Elevation of plasma immunoglobulin A in the spontaneously hypertensive rat.

Abstract

Prior studies describe deficiencies of T-cell-mediated immunity in the spontaneously hypertensive rat (SHR) strain of Okamoto and Aoki. This report describes an alteration of humoral immunity: elevation of the plasma concentration of immunoglobulin (Ig) A and of circulating IgA autoantibodies to single-stranded DNA, double-stranded DNA, and thyroglobulin. The increased plasma IgA levels are evident in prehypertensive SHR, hence not secondary to the hypertension, and they result mainly from increments in polymeric IgA. Plasma IgA content also varied concordantly with the level of systolic blood pressure as influenced by age (older>younger) and gender (male>female) in both the SHR and control Wistar-Kyoto rat strains. Strain differences in plasma IgG or IgM were not observed. Studies of peripheral blood lymphocytes indicate that increased production of IgA is one mechanism for the increment in plasma content. The number of blood lymphocytes capable of producing IgA in vitro in response to the mitogen lipopolysaccharide is increased in SHR. When cultured in the absence or presence of lipopolysaccharide, peripheral blood lymphocytes of SHR secrete more IgA in vitro than do cells of the control strain. No significant strain differences in biliary or renal excretion of IgA were observed. The observed alterations of IgA in the SHR either are causative factors in the development of the hypertension or are the products of an epiphenomenon in which IgA and blood pressure are affected separately, but in parallel, by causative factors related to rat strain, age, and gender.

Increased Ability of Erythrocytes to Aggregate in Spontaneously Hypertensive Rats

“…The results of the present study are in agreement with the data reported elsewhere for hypertensive humans and animals, [1][2][3][4][5][6][7][8][9][10][23][24][25][26][27] and demonstrate that plasma Fb concentration was increased in SHRs compared to the normal level of about 3 mg/mL in WKY rats. This significantly higher concentration of Fb (4 mg/mL) may be a factor in the increased RBC aggregation in homologous plasma in hypertensive rats (Results; 25).…”

“…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.…”

“…[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. According to the prevailing hypothesis, RBC aggregation is thought to be caused by nonspecific protein binding to RBCs either by molecular bridging [28][29][30] or by protein depletion [28,31] mechanisms.…”

The −174 G/C polymorphism of the interleukin-6 gene promoter and essential hypertension in an elderly Italian population

“…5 Similarly, in spontaneously hypertensive rats, a series of disturbances of the humoral and cellular immune response are present. 6 Interleukin-6 (IL-6) is an important component of the pro-inflammatory response and may be secreted by several tissues and cell types, including monocytes and macrophages, T and B-cells, fibroblasts, bone marrow stromal cells, endothelial cells, hepatocytes, smooth muscle cells, and adipose tissue. 7 IL-6 plays a key role in driving the acute inflammatory response and orchestrates the production of acute phase proteins.…”