0202: Deficiency in nitric oxide decreases the microcirculation reactivity in response to acetylcholine but is not always associated with a higher blood pressure in mice

Abstract

Endothelial dysfunction is associated with cardiovascular diseases and can be evaluated in clinical setting for risk stratification in patients. Flow mediated dilation (FMD) or local acetylcholine (ACh) administration are used to assess endothelial dysfunction in arteries but also in microcirculation (MC) using Laser Doppler Flowmetry (LDF). In our study, we aim to investigate the role of nitric oxide (NO) in the endothelial response of microcirculation in vivo in mice. Two strains of mice (C57BL6 and BALBc mice; 20 weeks old) were treated with NO synthase inhibitor (L-NAME) in drinking water (1 g/L) and compared with their respective untreated controls. After 3 or 7 days of L-NAME, mice were anesthetized with isoflurane. Systolic blood pressure (SBP) was then measured by plethysmography and skin MC assessed by LDF. Blood flow was measured at baseline and in response to ACh administered by iontophoresis or during hyperemic response due to local heating at 44°C. At day 3, we observed a slight increase in SBP only in BALBc mice treated with L-NAME (+13 mmHg), not maintained at day 7. Conversely, at day 7, we observed an increase in SBP (+30 mmHg) only in L-NAME-treated C57BL6 mice. MC flow response to ACh was decreased by 65% and 58% in BALBc mice at day 3 and 7, respectively, and by 68% in C57BL6 mice only after 7 days of L-NAME treatment compared to untreated mice. No difference was observed in response to local heating, neither between strains nor after L-NAME treatment. In conclusion, skin microcirculation reactivity can be routinely assessed in vivo in mice. Our results show that a part of the transitory Ach-induced microcirculation flow increase is NO-mediated. Moreover, this decrease in NO bioavailability in microcirculation is not always associated with increase in systemic BP. Further studies are now required in order to determine if the microcirculation response to ACh could be a marker of coronary endothelial function in animal models as it is in human.