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Increased beta-adrenoceptor binding capacity is associated with blunted beta-adrenoceptor-mediated cardiovascular
Insights
Essential hypertension is linked to increased beta-adrenoceptor binding capacity, particularly with age. This suggests impaired beta-adrenoceptor signaling in hypertensive individuals, affecting cardiovascular responses.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Hypertension Research
Background:
- Age and high blood pressure can blunt beta-adrenoceptor cardiovascular effects.
- Understanding the relationship between beta-adrenoceptor function and receptor density is crucial.
Purpose of the Study:
- To compare beta-adrenoceptor binding capacity and cardiac isoproterenol sensitivity in hypertensive and normotensive individuals.
- To investigate correlations between receptor binding, cardiovascular function, and hormonal activity.
Main Methods:
- Radioreceptor assay using [3H]dihydroalprenolol to determine mononuclear leucocyte beta-adrenoceptor antagonist binding capacity (Bmax) and affinity (KD).
- Measurement of cardiac isoproterenol sensitivity (CD25), plasma norepinephrine, epinephrine, and renin activity.
- Comparison between 12 essential hypertensive and 17 normotensive subjects.
Main Results:
- Higher Bmax in hypertensive patients (66.8 fmol/mg) compared to normotensive subjects (48.0 fmol/mg).
- In hypertensive patients, Bmax correlated positively with age and CD25, and negatively with plasma renin activity.
- In normotensive subjects, Bmax correlated only with CD25.
Conclusions:
- Essential hypertension is associated with an age-related increase in beta-adrenoceptor antagonist binding capacity.
- This suggests a defect in the beta-adrenoceptor effector system's membrane coupling distal to the receptor in hypertension.
- Reduced cardiac isoproterenol sensitivity and plasma renin activity are linked to increased binding capacity in hypertensive patients.
Abstract:
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.