INTRODUCTION. When arterial O2 content is reduced, reflex increases in blood flow occur in an attempt to restore local O2 supply. This "hypoxic vasodilation" involves excess levels of nitric oxide (NO). However, controversy persists as to whether this is due to increased NO production by NO synthase, increased NO generation from nitrite (by nitrite reductase), or through decreased NO metabolism by mitochondria. OBJECTIVES. To confirm that vasodilation is a NO-mediated response to tissue hypoxia, and to clarify mechanisms underlying this reflex. METHODS. Under isoflurane anaesthesia, spontaneously-breathing fluid-resuscitated male Wistar rats (250–350 g) underwent intravascular cannulation for blood pressure (ABP) monitoring, blood gas analysis, and fluid/drug administration. Tissue PO2 (tPO2) was determined using a luminescence probe placed in thigh muscle. Animals were allowed to stabilize for 300 after surgery and were then randomized to receive either room air or a hypoxic mixture (FiO2 0.125). In separate experiments both groups received, alone or in combination, a 100 continuous infusion of the non-selective NOS-inhibitor SEITU (1.5 mg/kg/min), the nitritedonor NaNO2 (0.25 mg/kg/min), or vehicle. Data shown as mean ± SD. Statistics were performed using 2-way repeated-measurement ANOVA and post-hoc Tukey’s test. RESULTS. Hypoxia significantly reduced PaO2 from a baseline level of 10.8 ± 1.1 to 6.2 ± 2.8 kPa (p\0.001); tPO2 dropped from 6.1 ± 0.8 to 3.0 ± 0.4 kPa (p\0.001). None of the interventions modified PaO2 or tPO2 levels.CONCLUSIONS. Hypoxic vasodilation is, at least in part, an NO-mediated process: hypoxia reduced ABP and tPO2, blunted the hypertensive effect of SEITU and accentuated the hypotensive effect of nitrite. We argue that, in hypoxia, NO derives only partially from NOS synthesis. Further insights into NO metabolism in hypoxia may help to better understanding mechanisms underlying haemodynamic adaptations. REFERENCES. 1. Blitzer ML, et al. Am J Physiol (Heart Circ Physiol) 1996;271:H1182–5. 2. Allen JD, et al. Br J Pharmacol 2009;158:1653–4. GRANT ACKNOWLEDGMENT. MU was supported by a Physiology Award of the Accademia Nazionale dei Lincei (Roma)/Royal Society (London).

Nitric oxide metabolism and hypoxic vasodilation / M. Umbrello, A. Dyson, B. Bollen Pinto, M. Singer. ((Intervento presentato al 24. convegno ESICM tenutosi a Berlin nel 2011.

Nitric oxide metabolism and hypoxic vasodilation

M. Umbrello
Primo
;
2011

Abstract

INTRODUCTION. When arterial O2 content is reduced, reflex increases in blood flow occur in an attempt to restore local O2 supply. This "hypoxic vasodilation" involves excess levels of nitric oxide (NO). However, controversy persists as to whether this is due to increased NO production by NO synthase, increased NO generation from nitrite (by nitrite reductase), or through decreased NO metabolism by mitochondria. OBJECTIVES. To confirm that vasodilation is a NO-mediated response to tissue hypoxia, and to clarify mechanisms underlying this reflex. METHODS. Under isoflurane anaesthesia, spontaneously-breathing fluid-resuscitated male Wistar rats (250–350 g) underwent intravascular cannulation for blood pressure (ABP) monitoring, blood gas analysis, and fluid/drug administration. Tissue PO2 (tPO2) was determined using a luminescence probe placed in thigh muscle. Animals were allowed to stabilize for 300 after surgery and were then randomized to receive either room air or a hypoxic mixture (FiO2 0.125). In separate experiments both groups received, alone or in combination, a 100 continuous infusion of the non-selective NOS-inhibitor SEITU (1.5 mg/kg/min), the nitritedonor NaNO2 (0.25 mg/kg/min), or vehicle. Data shown as mean ± SD. Statistics were performed using 2-way repeated-measurement ANOVA and post-hoc Tukey’s test. RESULTS. Hypoxia significantly reduced PaO2 from a baseline level of 10.8 ± 1.1 to 6.2 ± 2.8 kPa (p\0.001); tPO2 dropped from 6.1 ± 0.8 to 3.0 ± 0.4 kPa (p\0.001). None of the interventions modified PaO2 or tPO2 levels.CONCLUSIONS. Hypoxic vasodilation is, at least in part, an NO-mediated process: hypoxia reduced ABP and tPO2, blunted the hypertensive effect of SEITU and accentuated the hypotensive effect of nitrite. We argue that, in hypoxia, NO derives only partially from NOS synthesis. Further insights into NO metabolism in hypoxia may help to better understanding mechanisms underlying haemodynamic adaptations. REFERENCES. 1. Blitzer ML, et al. Am J Physiol (Heart Circ Physiol) 1996;271:H1182–5. 2. Allen JD, et al. Br J Pharmacol 2009;158:1653–4. GRANT ACKNOWLEDGMENT. MU was supported by a Physiology Award of the Accademia Nazionale dei Lincei (Roma)/Royal Society (London).
ott-2011
Settore MED/41 - Anestesiologia
European Society of Intensive Care Medicine
Nitric oxide metabolism and hypoxic vasodilation / M. Umbrello, A. Dyson, B. Bollen Pinto, M. Singer. ((Intervento presentato al 24. convegno ESICM tenutosi a Berlin nel 2011.
Conference Object
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/167286
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact