1. The number of β-adrenoceptors and their affinity for the radioligand 125I-labelled cyanopindolol (125I-CYP) were measured in crude membrane preparations of left ventricle, spleen and lung from Wistar rats exposed to 28 days continuous hypoxia.

2. β-Adrenoceptor density in the left ventricle was not significantly altered after exposure to chronic hypoxia (binding site maxima, Bmax: normoxic control 36 sem 5, hypoxic 24.8 sem 2 fmol/mg of protein). There was no change in β-adrenoceptor number in the spleen in response to chronic hypoxia (Bmax: normoxic control 76 sem 19 fmol/mg of protein, hypoxic 80 sem 15 fmol/mg of protein).

3. Chronic hypoxia resulted in a significant increase in β-adrenoceptor number in lung tissue (binding site maxima, Bmax.: normoxic control 406 (sem 31) fmol/mg of protein; hypoxic 535 (sem 30) fmol/mg of protein, P < 0.01 without change in the dissociation constant (KD) of the radioligand.

4. β-Adrenoceptor subtypes in lung homogenates were studied by establishing displacement curves for 125I-CYP by ICI 118551 (a selective β2-antagonist). A significant difference was seen in the proportion of β1-/β2-adrenoceptor subtypes after hypoxia (normoxic control 66 sem 2.5%, hypoxic 79 sem 2.4% β2-adrenoceptors, P < 0.01).

5. α1-Adrenoceptor number in lung membranes was measured with 125I-labelled 2-[β-(4-hydroxyphenyl)ethylaminomethyl]tetralone (125I-HEAT). No difference was seen in the number of α1-receptors in normoxia and in chronic hypoxia [Bmax.: normoxic control 48 (sem 3), hypoxic 48 (sem 5) fmol/mg of protein].

6. Treatment with salbutamol (2.5 mg/kg twice daily subcutaneously) did not reduce the number of β-adrenceptors in lung either during normoxia or in hypoxia. In spleen β-adrenoceptor number was decreased by 80% after chronic salbutamol treatment of rats in normoxia [Bmax.: normoxic control 76 (sem 19) fmol/mg of protein, treated 14 (sem 7) fmol/mg of protein, P < 0.01]. After treatment during hypoxia, however, there was no significant reduction in β-adrenoceptor number in spleen [Bmax.: hypoxic control 80 (sem 15) fmol/mg of protein, treated 77 (sem 13) fmol/mg of protein].

7. These data suggest that there is a tissue specific modulation in β-adrenoceptor numbers in response to chronic hypoxia and that their capacity for down-regulation is reduced.

This content is only available as a PDF.
You do not currently have access to this content.