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  • 1
    Online Resource
    Online Resource
    Elsevier BV ; 2018
    In:  Vascular Pharmacology Vol. 106 ( 2018-07), p. 37-45
    In: Vascular Pharmacology, Elsevier BV, Vol. 106 ( 2018-07), p. 37-45
    Type of Medium: Online Resource
    ISSN: 1537-1891
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2089264-0
    SSG: 15,3
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  • 2
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Hypertension Vol. 79, No. Suppl_1 ( 2022-09)
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 79, No. Suppl_1 ( 2022-09)
    Abstract: 5-hydroxytryptamine (5-HT, serotonin) is well-recognized to have vasodilator properties. For example, infusion of 5HT at low rates into rats decreases blood pressure acutely and chronically through reduction of total peripheral resistance. We recently showed that vasodilation in the hindquarters contributes to this fall in peripheral resistance. The hindquarter in the rat is mostly made up of skeletal muscle but also includes skin. Therefore, we hypothesized that an increase in blood flow in the skin, measured as an elevated temperature (T) in the thermoregulatory tail and paws, could contribute in part to 5-HT-induced reduction in blood pressure and hindquarters vasodilation. The temperature of thermoregulatory organs in the skin of anesthetized male, Sprague Dawley rats were measured using a Optris PI640 thermal camera. Blood pressure (from a radiotelemeter) and temperature of each paw and four locations along the tail (TL1-4) were recorded for 20 minutes before, during, and after infusion of 5-HT at a rate of 25 μg/min into the femoral vein. With this infusion protocol, the mean arterial blood pressure of rats fell over 30 mm Hg. However, the temperature of the paws (~29-32 o C) and tail (32 o at base, 25 o C at tip) were stable before and during 5-HT infusion, suggesting that flow was maintained, vs reduced, during this time. T increased during the 15-minute recovery time in all tail sections (base = from 32 o to 34 o C; tip from 23.5 o to 25.5 o C). Because the skin circulation exhibits only weak autoregulation, our results suggests that 5-HT infusion causes vasodilation of glabrous skin in the rat but without causing hyperemia. This could play a part in 5-HT induced hypotension.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2094210-2
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  • 3
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 68, No. suppl_1 ( 2016-09)
    Abstract: Obesity associated hypertension in rodent models is commonly associated with altered vascular reactivity to sympathetic neurotransmitters and inflammation-induced vascular remodeling/fibrosis. Dahl salt-sensitive (SS) rats exhibit elevated sympathetic activity and vascular remodeling. We hypothesized that diet-induced obesity in Dahl SS rats would promote hypertension, vascular dysfunction and remodeling/fibrosis. Male Dahl SS rats were placed on high fat diet (HFD, 60% kcal from fat with final concentrations of 0.33% NaCl and 1% K + , n=5) or normal-fat diet (NFD; 10% kcal from fat, 0.24% NaCl, 0.36% K + , n=5) for 24-26 weeks after weaning (3 weeks of age). Compared with NFD rats, HFD rats displayed severe hypertension (MAP, 165±4 mmHg vs 133±6 mmHg, P 〈 0.05), higher body-weight (470±6g vs 433±7g, P 〈 0.05), and hyperlipidemia (cholesterol, 211±22 mg/dl vs 138±23 mg/dl, P=0.05). HFD rats did not show significant changes in plasma levels of fasting glucose (85±5 mg/dl vs 75±5 mg/dl), insulin (2.6±0.8 ng/ml vs 2.2±1.1 ng/ml), leptin (0.77±0.18 ng/ml vs 0.44±0.06 ng/ml), or aldosterone (249±3 pg/ml vs 234±3 pg/ml) (all P 〉 0.05). HFD did not affect pressurized mesenteric arterial (~300 μm inner diameter, 60 mmHg) reactivity to norepinephrine or ATP in vitro . Pressurized mesenteric arteries from HFD rats displayed thicker walls (Ca 2+ free buffer, 40±1 μm vs 36±1 μm, P 〈 0.05), but showed slightly increased distensibility. Morphological studies did not reveal greater fibrosis in adventitia of mesenteric, intrarenal and coronary arteries from HFD rats. However, HFD induced inflammation in mesenteric perivascular adipose tissue, as shown by increased CD3 positive cell infiltration and histological evidence of fibrosis and angiogenesis. Our studies indicate that HFD in male Dahl SS rats promotes hypertension, perivascular adipose tissue inflammation and vascular remodeling, but not vascular fibrosis. Alteration of vascular contractility to sympathetic neurotransmitters, however, is not required for obesity associated hypertension in Dahl SS rats.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
