title: Serotonin uptake rates in platelets from angiotensin II-induced hypertensive mice.
abstract: Angiotensin II (Ang II) is a critical component of the renin-angiotensin 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 evaluatedin vivoplatelet 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 IIin vitro. The administration of Ang II elevated systolic blood pressure, but markers of platelet activation including P-selectin andPEJon/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 vitroexposure 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 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, The University of Arkansas for Medical Sciences, Little Rock, USA.
authors.forename: Preeti
authors.initials: P
authors.lastname: Singh
authors.forename: Terry W
authors.initials: TW
authors.lastname: Fletcher
authors.forename: Yicong
authors.initials: Y
authors.lastname: Li
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Rusch
authors.forename: Fusun
authors.initials: F
authors.lastname: Kilic
keywords: Angiotensin; Hypertension; Platelet; Serotonin