title: Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: an endothelium-dependent effect.
abstract: Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control.
authors.affiliation: Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors.forename: A C
authors.initials: AC
authors.lastname: Celotto
authors.affiliation: Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors.forename: L G
authors.initials: LG
authors.lastname: Ferreira
authors.affiliation: Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors.forename: V K
authors.initials: VK
authors.lastname: Capellini
authors.affiliation: Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors.forename: A A S
authors.initials: AA
authors.lastname: Albuquerque
authors.affiliation: Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors.forename: A J
authors.initials: AJ
authors.lastname: Rodrigues
authors.affiliation: Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors.forename: P R B
authors.initials: PR
authors.lastname: Evora
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage*; D000137:Acid-Base Imbalance / Q000378:metabolism; D000138:Acidosis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D000208:Acute Disease; D000818:Animals; D001639:Bicarbonates / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001795:Blood Pressure Determination; D002245:Carbon Dioxide / Q000032:analysis; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology; D006985:Hyperventilation / Q000378:metabolism; D007022:Hypotension / Q000139:chemically induced*; D049449:Luminescence; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D011817:Rabbits
chemical_list: D001639:Bicarbonates; D009566:Nitrates; D009573:Nitrites; D002245:Carbon Dioxide; D009569:Nitric Oxide; D000109:Acetylcholine