Effects of oxygen tension on endothelium dependent responses in canine coronary microvessels

The aim was to determine the direct effects of oxygen tension on endothelium dependent vasodilator responses in canine coronary microvessels.

Coronary microvessels were isolated and studied in vitro in a no flow constant pressure state using a video dimension analysing system. Microvessels were exposed to different partial pressures of oxygen. Endothelium dependent responses to acetylcholine and A23187 calcium ionophore were obtained with and without indomethacin during hyperoxia and normoxia, and compared to responses during hypoxia. Dose-response curves were also obtained to the direct smooth muscle dilator nitroprusside during normoxia and hypoxia. The reversibility of the effects of hypoxia on the acetylcholine response was studied after return to hyperoxic conditions following hypoxia.

Coronary microvessels (58-150 micron diameter) were obtained from adult mongrel dogs of either sex.

Exposure of preconstricted microvessels to hypoxia alone [PO2 5.8(0.4)kPa] resulted in a 25.9(SEM 6.8)% relaxation that was abolished by indomethacin [0.35(2.9)% relaxation]. Acetylcholine elicited dose dependent vasodilatation, with no significant differences in sensitivity between normoxia [PO2 14.6(0.04) kPa] and hypoxia: EC50 = 0.023 v 0.027 mumol.litre-1, respectively. During hyperoxia [PO2 80.2(6.0) kPa] there was a significant increase in the EC50 value to 0.09 mumol.litre-1 (hypoxia and normoxia v hyperoxia). After inhibition of prostaglandin synthesis with indomethacin, the sensitivity to acetylcholine was significantly decreased during hypoxia (EC50 = 0.16 mumol.litre-1) when compared to normoxia and hyperoxia. Indomethacin alone did not alter the acetylcholine response during normoxia and hyperoxia. As with acetylcholine, the sensitivity of indomethacin treated microvessels to A23187 was also decreased during hypoxia when compared to hyperoxia. There was no difference in the nitroprusside response during hypoxia and hyperoxia. The decreased vasodilator response to acetylcholine after hypoxia was persistent up to 2 h after return to hyperoxic conditions.

Hypoxia decreases vasodilatation due to endothelium dependent relaxing factor, and oxygen tension has an important influence on both receptor dependent and receptor independent endothelium dependent vasodilator responses in coronary microvessels. Hypoxia also induces a prostaglandin mediated dilatation of preconstricted coronary microvessels. The effects of hypoxia on endothelium dependent responses are persistent up to 2 h.