Autoregulation and metabolic dilatation are major determinants of tone in the coronary circulation. Pressure-dependent myogenic tone may be important for autoregulation and KATP channels may be involved in metabolic dilatation. We have previously reported that KATP channels may not be required for adenosine-mediated dilatation in rat or human coronary resistance arteries (Lynch et al. 2002). The effect of decreased O2 on resistance arteries has not been directly studied. The aims of the current study were to demonstrate a hypoxic response in rat coronary resistance arteries with myogenic tone and to determine whether KATP channels are involved this response.
Wistar rats were killed by cervical dislocation and septal coronary arteries were dissected. Arteries (n = 7) were pressurised to 60 mmHg and checked for leaks. The inner diameter and wall thickness was continually monitored using a video dimension analyser. Once myogenic tone stabilized, the myogenic reactivity of vessels was determined by reducing pressure to 20 mmHg and then increasing it in 20 mmHg increments to 100 mmHg. Vessels were returned to 60 mmHg before undergoing a 10 min hypoxic challenge (I) after which normoxic (95 % air and 5 % CO2) conditions were restored. Hypoxia (< 10 mmHg O2) was induced by switching to a 95 % N2 and 5 % CO2 gas mixture. When tone returned to pre-hypoxic levels, vessels were subjected to a second hypoxic challenge (II). After 10 min glibenclamide (5 X 10-6 M) was added to the bath. Hypoxia caused a dilatation of the rat coronary artery with myogenic tone. This was unaffected by glibenclamide. Mean lumen diameters (mm) (± S.E.M.) are shown in Table 1.
It has been shown that replacement of glucose with 2-deoxyglucose can inhibit glycolysis and glycogenesis, and under these conditions rat coronary arteries can produce a hypoxic-like dilatation (Conway et al. 1994). In our preparation (n = 6) 2-deoxyglucose significantly (P < 0.05, paired t test) dilated a vessel with myogenic tone, from a diameter of 176 (11) mm to a diameter of 215 (2.7) mm. The dilatation persisted in the presence of glibenclamide (209.0 (13.6) mm).
This study implies that KATP channels are not required for hypoxic-induced relaxation of coronary resistance arteries in the rat. KATP channels do not appear to play a role in the dilator response to 2-deoxyglucose in rat coronary arteries with myogenic tone.
This work was funded by The British Heart Foundation.
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