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  • 4
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 79, No. Suppl_1 ( 2022-09)
    Abstract: There are considerable data to suggest an association between inflammation and cardiovascular disease, including a link between the immune system and hypertension. Our previous studies indicated an increase in the induction of proinflammatory cytokines by activated T cells cultured in media conditioned with perivascular adipose tissue (PVAT) taken from Dahl S rats on a high fat diet (HFD). Notably this effect preceded the development of hypertension in these animals. The purpose of the present studies was to test the hypothesis that high fat diet promotes inflammatory gene expression in immune cells in mesenteric PVAT and mesenteric lymph nodes (mLN) of Dahl S rats prior to the development of hypertension. To test this hypothesis, we isolated the stromal vascular fraction (SVF) from mPVAT and cells from mLN from Dahl S rats on high fat diet for 10 weeks for single cell RNA-sequencing analysis. In the mPVAT SVF we found an increase in the expression of acute inflammatory genes, including Tnfa , and genes associated with T cell chemotaxis, such as Cxcr3 and Cxcl11 . Conversely, there was also an increase in genes that negatively regulate immune response and adipokine expression in mPVAT SVF from Dahl S rats on HFD. In mLN, we found an increase in genes associated with IL-3 signaling in CD8 T cells and in genes associated with NFκB signaling in CD4 T cells (Fig. 1). Taken together, these data suggest an increase in acute inflammatory signaling in cells in mPVAT and mLN from Dahl S rats on HFD.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2094210-2
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  • 5
    In: The FASEB Journal, Wiley, Vol. 29, No. S1 ( 2015-04)
    Type of Medium: Online Resource
    ISSN: 0892-6638 , 1530-6860
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 1468876-1
    SSG: 12
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  • 6
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 68, No. suppl_1 ( 2016-09)
    Abstract: Inflammation and increased sympathetic activity contribute to hypertension. Alpha 2-adrenergic receptor (α2AR) activation decreases norepinephrine (NE) release from sympathetic nerves by inhibiting Ca 2+ channels. We hypothesized that macrophage infiltration into mesenteric arteries (MA) impairs α2AR in salt-sensitive and obesity-associated hypertensive rats. Uniphrectomized Sprague Dawley (SD) rats were given water (SHAM) or 200mg/kg DOCA (pellet, sc) and water containing 1% NaCl, 0.2% KCl (DOCA) for 4 weeks. A high fat diet (HFD, 60% kcal from fat, 0.33% NaCl, 1% K + ) or normal fat diet (NFD, 10% kcal from fat, 0.24% NaCl, 0.36% K + ) was given to a second group of SD rats for 20 weeks and to Dahl salt-sensitive (SS) rats for 24-26 weeks after weaning (3 weeks). Immunohistochemistry for CD163 (macrophage marker) was used to count macrophages in MA. Whole-cell patch clamp was used on dissociated celiac ganglion neurons to evaluate α2AR-mediated Ca 2+ current inhibition with NE (1 μM). Liposome-encapsulated clodronate (Clod) was used to deplete rats of macrophages. Plasma aldosterone levels were assessed by ELISA. Summary data is provided in Table 1. Systolic blood pressure was higher in DOCA vs SHAM and HFD vs NFD rats. Vascular macrophage number increased in DOCA vs SHAM but not in HFD vs NFD rats. NE inhibited Ca 2+ current to a greater degree in neurons of SHAM vs DOCA but not NFD vs HFD rats. Clodronate reduced vascular macrophages in all rats and preserved α2AR-mediated inhibition of Ca 2+ current in DOCA rats. HFD did not affect plasma aldosterone levels. Therefore, we conclude that macrophage-associated impairment of α2AR may only occur in states of mineralocorticoid and salt excess.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2094210-2
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  • 7
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Hypertension Vol. 79, No. Suppl_1 ( 2022-09)
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 79, No. Suppl_1 ( 2022-09)
