The early effects of chronic hypoxia on the cardiovascular system in the rat: role of nitric oxide.
Experiments were performed under Saffan anaesthesia on normoxic (N) rats and on chronically hypoxic rats exposed to 12% O2 for 1, 3 or 7 days (1, 3 or 7CH rats): N rats routinely breathed 21% O2 and CH rats 12% O2. 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% O2 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 O2 supply. The increases in FVC evoked by acute hypoxia (8% O2 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.
Walsh
Martin P
MP
Department of Physiology, The Medical School, Birmingham B15 2TT, UK.
Marshall
Janice M
JM
D000818:Animals; D001794:Blood Pressure; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005263:Femoral Artery / Q000503:physiopathology; D006339:Heart Rate; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D012129:Respiratory Function Tests; D013997:Time Factors; D014664:Vasodilation
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester