Changes in the regulation of vascular tone in adult male rats exposed to chronic hypoxia in utero

Rook, W. H., Glen, K. E., Marshall, J. M. and Coney, A. M. (2008). Changes in the regulation of vascular tone in adult male rats exposed to chronic hypoxia in utero. In: Proceedings of the Physiological Society Scientific Meeting: Physiology 2008. Physiological Society Scientific Meeting 2008, University of Cambridge, Cambridge, U.K., (). 14-16 July 2008.

Author Rook, W. H.
Glen, K. E.
Marshall, J. M.
Coney, A. M.
Title of paper Changes in the regulation of vascular tone in adult male rats exposed to chronic hypoxia in utero
Conference name Physiological Society Scientific Meeting 2008
Conference location University of Cambridge, Cambridge, U.K.
Conference dates 14-16 July 2008
Proceedings title Proceedings of the Physiological Society Scientific Meeting: Physiology 2008
Place of Publication London, England
Publisher The Physiological Society
Publication Year 2008
Sub-type Oral presentation
ISSN 1749-6187
Volume 11
Language eng
Formatted Abstract/Summary
 A suboptimal fetal environment has effects that can last into adulthood (1). Further, chronic hypoxia in utero (CHU) reduces endothelium-dependent dilatation to ACh in isolated adult male rat vessels (2). Acute systemic hypoxia induces dilatation in normal (N) rat hindlimb that is mediated by adenosine A1-receptors and nitric oxide (NO; (3)). We recently showed no role for A1-receptors in this response in CHU rats (4). We have now investigated the role of NO in the response to hypoxia in CHU rats. Pregnant Wistar dams were exposed to 12% O2 during days 0-10 (early: ECHU; n=5) or 10-20 (late: LCHU; n=6) of pregnancy - pups were born into and grown in air until 9-10 weeks old. Under anaesthesia (Alfaxan: i.v.), arterial blood pressure (ABP) and femoral vascular conductance (FVC) were recorded. Responses to 5-minute periods of hypoxia (breathing 8% O2) were measured before and after the NO synthase inhibitor L-NAME ( i.v) and during infusion of the NO-donor, sodium nitroprusside (SNP), at a rate sufficient to restore baseline FVC. At the end of the experiment, Tibialis Anterior (TA) and Soleus (SOL) muscles were removed for eNOS protein analysis by Western blotting. Results expressed as mean±SEM, analysis of FVC was on the integrated (Int) response over the 5 min periods. Statistical analysis was by repeated measures ANOVA and a group of N rats (n=6) were used to compare normal responses. Baseline ABP (N(133±3):ECHU(129±3):LCHU(127±4mmHg)) and IntFVC (10.5±0.8; 10.2±1.4; 8.1±0.6 Conductance Units (CU) respectively) were similar between groups, as were the changes in IntFVC evoked by hypoxia (9.7±1.5; 7.9±2.2; 6.2±1.4CU respectively). L-NAME induced similar hindlimb vasoconstriction in all groups (~5CU) and attenuated the hypoxia-induced increase in IntFVC though this was only significant in N rats (9.7±1.5 vs 4.0±1.0CU) - suggesting a reduced role in CHU rats for NO in the hypoxic dilatation of skeletal muscle. SNP restored baseline IntFVC and allowed for a larger NO-dependent increase in IntFVC during hypoxia in both N and LCHU (9.7±1.8 & 7.8±1.1CU respectively) but not in ECHU (5.7±1.4CU). Protein analysis showed similar levels of eNOS in all groups in TA, but in SOL muscle eNOS was increased in ECHU and LCHU compared to N rats. These results suggest that NO acts in a similar manner in both N and LCHU albeit to a lesser extent in the latter to produce an NO-dependent dilatation in hypoxia, further, it suggests this mechanism is not functional in ECHU. The fact that eNOS protein was unchanged (TA) or increased (SOL) suggests that the functional changes are not due to the lack of total eNOS protein, but more likely a reduction in NO bioavailability or eNOS function and this may have implications for the control of muscle blood flow under differing conditions.
Subjects 06 Biological Sciences
Keyword vascular tone
adult male rats
chronic hypoxia
in utero
suboptimal fetal environment
endothelium-dependent dilatation
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status Unknown
Additional Notes Session: Cardiovascular, Respiratory and Autonomic Control - Oral Communications. No. C85

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Created: Thu, 25 Feb 2010, 11:12:15 EST by Maria Campbell on behalf of Institute for Molecular Bioscience