Mechanisms of hypoxic vasodilatation of isolated rat mesenteric arteries: a comparison with metabolic inhibition
Article first published online: 8 SEP 2004
The Journal of Physiology
Volume 516, Issue 1, pages 249–259, April 1999
How to Cite
Otter, D. and Austin, C. (1999), Mechanisms of hypoxic vasodilatation of isolated rat mesenteric arteries: a comparison with metabolic inhibition. The Journal of Physiology, 516: 249–259. doi: 10.1111/j.1469-7793.1999.249aa.x
- Issue published online: 8 SEP 2004
- Article first published online: 8 SEP 2004
- (Received 26 July 1998; accepted after revision 11 December 1998)
- 1Hypoxia (PO2 < 5 mmHg) decreased vessel tone in isolated rat mesenteric arteries precontracted with either high [K+] or the thromboxane analogue U46619. This response was not altered by N-nitro-L-arginine (L-NA) and indomethacin.
- 2Simultaneous measurement of pHi and tension showed that the decrease in vessel tone was accompanied by an intracellular acidification. Similar reductions in tone and pHi were observed with the metabolic inhibitors 2,4-dinitrophenol (DNP) and sodium azide.
- 3The presence of the lactate transport inhibitor α-cyano-4-hydroxy-cinnamic acid (CHC) increased the magnitude of the acidification and resulted in a significantly faster reduction in tone in response to hypoxia. Addition of CHC to normoxic tissues caused both a vasodilatation and a reduction of pHi.
- 4A decrease in pHi induced on washout of ammonium chloride (NH4Cl) resulted in an increase in tone.
- 5Relaxation to hypoxia or metabolic inhibition was unaffected when the change in pHi was neutralized by addition of the weak base trimethylamine (TMA).
- 6It is concluded that severe hypoxia decreases tone in isolated rat mesenteric arteries by a mechanism which is independent of nitric oxide and prostaglandins. Both severe hypoxia and metabolic inhibition reduced pHi, although this does not appear to be contributing to the changes in tone observed.