Angiotensin II (Ang II) is a
critical component of the reninangiotensin system that contributes to
hypertension. Although platelets in blood from hypertensive subjects have an
abnormal biological profile, it is unclear if circulating Ang II influences
platelet aggregation or thrombus formation.
One of the
abnormalities presented to the platelets during hypertension is an elevated plasma
concentration of serotonin (5-HT) caused by reduced 5-HT uptake secondary
to loss of the 5-HT transporter (SERT) on the platelet plasma membrane. In this
study, the authors evaluated in vivo platelet
function after 7 days of subcutaneous Ang II infusion to establish hypertension
in mice and additionally assessed the biology of isolated platelets exposed to
Ang II in vitro.
The administration
of Ang II elevated systolic blood pressure, but markers of platelet activation
including P-selectin and PEJon/A staining were not changed.
However, the aggregation response to collagen was reduced in isolated platelets
from Ang II-infused mice, which also showed reduced 5-HT uptake by SERT. In vitro exposure
of isolated platelets to Ang II also resulted in a loss of surface SERT
associated with a reduced aggregation response to collagen. These abnormalities
were reversed by increasing concentrations of the Ang II receptor antagonist,
valsartan. Interestingly, SERT KO mice failed to fully develop hypertension in
response to Ang II infusion and isolated platelets from these animals were
insensitive to the anti-aggregatory influence of Ang II. Thus, Ang II blunted
the aggregation responses of platelets and the mechanism underlying this action
may involve a loss of SERT on the platelet plasma membrane. The latter
event depleted intracellular 5-HT in platelets, an event that was
associated with reduced aggregation.
In conclusion, the
widespread use of antihypertensive drugs that targeted the renin-angiotensin
system suggested the potential clinical utility of the findings and emphasized
the importance of understanding the impact of Ang II on platelet function.
Article by Preeti
Singh, et al, from The University of Arkansas for Medical Sciences, Little
Rock, USA .
Full access: http://mrw.so/39Ejdo
Image by bk_hmd, from Flickr-cc.
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