Simvastatin treatment increases nitrite levels in obese women: modulation by T(-786)C polymorphism of eNOS.

OBJECTIVE AND SUBJECTS: Evidence indicates an impairment of nitric oxide (NO) in obesity. Statins present pleiotropic effects independently of cholesterol-lowering, including increasing of eNOS expression and antioxidant effects. We evaluated the effects of simvastatin treatment at 45 days on circulating nitrite (NO marker) and TBARS-MDA levels in obese women without comorbidities (hypertension, diabetes and dyslipidemia). Moreover, we verified whether obese women carrying the C variant of T(-786)C polymorphism located in eNOS may have increased levels of nitrite after treatment compared to TT genotype. RESULTS: After simvastatin treatment, while the plasma nitrite levels increased 42% (P=0.0008), the TBARS-MDA levels reduced 58% (P=0.0069). We observed increased levels of nitrite in both groups of genotypes (TT vs. TC+CC); however, rise in C-allele carriers was 60% comparing with 44% in TT. CONCLUSION: Our results demonstrated a restoration of nitrite levels in obese women treated with simvastatin, which is modulated by T(-786)C polymorphism.

Aminoguanidine produces beneficial haemodynamic effects in a canine model of acute pulmonary thromboembolism.

AIM: 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.

Relationship between systemic nitric oxide metabolites and cyclic GMP in healthy male volunteers.

AIM: Nitric oxide (NO) is an endogenous mediator of many physiological processes, many of which are mediated by cyclic guanosine 3',5'-monophosphate (cGMP). Much effort has been made to validate clinical markers of NO production or bioavailability. While the measurement of plasma nitrate, nitrite, and cGMP concentrations have been suggested to reflect endogenous production of NO, there is no study showing whether there is correlation between these three markers. In the present study, we investigate whether there is correlation between the plasma concentrations of nitrate, nitrite, and cGMP in a relatively homogeneous group of 141 healthy subjects. METHODS: Venous blood samples were collected from healthy male subjects and plasma aliquots were then immediately removed and stored at -70 degrees C until analysed in duplicate for their nitrite and nitrate content using ozone-based chemiluminescence assays. Plasma cGMP levels were determined by using a commercial enzyme immunoassay. RESULTS: While we found no significant correlation between plasma nitrite and nitrate concentrations (P = 0.747), or between plasma nitrate and cGMP concentrations (P = 0.221), a significant positive correlation was found between plasma cGMP and nitrite concentrations (P = 0.017, r(s) = 0.270). CONCLUSIONS: The significant correlation we found between plasma nitrite and cGMP concentrations is consistent with the notion that nitrite or cGMP concentrations in plasma may be useful clinical markers of NO formation in healthy subjects.