Лікування L-аргініном змінює кінетику вивільнення оксиду азоту та супероксиду та зменшує ішемію/реперфузію у скелетних м’язах

Робота доктора Хука та його колег про те, як лікування L-аргініном змінює кінетику оксиду азоту та впливає на скелетні м’язи, опублікована в журналі Circulation, пояснює, як “зарядка нашого тіла” повинна бути інтегрована в наше повсякденне життя.

Abstract

Background: Constitutive nitric oxide synthase (cNOS) may produce species involved in ischemia/reperfusion (I/R) injury: NO in the presence of sufficient l-arginine and superoxide at the diminished local l-arginine concentration accompanying I/R.

Methods and Results: During hindlimb I/R (2.5 hours/2 hours), in vivo NO was continuously monitored (porphyrinic sensor), and l-arginine (chromatography), superoxide (chemiluminescence), and I/R injury were measured intermittently. Normal rabbits were compared with those infused with l-arginine 4 mg·kg−1·min−1 for 1 hour. In both groups, ≈6 minutes into ischemia, a rapid increase of NO from its basal level of 50±17 to 115±7 nmol/L, P<.005 (microvessels), was observed. In animals not treated with l-arginine, NO dropped below basal to undetectable levels (<1 nmol/L) during reperfusion. In animals treated with l-arginine, the decrease of NO was slower, such that substantial amounts accumulated during reperfusion (25 nmol/L). Decreased NO during I/R was accompanied by increased superoxide, which during reperfusion reached 50 nmol/L without or 23 nmol/L with l-arginine treatment. Calcium-dependent cNOS was a major source of superoxide release (inhibited 70% by L-NMMA and 25% by L-NAME) during I/R.

Conclusions: l-Arginine treatment decreased superoxide generation by cNOS while increasing NO accumulation, leading to protection from constriction (microvessel area, 17.77±0.95 versus 11.66±2.21 μm2 untreated, P<.0005) and reduction of edema after reperfusion (interfiber area, 16.56±2.13% versus 27.68±7.70% untreated, P<.005).

(Ihor Huk, Joseph Nanobashvili, Christoph Neumayer, Andreas Punz, Markus Mueller, Kaweh Afkhampour, Martina Mittlboeck, Udo Losert, Peter Polterauer, Erich Roth, Stephen Patton, and Tadeusz Malinski. Originally published 15 Jul 1997 https://doi.org/10.1161/01.CIR.96.2.667 Circulation. 1997;96:667–675)