Y‐chromosome lineage determines cardiovascular organ T‐cell infiltration in the stroke‐prone spontaneously hypertensive rat

2018 ◽  
Vol 32 (5) ◽  
pp. 2747-2756 ◽  
Author(s):  
Shanzana I. Khan ◽  
Karen L. Andrews ◽  
Kristy L. Jackson ◽  
Basimah Memon ◽  
Ann‐Maree Jefferis ◽  
...  
Keyword(s):  
T Cell ◽  
Y Chromosome ◽  
Spontaneously Hypertensive Rat ◽  
Cell Infiltration ◽  
Spontaneously Hypertensive ◽  
T Cell Infiltration ◽  
Hypertensive Rat

Vascular dysfunction in the stroke-prone spontaneously hypertensive rat is dependent on constrictor prostanoid activity and Y chromosome lineage

2018 ◽  
Vol 132 (1) ◽  
pp. 131-143 ◽  
Author(s):  
Shanzana I. Khan ◽  
Karen L. Andrews ◽  
Ann-Maree Jefferis ◽  
Garry L. Jennings ◽  
Amanda K. Sampson ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Vascular Function ◽  
Disease Risk ◽  
Spontaneously Hypertensive Rat ◽  
Vascular Dysfunction ◽  
Cardiovascular Disease Risk ◽  
Spontaneously Hypertensive ◽  
Downstream Target ◽  
Hypertensive Rat ◽  
Artery Disease

Vascular dysfunction is a hallmark of hypertension and the strongest risk factor to date for coronary artery disease. As Y chromosome lineage has emerged as one of the strongest genetic predictors of cardiovascular disease risk to date, we investigated if Y chromosome lineage modulated this important facet in the stroke-prone spontaneously hypertensive rat (SHRSP) using consomic strains. Here, we show that vascular dysfunction in the SHRSP is attributable to differential cyclooxygenase (COX) activity with nitric oxide (NO) levels playing a less significant role. Measurement of prostacyclin, the most abundant product of COX in the vasculature, confirmed the augmented COX activity in the SHRSP aorta. This was accompanied by functional impairment of the vasodilatory prostacyclin (IP) receptor, while inhibition of the thromboxane (TP) receptor significantly ameliorated vascular dysfunction in the SHRSP, suggesting this is the downstream target responsible for constrictor prostanoid activity. Importantly, Y chromosome lineage was shown to modulate vascular function in the SHRSP through influencing COX activity, prostacyclin levels and IP dysfunction. Vascular dysfunction in the renal and intrarenal arteries was also found to be prostanoid and Y chromosome dependent. Interestingly, despite no apparent differences in agonist-stimulated NO levels, basal NO levels were compromised in the SHRSP aorta, which was also Y chromosome dependent. Thus, in contrast with the widely held view that COX inhibition is deleterious for the vasculature due to inhibition of the vasodilator prostacyclin, we show that COX inhibition abolishes vascular dysfunction in three distinct vascular beds, with IP dysfunction likely being a key mechanism underlying this effect. We also delineate a novel role for Y chromosome lineage in regulating vascular function through modulation of COX and basal NO levels.

The spontaneously hypertensive rat Y chromosome produces an early testosterone rise in normotensive rats

1994 ◽  
Vol 12 (7) ◽  
pp. 769???774 ◽  
Author(s):  
Daniel L. Ely ◽  
Jessica Falvo ◽  
Gail Dunphy ◽  
Ann Caplea ◽  
Ron Salisbury ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Spontaneously Hypertensive Rat ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat

scholarly journals Spontaneously hypertensive rat: cholera toxin converts suppression to immunity through a Th2 cell-IL-4 pathway

1997 ◽  
Vol 273 (4) ◽  
pp. R1509-R1518 ◽  
Author(s):  
David W. Pascual ◽  
Michel Coste ◽  
Prosper N. Boyaka ◽  
Hiroshi Kiyono ◽  
Jerry R. McGhee
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cholera Toxin ◽  
Spontaneously Hypertensive Rat ◽  
Brown Norway ◽  
No Production ◽  
Antibody Treatment ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Ifn Γ

The spontaneously hypertensive rat (SHR) exhibits a number of T cell dysfunctions that develop concurrently with elevated blood pressure. Studies have shown a mitogen-induced lymphocyte suppression mediated in part by the production of interferon-γ (IFN-γ), which stimulated NO production by macrophages. To assess whether this immune suppression is reversible, SHR were immunized with diphtheria toxoid (DT) with or without cholera toxin (CT) as adjuvant. SHR immunized with DT only displayed weak serum immunoglobulin G (IgG) anti-DT titers, tenfold less than similarly treated normotensive Wistar-Kyoto rats (WKYR). SHR CD4+T cells failed to proliferate upon in vitro stimulation with DT. In contrast, SHR coimmunized with DT and CT showed serum IgG antibody titers similar to WKYR and Brown Norway rats. Coimmunization with CT rescued SHR CD4+T cells from suppression and supported DT- or B subunit of CT-specific proliferative responses, and these cells produced more interleukin-4 (IL-4) than IFN-γ, and anti-IFN-γ antibody treatment enhanced IL-4 production. Exogenous IL-4 increased the proliferation of antigen-specific CD4+T cells, whereas IFN-γ was inhibitory. This study shows that the adjuvant CT induces T helper 2-type responses, reversing the T cell dysfunction in the SHR.

Y chromosome locus and hypertension in the stroke prone spontaneously hypertensive rat

1995 ◽  
Vol 13 (12) ◽  
pp. 1501
Author(s):  
Anna E Dominiczak ◽  
A. O. Davidson ◽  
Andrew W. Kelman ◽  
N. Schork ◽  
John L. Reid
Keyword(s):  
Y Chromosome ◽  
Spontaneously Hypertensive Rat ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat
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