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Platelet cyclic AMP in essential hypertensive and normotensive offspring
M M Mazeaud1, K H Le Quan Sang, M A Devynck
1Department of Pharmacology, CHU Necker, Paris, France.
Insights
Platelet cyclic adenosine monophosphate (cAMP) levels are lower in patients with essential hypertension and their normotensive relatives. This reduction in the inhibitory messenger may contribute to platelet hyper-reactivity in hypertension.
Area of Science:
- Cardiovascular Research
- Platelet Physiology
- Hypertension Pathophysiology
Background:
- Essential hypertension is linked to platelet metabolic changes and hyper-reactivity.
- Platelet activation involves cytosolic free calcium (stimulatory) and cyclic adenosine monophosphate (cAMP) (inhibitory).
- Altered cAMP metabolism may underlie platelet hyper-reactivity in hypertension.
Purpose of the Study:
- To investigate cyclic adenosine monophosphate (cAMP) levels in platelets of patients with essential hypertension.
- To compare cAMP levels in normotensive individuals with and without a family history of hypertension.
- To explore the relationship between platelet cAMP and blood pressure.
Main Methods:
- Measurement of platelet cAMP in unstimulated platelets from essential hypertensive patients and normotensive controls.
- Assessment of platelet cAMP response to prostaglandin E1 stimulation.
- Evaluation of cAMP response to phosphodiesterase inhibition using Ro 15-2041.
Main Results:
- Platelet cAMP content was significantly reduced (37.5%) in essential hypertensives.
- Normotensive subjects with a family history of hypertension also showed reduced platelet cAMP (42%).
- Platelet cAMP levels were inversely correlated with diastolic blood pressure.
Conclusions:
- Reduced platelet cAMP, the inhibitory messenger, is observed in hypertensive patients and their normotensive offspring.
- This reduction in platelet cAMP may contribute to the platelet abnormalities seen in essential hypertension.
- Findings suggest a potential role for cAMP metabolism in the pathogenesis of hypertension.
Abstract:
Essential hypertension is accompanied by several modifications to platelet metabolism suggesting hyper-reactivity to various aggregating agents. As the platelet response is mediated by both cytosolic free calcium, which is stimulatory, and cyclic (c)AMP, which is inhibitory, this hyper-reactivity may be caused by a modification in cAMP metabolism. We therefore determined cAMP in unstimulated platelets from 19 patients with essential hypertension and 27 age-matched normotensive subjects, nine with and 19 without a family history of hypertension. The platelet cAMP content was reduced in the essential hypertensives and in the normotensives with a positive family history by 37.5% and 42%, respectively (P less than 0.001 for both). Platelet cAMP was inversely correlated with diastolic blood pressure (P = 0.036). After prostaglandin (PG) E1 stimulation, the platelet cAMP content remained lower in the patients with essential hypertension than in the normotensive subjects, whatever their hypertensive heredity. The rises in cAMP caused by inhibition of phosphodiesterase by 7-bromo-1,5-dihydro-3,6-dimethylimidazo-[2,1-b]quinazolin-2[ 3H]-one (Ro 15-2041) were similar in the three groups. These results indicate that cAMP, the platelet inhibitory messenger, is reduced in hypertensive patients and in their normotensive offspring and may affect the various platelet abnormalities previously described in this disease.