TY - JOUR
T1 - The early effects of chronic hypoxia on the cardiovascular system in the rat: role of nitric oxide
AU - Walsh, Martin
AU - Marshall, Janice
PY - 2006/6/1
Y1 - 2006/6/1
N2 - Experiments were performed under Saffan anaesthesia on normoxic (N) rats and on chronically hypoxic rats exposed to 12% O-2 for 1, 3 or 7 days (1, 3 or 7CH rats): N rats routinely breathed 21% O-2 and CH rats 12% O-2. The 1, 3 and 7CH rats showed resting hyperventilation relative to N rats, but baseline heart rate (HR) was unchanged and arterial blood pressure (ABP) was lowered. Femoral vascular conductance (FVC) was increased in 1 and 3CH rats, but not 7CH rats. When 1-7CH rats were acutely switched to breathing 21% O-2 for 5 min, ABP increased and FVC decreased, consistent with removal of a hypoxic dilator stimulus that is waning in 7CH rats. We propose that this is because the increase in haematocrit and vascular remodelling in skeletal muscle help restore the O-2 supply. The increases in FVC evoked by acute hypoxia (8% O-2 for 5 min) and by infusion for 5 min of alpha-calcitonin gene-related peptide (alpha-CGRP), which are NO-dependent, were particularly accentuated in 1CH, relative to N rats. The NO synthesis inhibitor L-NAME increased ABP, decreased HR and greatly reduced FVC, and attenuated increases in FVC evoked by acute hypoxia and alpha-CGRP, such that baselines and responses were similar in N and 1-7CH rats. We propose that in the first few days of chronic hypoxia there is tonic NO-dependent vasodilatation in skeletal muscle that is associated with accentuated dilator responsiveness to acute hypoxia and dilator substances that are NO -dependent.
AB - Experiments were performed under Saffan anaesthesia on normoxic (N) rats and on chronically hypoxic rats exposed to 12% O-2 for 1, 3 or 7 days (1, 3 or 7CH rats): N rats routinely breathed 21% O-2 and CH rats 12% O-2. The 1, 3 and 7CH rats showed resting hyperventilation relative to N rats, but baseline heart rate (HR) was unchanged and arterial blood pressure (ABP) was lowered. Femoral vascular conductance (FVC) was increased in 1 and 3CH rats, but not 7CH rats. When 1-7CH rats were acutely switched to breathing 21% O-2 for 5 min, ABP increased and FVC decreased, consistent with removal of a hypoxic dilator stimulus that is waning in 7CH rats. We propose that this is because the increase in haematocrit and vascular remodelling in skeletal muscle help restore the O-2 supply. The increases in FVC evoked by acute hypoxia (8% O-2 for 5 min) and by infusion for 5 min of alpha-calcitonin gene-related peptide (alpha-CGRP), which are NO-dependent, were particularly accentuated in 1CH, relative to N rats. The NO synthesis inhibitor L-NAME increased ABP, decreased HR and greatly reduced FVC, and attenuated increases in FVC evoked by acute hypoxia and alpha-CGRP, such that baselines and responses were similar in N and 1-7CH rats. We propose that in the first few days of chronic hypoxia there is tonic NO-dependent vasodilatation in skeletal muscle that is associated with accentuated dilator responsiveness to acute hypoxia and dilator substances that are NO -dependent.
UR - http://www.scopus.com/inward/record.url?scp=33746843506&partnerID=8YFLogxK
U2 - 10.1113/jphysiol.2006.108753
DO - 10.1113/jphysiol.2006.108753
M3 - Article
SN - 1469-7793
VL - 575
SP - 263
EP - 275
JO - The Journal of Physiology
JF - The Journal of Physiology
ER -