Aminoguanidine produces beneficial haemodynamic effects in a canine model of acute pulmonary thromboembolism.
OBJECTIVE
Activating the nitric oxide (NO)-cyclic guanosine 3',5'-monophosphate (cGMP) pathway improves haemodynamics following acute pulmonary thromboembolism (APT). However, the role of NO synthase (NOS) isoforms in the responses to APT has not been determined. We examined the effects of selective and non-selective inducible NOS (iNOS) inhibition.


METHODS
Haemodynamic evaluations were performed in non-embolized dogs treated with saline (control group; n = 4), L-NAME (NAME group; n = 3), or aminoguanidine (AG group; n = 3), and in dogs that received the same drugs and were embolized with 5 mL kg(-1) of clots made with autologous blood (Emb group, n = 9; NAME + Emb group, n = 4 and AG + Emb group, n = 7). The lung concentrations of nitrite/nitrate (NOx) and cGMP were determined by chemiluminescence and ELISA respectively.


RESULTS
Acute pulmonary thromboembolism increased mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) by 21.4 +/- 1.7 mmHg and by 843 +/- 34 dyn s cm(-5) m(-2), respectively, in Emb group. MPAP and PVRI increased to higher levels in the NAME + Emb group 15 min after APT and all dogs in this group died 15-30 min after APT. Conversely, lower MPAP and PVRI levels were found in the AG + Emb group 2 h after APT compared with the Emb group (both P < 0.05). Higher NOx concentrations were found in the Emb group compared with the other groups (all P < 0.05). Higher cGMP concentrations were found in the Emb and AG + Emb groups compared with the other groups (all P < 0.05).


CONCLUSIONS
These results indicate that endogenous NO protects against APT-induced cardiovascular responses. Moreover, iNOS-derived NO possibly produces unfavourable effects, which are counteracted by aminoguanidine. However, non-NO-related mechanisms may also be involved.
Dias-Junior
C A C
CA
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo - FMRP-USP, Ribeirao Preto, SP, Brazil.
Sertorio
J T C
JT
Tanus-Santos
J E
JE
D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000032:analysis / Q000378:metabolism; D004285:Dogs; D005260:Female; D006146:Guanidines / Q000627:therapeutic use*; D008168:Lung / Q000737:chemistry / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism / Q000627:therapeutic use; D009566:Nitrates / Q000032:analysis / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects