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  • 1
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 27, No. 11 ( 2007-11), p. 2348-2354
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 27, No. 11 ( 2007-11), p. 2348-2354
    Abstract: The present study shows enhanced dilations of coronary arterioles and brachial arteries in obese hypertensive patients, implying an important functional adaptation, such as an increased sensitivity to NO of coronary and peripheral arterial vessels, to the simultaneous presence of obesity and hypertension.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 1494427-3
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  • 2
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 116, No. suppl_16 ( 2007-10-16)
    Abstract: Increased body weight and elevated blood pressure could lead to the development of hyperdynamic circulation requiring increased coronary blood flow. Thus, we aimed to characterize the effects of simultaneous presence of obesity and hypertension on the dilator function of human coronary arterioles. Agonist-induced dilations were assessed in pressurized coronary arterioles isolated from the right atrial appendages of patients (N=38), that underwent cardiac surgery. There were no significant differences in bradykinin (BK)-induced and the nitric oxide (NO)-donor, sodium-nitroprusside (SNP)-evoked dilations of coronary arterioles between normotensive and hypertensive lean patients. In contrast, in the obese, normotensive patients BK- and SNP-induced dilations were reduced (BK, 10 −7 M, lean:90±4%, obese:64±7%; SNP, 10 −6 M, lean:89±7%, obese:76±5%), whereas in the obese, hypertensive patients BK- and SNP-induced dilations were significantly enhanced, when compared to lean subjects (BK, 10 −7 M, lean:71±7%, obese:85±3%; SNP, 10 −6 M, lean:60±6%, obese:83±2%). Correspondingly, in hypertensive individuals, but not in those of normotensives, a positive correlation was found between body mass index (BMI) and bradykinin-induced ( P =0.03, r=0.46), and also SNP-evoked ( P 〈 0.03, r=0.44) coronary dilations. To correlate coronary responses to those of peripheral vessels, in an additional 55 hypertensive patients flow-mediated (FMD) and nitroglycerin (NTG)-induced dilations were assessed by high-resolution ultrasound. In obese, hypertensive individuals both FMD and NTG-induced dilations were significantly greater (FMD:6.2±0.7%, NTG:17.2±0.9%), than in lean hypertensive patients (FMD:3.7±0.6%, NTG:13.6±1.1%). Correspondingly, both FMD and NTG-induced dilations were positively correlated with BMI, ( P =0.02, r=0.31, P =0.03, r=0.29, respectively). These findings are the first to show that in humans obesity may lead to activation of an adaptive vascular mechanisms in hypertension, such as an increased sensitivity to NO, enhancing the dilator function of coronary and peripheral arterial vessels.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 1466401-X
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  • 3
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 99, No. 5 ( 2006-09)
    Abstract: Based on findings of experimental models of diabetes mellitus (DM) showing increased expression of vascular cyclooxygenase-2 (COX-2), we hypothesized that in patients with DM changes in COX-2–dependent prostaglandin synthesis affect vasomotor responses of coronary arterioles. Arterioles were dissected from the right atrial appendages obtained at the time of cardiac surgery of patient with DM(+) or without documented diabetes DM(−). Isolated arterioles (89±15 μm in diameter) were cannulated and pressurized (at 80 mm Hg), and changes in diameter were measured with video microscopy. After spontaneous tone developed [DM(−): 32±7%; DM(+): 37±5%; P =NS], arteriolar responses to bradykinin were investigated. Dilations to bradykinin (0.1 nmol/L to 1 μmol/L) were significantly ( P 〈 0.05) greater in DM(+) than DM(−) patients (10 nmol/L: 77±10% versus 38±14%). In both groups, dilations were similar to the NO-donor, sodium nitroprusside. In arterioles of DM(+), but not those of DM(−), patients’ bradykinin-induced dilations were reduced by the nonselective COX inhibitor indomethacin or by the selective COX-2 inhibitor NS-398 (DM(+) at 10 nmol/L: to 20±4% and 29±7%, respectively). Correspondingly, a marked COX-2 immunostaining was detected in coronary arterioles of DM(+), but not in those of DM(−) patients. We conclude that in coronary arterioles of diabetic patients bradykinin induces enhanced COX-2–derived prostaglandin-mediated dilation. These findings are the first to show that in humans diabetes mellitus increases COX-2 expression and dilator prostaglandin synthesis in coronary arterioles, which may serve to increase dilator capacity and maintain adequate perfusion of cardiac tissues.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2006
    detail.hit.zdb_id: 1467838-X
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  • 4
    Online Resource
    Online Resource
    American Physiological Society ; 2008
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 294, No. 6 ( 2008-06), p. H2558-H2564
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 294, No. 6 ( 2008-06), p. H2558-H2564
    Abstract: The impact of obesity on nitric oxide (NO)-mediated coronary microvascular responses is poorly understood. Thus NO-mediated vasomotor responses were investigated in pressurized coronary arterioles (∼100 μm) isolated from lean (on normal diet) and obese (fed with 60% of saturated fat) rats. We found that dilations to acetylcholine (ACh) were not significantly different in obese and lean rats (lean, 83 ± 4%; and obese, 85 ± 3% at 1 μM), yet the inhibition of NO synthesis with N ω -nitro-l-arginine methyl ester reduced ACh-induced dilations only in vessels of lean controls. The presence of the soluble guanylate cyclase (sGC) inhibitor oxadiazolo-quinoxaline (ODQ) elicited a similar reduction in ACh-induced dilations in the two groups of vessels (lean, 60 ± 11%; and obese, 57 ± 3%). Dilations to NO donors, sodium nitroprusside (SNP), and diethylenetriamine (DETA)-NONOate were enhanced in coronary arterioles of obese compared with lean control rats (lean, 63 ± 6% and 51 ± 5%; and obese, 78 ± 5% and 70 ± 5%, respectively, at 1 μM), whereas dilations to 8-bromo-cGMP were not different in the two groups. In the presence of ODQ, both SNP and DETA-NONOate-induced dilations were reduced to a similar level in lean and obese rats. Moreover, SNP-stimulated cGMP immunoreactivity in coronary arterioles and also cGMP levels in carotid arteries were enhanced in obese rats, whereas the protein expression of endothelial NOS and the sGC β 1 -subunit were not different in the two groups. Collectively, these findings suggest that in coronary arterioles of obese rats, the increased activity of sGC leads to an enhanced sensitivity to NO, which may contribute to the maintenance of NO-mediated dilations and coronary perfusion in obesity.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2008
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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  • 5
    In: The FASEB Journal, Wiley, Vol. 21, No. 6 ( 2007-01)
    Type of Medium: Online Resource
    ISSN: 0892-6638 , 1530-6860
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2007
    detail.hit.zdb_id: 1468876-1
    SSG: 12
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