Increased beta-adrenoceptor binding capacity is associated with blunted beta-adrenoceptor-mediated cardiovascular responses in essential hypertension.
Age and elevated blood pressure are associated with blunted beta-adrenoceptor-mediated cardiovascular effects. To investigate a possible relationship between beta-adrenoceptor cardiovascular function and receptor density, beta-adrenoceptor binding capacity in mononuclear leucocytes and cardiac isoproterenol sensitivity were compared in 12 essential hypertensive and 17 normotensive subjects of comparable age. The bolus dose of isoproterenol which increased heart rate by 25 beats/min (CD25) as well as plasma norepinephrine, epinephrine, and renin activity were measured. In a radioreceptor assay using [3H]dihydroalprenolol, the antagonist binding capacity (Bmax) and the affinity constant (KD) of mononuclear leucocytes were determined. Bmax in patients was higher than in normotensive subjects (66.8 +/- 4.1 versus 48.0 +/- 3.8 SEM fmol/mg, p less than 0.05), and KD was identical in both groups. In hypertensive patients, Bmax correlated positively with age (r = 0.639, p less than 0.05) and CD25 (r = 0.593, p less than 0.05) and negatively with plasma renin activity (r = 0.679, p less than 0.05), while in normotensive subjects, Bmax correlated with CD25 only (r = 0.615, p less than 0.05). Thus, in patients with essential hypertension, a decrease in cardiac isoproterenol sensitivity and plasma renin activity is associated with an age-related increase in antagonist binding capacity. This suggests a defect in the membrane coupling of the beta-adrenoceptor effector system distal to the receptor recognition site in patients with essential hypertension.
R
R
Landmann
P
P
van Brummelen
F W
FW
Amann
F R
FR
Bühler
D000328:Adult; D002395:Catecholamines / Q000097:blood; D004082:Dihydroalprenolol / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D007962:Leukocytes / Q000378:metabolism; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012083:Renin / Q000097:blood
D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D012083:Renin; D007545:Isoproterenol