Increased Erythrocyte Aggregation in Spontaneously Hypertensive Rats

Abstract

Alterations of red blood cell (RBC) aggregation and plasma viscosity are major contributors to the changes in blood rheologic properties that cause an increase in peripheral vascular resistance during the development of hypertension. Although basic research and clinical study have provided considerable understanding of the pathophysiology of hypertension, the objective of this study was to determine whether an increase in RBC aggregability and plasma viscosity precede or accompany the development of high arterial blood pressure. To address this question, RBC aggregation and plasma viscosity were studied in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) at 3 and 12 weeks of age. The plasma concentrations of fibrinogen and fibronectin (FN) were also analyzed in both age groups. RBC aggregability and plasma viscosity were increased in both young and mature SHR compared to age-matched normotensive WKY rats. Mean arterial blood pressure and diastolic pressures were increased in mature hypertensive rats, whereas in young SHR only diastolic pressure was elevated significantly. The concentration of fibrinogen was higher only in the mature hypertensive rats, whereas plasma FN content was greater in both 3- and 12-week-old SHR compared to age-matched WKY. These results show the existence of increased RBC aggregability and plasma hyperviscosity not only during the established phase of hypertension, but also during the early stage of hypertension development, when mean arterial blood pressure is not yet significantly elevated in the genetically hypertensive rat model. These changes may be related to significant increase in the plasma protein FN, which occurs at the same time as the RBC aggregability and plasma viscosity changes. These results may increase attention to changes in the rheologic properties and to the mechanisms involved in these processes in the early stages of hypertension development.

Fibrinogen-Induced Increased Pial Venular Permeability in Mice

“…Increased blood concentration of Fg results in an increase of blood viscosity (Lominadze et al, 1998) and therefore an increase in blood flow shear stress (Chien et al, 1966). This contributes to an activation of ECs expressing and/or activating various integrins and adhesion molecules including ICAM-1 (Springer, 1990), a well-known Fg receptor (Plow et al, 2000).…”

“…During inflammation, overexpression of interleukin-1 and interleukin-6 leads to an increased blood content of Fg (Nakamura et al, 1996). Elevated blood level of Fg is a biomarker of inflammation and high risk factor for many cardiovascular (Danesh et al, 2005) and cerebrovascular disorders (del Zoppo et al, 2009) such as hypertension (Lominadze et al, 1998) and stroke (Eidelman and Hennekens, 2003). While normal blood concentration of Fg is about 2 mg/mL (Lominadze et al, 2010), during hypertension it reaches 4 mg/mL (Lominadze et al, 1998) and 3.6 mg/mL after ischemic stroke in humans (Eidelman and Hennekens, 2003).…”

Increased Ability of Erythrocytes to Aggregate in Spontaneously Hypertensive Rats

“…[25] The washed cells were suspended in homologous plasma with a volume ratio of 1 part of erythrocytes to 200 parts of plasma. An assessment of plasma-induced RBC aggregation was done under static conditions by direct visualization of the process.…”

“…Alterations of major determinants of the blood's rheological properties observed in hypertensive disease include increased viscosity of blood [23,24] and plasma, [23][24][25] increased hematocrit [24,25] and increased levels of high molecular weight plasma proteins including fibronectin, [25] immunoglobulin-A [26] and particularly fibrinogen (Fb), [3] which are the major determinants of plasma viscosity. Furthermore, it has been shown that RBC aggregation, which has the most significant effect on blood rheological properties, is increased during hypertension.…”

“…Furthermore, it has been shown that RBC aggregation, which has the most significant effect on blood rheological properties, is increased during hypertension. [23][24][25][26][27] Among the plasma adhesion proteins having an effect on RBC aggregation, Fb has been identified as having the most pronounced effect. [3,23,[26][27][28] While the relationship between plasma proteins and RBC aggregation is established, the mechanism of action is still unclear.…”