Tissue specific modulation of beta-adrenoceptor number in rats with chronic hypoxia with an attenuated response to down-regulation by salbutamol.
The number of beta-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. beta-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 beta-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). Chronic hypoxia resulted in a significant increase in beta-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 less than 0.01 without change in the dissociation constant (KD) of the radioligand. beta-Adrenoceptor subtypes in lung homogenates were studied by establishing displacement curves for 125I-CYP by ICI 118551 (a selective beta 2-antagonist). A significant difference was seen in the proportion of beta 1-/beta 2-adrenoceptor subtypes after hypoxia (normoxic control 66 SEM 2.5%, hypoxic 79 SEM 2.4% beta 2-adrenoceptors, P less than 0.01). alpha 1-Adrenoceptor number in lung membranes was measured with 125I-labelled 2-[beta-(4-hydroxyphenyl)ethylaminomethyl]tetralone (125I-HEAT). No difference was seen in the number of alpha 1-receptors in normoxia and in chronic hypoxia [Bmax.: normoxic control 48 (SEM 3), hypoxic 48 (SEM 5) fmol/mg of protein].(ABSTRACT TRUNCATED AT 250 WORDS)
D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D002908:Chronic Disease; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008168:Lung / Q000032:analysis; D008297:Male; D009206:Myocardium / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000032:analysis; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000187:drug effects; D013154:Spleen / Q000032:analysis
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D000420:Albuterol