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Serotonin Uptake Rates in Platelets from Angiotensin II-Induced Hypertensive Mice

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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