Greater fractalkine expression in mesenteric arteries of female spontaneously hypertensive rats compared with males

Sullivan, Jennifer C.; Pardieck, Jennifer; Doran, Derek E.; Zhang, Yan; She, Jin Xiong; Pollock, Jennifer S.

doi:10.1152/ajpheart.01093.2008

Cited by 10 publications

(12 citation statements)

References 40 publications

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“…consistent with our previous publications in SHR and normotensive F344 Brown-Norway rats (Sullivan et al , 2009). To further determine if sex/strain differences in PE-induced contraction were due to differences in the contractile machinery, we assessed KCl-induced contraction as well.…”

Section: Discussionsupporting

confidence: 94%

“…There were no sex differences in either strain in PE‐included constriction or the impact of l ‐NAME, consistent with our previous publications in SHR and normotensive F344 Brown‐Norway rats (Sullivan et al. , ).…”

Section: Discussionsupporting

confidence: 92%

“…In contrast to our findings, relaxation to ACh in norepinephrine‐precontracted mesenteric rings was attenuated in both female and male SHR compared to WKY (Kauser and Rubanyi ), however, the lack of a sex difference in ACh‐induced relaxation is consistent with previous publications from our group (Sullivan et al. , ). Others have shown that the relative role of NO in the endothelium‐dependent and independent relaxation was higher in female than in male SHR.…”

Section: Discussionsupporting

confidence: 90%

“…Therefore, our data suggest a shift in the balance of these dilatory pathways to maintain relaxation with hypertension, such that the NOS-mediating component is increased, potentially in response to increases in blood pressure to help limit further increases in pressure and vascular dysfunction. In contrast to our findings, relaxation to ACh in norepinephrine-precontracted mesenteric rings was attenuated in both female and male SHR compared to WKY (Kauser and Rubanyi 1995), however, the lack of a sex difference in ACh-induced relaxation is consistent with previous publications from our group (Sullivan et al , 2009. Others have shown that the relative role of NO in the endothelium-dependent and independent relaxation was higher in female than in male SHR.…”

Section: Discussionsupporting

confidence: 84%

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Sex-specific alterations in NOS regulation of vascular function in aorta and mesenteric arteries from spontaneously hypertensive rats compared to Wistar Kyoto rats

et al. 2014

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The present study tested the hypothesis that spontaneously hypertensive rats (SHR) have impaired nitric oxide synthase (NOS)‐mediated regulation of vascular function versus Wistar‐Kyoto rats (WKY). Aorta and small mesenteric arteries were studied from male and female SHR (M SHR and F SHR) and WKY (M WKY and F WKY). Phenylephrine (PE)‐induced vasoconstriction was greater in aorta of M SHR versus all others (P < 0.05); there were neither sex nor strain differences in PE contraction in mesenteric arteries. The NOS inhibitor l‐Nitro‐Arginine Methyl Ester (l‐NAME) increased PE‐induced vasoconstriction in all rats, although the increase was the least in male SHR (P < 0.05), revealing a blunted vasoconstrictor buffering capacity of NOS. l‐NAME increased sensitivity to PE‐induced constriction only in mesenteric arteries of SHR, although, the maximal percent increase in contraction was comparable among groups. ACh‐induced relaxation was also less in aorta from M SHR versus all others (P < 0.05). ACh relaxation was comparable among groups in mesenteric arteries, although SHR exhibited a greater NOS component to ACh‐induced relaxation than WKY. To gain mechanistic insight into sex and strain differences in vascular function, NOS activity and NOS3 protein expression were measured. Aortic NOS activity was comparable between groups and M SHR had greater NOS3 expression than M WKY. In contrast, although vascular function was largely maintained in mesenteric arteries of SHR, NOS activity was less in SHR versus WKY. In conclusion, M SHR exhibit a decrease in NOS regulation of vascular function compared to F SHR and WKY, although this is not mediated by decreases in NOS activity and/or expression.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 84%

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Sex-specific alterations in NOS regulation of vascular function in aorta and mesenteric arteries from spontaneously hypertensive rats compared to Wistar Kyoto rats

et al. 2014

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“…In contrast, high concentrations of TGF-β with low IL-6 levels drives Treg formation. Our group published that excretion of TGF-β and TNF-α are greater in female SHR compared to males 93 and more recently that female SHR have more IL-10 + cells in their kidneys while males have more IL-6 + and IL-17 + renal cells 68 . These findings were confirmed using immunohistochemical analysis of key cytokines involved in T cell differentiation in male and female SHR: IL-17, IL-23, and TGF-β.…”

Section: Potential Mechanisms Driving Sex Differences In T Cellsmentioning

confidence: 95%

Sex Differences in T Cells in Hypertension

Tipton

Sullivan

2014

Clinical Therapeutics

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Purpose Hypertension is a major risk factor for the development of cardiovascular disease, stroke and end-organ damage. There is a sex difference in blood pressure (BP) that begins in adolescence and continues into adulthood, where men have a higher prevalence of hypertension compared to women until the sixth decade of life. Less than 50% of hypertensive adults in the United States taking medication manage to control their BP to recommended levels using current therapeutic options, and women are more likely than men to have uncontrolled high BP. This is despite the fact that more women compared to men are aware that they have hypertension and women are more likely to seek treatment for the disease. Novel therapeutic targets need to be identified in both sexes to increase the percentage of hypertensive individuals with controlled BP. The purpose of this article is to review the available literature on the role of T cells in BP control in both sexes, and the potential therapeutic application/implications of targeting immune cells in hypertension. Methods A search of PUBMED was conducted to determine the impact of sex and gender on T cell-mediated control of BP. The search terms included sex, gender, estrogen, testosterone, inflammation, T cells, T regulatory cells, Th17 cells, hypertension and blood pressure. Additional data were included from our laboratory examining cytokine expression in the kidney of male and female SHR and differential genes expression in both the renal cortex and mesenteric arterial bed of male and female SHR. Findings There is a growing basic science literature regarding the role of T cells in the pathogenesis of hypertension and BP control, however, the majority of this literature has been performed exclusively in males despite the fact that both men and women develop hypertension. There is increasing evidence that while T cells also mediate BP in females, there are distinct differences in both the T cell profile and the functional impact of “male” vs. “female” T cells on cardiovascular health, although more work is needed to better define the relative impact of different T cell subtypes on BP in both sexes. Implications The challenge now is to fully understand the molecular mechanisms by which the immune system regulates BP and how the different components of the immune system interact so that specific mechanisms can be targeted therapeutically without compromising natural immune defenses.

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