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A discrepancy between platelet alpha 2-receptor density and functional circulatory changes in hypertensives
N Mores1, M Martire, G Pistritto
1Istituto di Farmacologia, Università Cattolica del Sacro Cuore, Rome, Italy.
Insights
Essential hypertension is linked to higher platelet alpha 2-adrenoceptor density. However, these receptors do not appear to modulate cardiovascular responses to sympathetic stimuli in hypertensive individuals.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Hypertension Research
Background:
- Peripheral alpha 2-adrenoceptors play a role in regulating cardiovascular function.
- Understanding adrenoceptor differences in hypertension is crucial for targeted therapies.
Purpose of the Study:
- To compare platelet alpha 2-adrenoceptor density between normotensive and hypertensive subjects.
- To investigate the role of alpha 2-adrenoceptors in cardiovascular reactivity to sympathetic stimulation in hypertension.
Main Methods:
- Platelet alpha 2-adrenoceptor density was measured using [3H]yohimbine binding in untreated essential hypertensives and normotensive controls.
- Cardiovascular responses (mean arterial pressure, heart rate) to mental arithmetic, static handgrip, and bicycle exercise were assessed.
Main Results:
- Platelet alpha 2-adrenoceptor density was significantly higher in hypertensive subjects (314.8 fmol/mg) compared to normotensive controls (213.6 fmol/mg).
- Receptor affinity was similar between groups.
- No correlation was found between receptor density and cardiovascular changes during sympathetic stimulation tests.
Conclusions:
- Essential hypertension is associated with increased peripheral alpha 2-adrenoceptor density.
- These elevated receptors do not seem to mediate cardiovascular adaptation to sympathetic stimuli in hypertensive patients.
Abstract:
To investigate whether differences exist in peripheral alpha 2-adrenoceptors between normotensive and hypertensive subjects, we determined platelet alpha 2-adrenoceptor density in 10 (7 males) untreated essential hypertensives (mean age of 51.1 years, range of 44-59 years) and in 10 age- and sex-matched normotensive controls. Moreover, in hypertensive patients, we examined the relationship between receptor density and cardiovascular reactivity to mental arithmetic, static handgrip, and bicycle exercise, to verify the hypothesis that alpha 2-adrenoceptors might play a role in modulation of hemodynamic response to sympathetic stimuli. alpha 2-Adrenoceptor density, as calculated by binding of [3H]yohimbine to platelets, was significantly higher in essential hypertensives (314.8 +/- 38.7 fmol/mg) than in normotensive subjects (213.6 +/- 34.7 fmol/mg) (p less than 0.05), whereas receptor affinity was similar in both groups (4.0 +/- 0.5 nM hypertensives, 4.3 +/- 0.5 nM normotensives; p greater than 0.05). Mental arithmetic increased mean arterial pressure (MAP) by 21.5% from basal values and heart rate (HR) by 13.2%. During isometric exercise, MAP increased by 38.1% and HR by 24.7%, while during bicycle ergometry, mean increases in MAP and HR from baseline were of 27.2 and 54.3%, respectively. No correlation was found between platelet alpha 2-adrenoceptor density and percent changes in MAP induced by all tests, or between adrenoceptors and absolute basal and peak MAP values. Our findings suggest that in hypertensive patients, peripheral alpha 2-adrenoceptors are increased with respect to matched normotensives, but these receptors seem not to be involved in the modulation of cardiovascular adaptation to enhanced sympathetic activity.