TITLE:
Serotonin uptake rates in platelets from angiotensin II-induced hypertensive mice
AUTHORS:
Preeti Singh, Terry W. Fletcher, Yicong Li, Nancy J. Rusch, Fusun Kilic
KEYWORDS:
Serotonin; Angiotensin; Platelet; Hypertension
JOURNAL NAME:
Health,
Vol.5 No.4A,
April
18,
2013
ABSTRACT: 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 the current study, we 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 concentra tions 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 blunts 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 depletes
intracellular 5-HT in platelets, an event that is
associated with reduced aggregation. The widespread use of antihypertensive
drugs that target the renin-angiotensin system suggest the potential clinical
utility of our findings and emphasize the importance of understanding the
impact of Ang II on platelet function.