ET has been implicated in hypoxic pulmonary vasoconstriction. It is not clear whether it is involved in the systemic vascular response to acute hypoxia.

Experiments were performed on rats anaesthetised with a continuous infusion of Saffan (7-12 mg kg^-1 h^-1 I.V.) in accordance with the HO Animals (Scientific Procedures) Act, 1986. At the end of the experiment the animal was killed with an overdose of anaesthetic. In Group 1 (n = 4), ET infused at 1 nmol kg^-1 I.V. over 5 min evoked a gradual increase in arterial pressure (ABP) and increase, followed by a decrease in femoral vascular conductance (FVC: femoral blood flow divided by ABP). One hour later when baselines had stabilised, the ET receptor antagonist PD 145065, which is non-selective between ET_A and ET_B receptors, was given at 300 ng kg^-1, a dose which reduced the increase in ABP induced in the rat by chronic intermittent hypoxia (Kanagy et al. 2001). This dose had no effect on baseline ABP or FVC, but reduced the initial decrease in FVC evoked by subsequent infusion of ET at 1 nmol kg^-1, from 1.06 ± 0.17 conductance units (CU, D in integrated FVC) (mean ± S.E.M.) to 0.19 ± 0.21*, P < 0.05, Student’s paired t test). In Group 2 (n = 8), systemic hypoxia (breathing 8 % O₂ for 5 min) evoked an increase in FVC (4.13 ± 0.64 CU): this response was reduced when retested after PD 145065 (300 ng kg^-1) to 2.96 ± 0.42* CU).

These results contrasted with those obtained in Group 3. In these rats (n = 4), the nitric oxide (NO) synthesis inhibitor (L-NAME, 10 mg kg^-1 I.V.) increased baseline ABP and decreased baseline FVC and the increase in FVC evoked by 8 % O₂ was reduced from 5.11 ± 0.99 to 1.93 ± 0.49* CU, showing that the muscle vasodilator response is NO dependent (Skinner & Marshall, 1996). However, when PD 145065 (300 ng kg^-1) was given in the presence of L-NAME, there was no effect on baseline values of ABP or FVC, but the increase in FVC evoked by 8 % O₂ was accentuated (to 2.52 ± 0.50* CU).

These results indicate that exogenous ET can exert both vasodilator and vasoconstrictor influences on hindlimb skeletal muscle. The effects of the ET receptor antagonist PD 145065 suggest that endogenously released ET predominantly exerts a vasodilator influence on skeletal muscle during acute systemic hypoxia, but that when the synthesis of NO is blocked, then a vasoconstrictor influence of ET is revealed.