    Abstract: Evidence supports that Antisense oligonucleotides (ASO) against the adipokine chemerin reduce the blood pressure of the normal male Sprague Dawley rat and, to a greater magnitude, the hypertensive Dahl SS rat fed a high fat diet. In the Dahl SS rat, chemerin protein concentration in white adipose tissue [mesenteric perivascular adipose tissue (Mes PVAT)] was significantly higher in females vs males. We hypothesized that female Dahl SS rats would be more dependent on chemerin for blood pressure maintenance than males because of the Mes PVAT’s proximity to blood vessels that control total peripheral resistance. Age-matched male and female Dahl SS rats on a standard chow (0.2% NaCl, 6.2% fat) diet were used. Radiotelemeters were implanted to measure blood pressure (MAP) and heart rate (bpm). Following a two-week recovery period after implantation, one week of baseline measures were collected. Knockdown of whole body chemerin was achieved by subcutaneous injections of scrambled control ASO or whole-body ASO against chemerin (both 25 mg/kg) on days 0, 7, 14, and 21. On day 23, the rats were euthanized, and samples were collected for western blot and qPCR of the chemerin gene Rarres2 . Plasma chemerin was abolished in both male and female rats given the ASO against chemerin vs that of rats receiving the control ASO. In males and females, respectively, chemerin mRNA expression (2 -ΔCT ) was reduced from 0.53 to 0.001 ± 0.002 and 0.23 to 0.001 ± 0.02 in liver, 0.05 to 0.01 ± 0.005 and 0.07 to 0.005 ± 0.02 in RP fat, and 0.09 to 0.01 ± 0.003 and 0.05 to 0.001 ± 0.02 in epididymal/uterine fat. MAP in control ASO rats showed no significant change from baseline measurements (M:137.4 ± 3.0 /F: 130.6 ± 1.5 mmHg), while males and females treated with whole-body ASO dropped by 10.7 ± 1.6 and 10.9 ± 2.1 mmHg respectively after four injections, with no significant change in heart rate. Pulse pressure also decreased by 5.6 ± 1.3 and 6.8 ± 1.3 mmHg in whole-body ASO males and females, respectively, with no significant changes from baseline in the control animals. These data suggest, contrary to our hypothesis, that chemerin plays a similar role in basal blood pressure regulation in males and females. This indicates that males and females may be equally dependent on chemerin for high fat diet-induced hypertension.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2094210-2
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  • 8
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 76, No. Suppl_1 ( 2020-09)
    Abstract: Perivascular adipose tissue (PVAT) may connect adiposity to hypertension because of its functions and proximity to blood vessels. Immune cells in adipose tissue are proposed to couple adiposity to hypertension development in a sex-specific fashion. It is unknown if sex-differences exist in PVAT’s immune community during the onset of adiposity-induced hypertension. Both sexes of the Dahl S rat strain become equally hypertensive (table) when fed a high fat (HFD) diet. We hypothesized that both sexes have similar immune cell composition in PVAT with the development and progression of HFD-induced hypertension. Male and female Dahl S rats were fed a regular (10% calories from fat; CD) diet or a HFD (60%) from weaning. Thoracic aorta PVAT (APVAT) was harvested at 10 (pre-hypertension), 17 (onset) or 24 (chronic) weeks (w) of diet. Macrophages (subtypes), neutrophils, mast, T (subtypes), B, NK cells were measured by flow cytometry. At 10 w, HFD females had 5X the number of M1-like macrophages vs HFD males. At 17 w, CD females had 10X the number of M2-like macrophages vs CD males. At 17 w and 24 w, males had greater number of CD4 (2X) and CD8 (1.5X) memory T cells vs females, independent of the diet (table). In summary, sex-differences in M1-like macrophage counts in APVAT precedes the development of HFD-induced hypertension in Dahl S rats. The progression of hypertension is associated with memory T cells in males and M2-like macrophages in females. This study is foundational to understand the sex-specific roles of these immune cells in regulating vascular tone in HFD-induced hypertension, underscoring the need for novel sex-specific anti-hypertensive immune modulators.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2094210-2
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  • 9
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Journal of Cardiovascular Pharmacology Vol. 59, No. 3 ( 2012-03), p. 207-214
    In: Journal of Cardiovascular Pharmacology, Ovid Technologies (Wolters Kluwer Health), Vol. 59, No. 3 ( 2012-03), p. 207-214
    Type of Medium: Online Resource
    ISSN: 0160-2446
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 2049700-3
    SSG: 15,3
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  • 10
    In: The FASEB Journal, Wiley, Vol. 32, No. S1 ( 2018-04)
    Type of Medium: Online Resource
    ISSN: 0892-6638 , 1530-6860
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 1468876-1
    SSG: 12
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