ANP secretion was attenuated by the pretreatment with inhibitor of phospholipase (PLC), inositol triphosphate (IP₃) receptor, or nonspecific protein kinase C (PKC). The potency of Ang-(4-8) to inhibit ANP secretion was similar to Ang II. However, Ang-(4-8) 10 µM caused an increased mean arterial pressure which was similar to that by 1 nM Ang II. Therefore, we suggest that Ang-(4-8) suppresses high stretch-induced ANP secretion through the AT₁R and PLC/IP₃/PKC pathway. Ang-(4-8) is a biologically active peptide which functions as an inhibition mechanism of ANP secretion and an increment of blood pressure.
Aminopeptidases ; Angiotensin II* ; Angiotensins* ; Animals ; Arterial Pressure ; Atrial Natriuretic Factor* ; Blood Pressure* ; Heart ; Hemodynamics ; Inositol ; Peptides ; Phospholipases ; Protein Kinase C ; Rats* ; Receptor, Angiotensin, Type 1 ; Signal Transduction

Objective: To investigate the cause of a botulism outbreak in several provinces in Viet Nam in 2020. Methods: An initial investigation was conducted to confirm the outbreak and to form hypotheses about the potential causes, followed by a case–control assessment of the plausible causative food item. Collected food samples were tested to identify the pathogen, and mouse bioassays were performed. Control measures were introduced to stop the outbreak and to prevent similar events in the future. Results: Twelve people in six southern provinces of Viet Nam were identified as having symptoms of botulism, of whom 11 were in critical condition requiring breathing support. A history of foods eaten in the 4 days before illness onset indicated that all the cases had eaten a tinned vegetarian pate, and a case–control assessment showed that this was significantly associated with the outbreak, with an odds ratio of 35.2 (95% confidence interval: 3.4–infinity). Clostridium botulinum type B was detected in three of eight pâté samples collected from the houses of cases. In the mouse bioassay for the toxicity of the pâté samples, all the mice died with clinical symptoms of botulism. Discussion: A tinned vegetarian pate was the plausible cause of a botulism outbreak in Viet Nam in 2020. Revision of food safety regulations to improve quality control of tinned foods to prevent future outbreaks is recommended.