Effect of estrogen on flow-induced dilation in NO deficiency: role of prostaglandins and EDHF

Huang, An; Wu, Yuming; Sun, Dong; Koller, Ákos; Kaley, Gabor

doi:10.1152/jappl.2001.91.6.2561

Cited by 52 publications

(67 citation statements)

References 27 publications

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“…The contribution of each of these factors to endothelium-dependent vasodilation varies across vascular beds and also according to what agent is used to stimulate the endothelium. In general, the endothelium predominantly releases NO in large arteries (28) such as carotid arteries (29), while the contribution of EDHF is more important in smaller resistance arteries (30) such as the mesenteric arteries (31), and arterioles (32). The involvement of prostanoid (mainly prostacyclin) in the regulation of vascular tone has not been widely reported and is often overlooked due to experimental designs in which cyclooxygenase blockers were present since the onset of experimentation.…”

Section: Discussionmentioning

confidence: 99%

Endothelial mediators of 17ß-estradiol-induced coronary vasodilation in the isolated rat heart

Santos

Abreu

Bissoli

et al. 2004

Braz J Med Biol Res

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The present study was designed to determine relaxation in response to 17ß-estradiol by isolated perfused hearts from intact normotensive male and female rats as well as the contribution of endothelium and its relaxing factors to this action. Baseline coronary perfusion pressure was determined and the vasoactive effects of 17ß-estradiol (10 µM) were assessed by in bolus administration before and after endothelium denudation by infusion of 0.25 µM sodium deoxycholate or perfusion with 100 µM L-NAME, 2.8 µM indomethacin, 0.75 µM clotrimazole, 100 µM L-NAME plus 2.8 µM indomethacin, and 100 µM L-NAME plus 0.75 µM clotrimazole. Baseline coronary perfusion pressure differed significantly between males (84 ± 2 mmHg, N = 61) and females (102 ± 2 mmHg, N = 61). Bolus injection of 10 µM 17ß-estradiol elicited a transient relaxing response in all groups, which was greater in coronary beds from females. For both sexes, the relaxing response to 17ß-estradiol was at least in part endothelium-dependent. In the presence of the nitric oxide synthase inhibitor L-NAME, the relaxing response to 17ß-estradiol was reduced only in females. Nevertheless, in the presence of indomethacin, a cyclooxygenase inhibitor, or clotrimazole, a cytochrome P450 inhibitor, the 17ß-estradiol response was significantly reduced in both groups. In addition, combined treatment with L-NAME plus indomethacin or L-NAME plus clotrimazole also reduced the 17ß-estradiol response in both groups. These results indicate the importance of prostacyclin and endothelium-derived hyperpolarizing factor in the relaxing response to 17ß-estradiol. 17ß-estradiol-induced relaxation may play an important role in the regulation of coronary tone and this may be one of the reasons why estrogen replacement therapy reduces the risk of coronary heart disease in postmenopausal women.

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Section: Discussionmentioning

confidence: 99%

Endothelial mediators of 17ß-estradiol-induced coronary vasodilation in the isolated rat heart

Santos

Abreu

Bissoli

et al. 2004

Braz J Med Biol Res

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“…Indeed, there is evidence hinting at a link between estrogen and EDHF activity. EDHF-mediated responses to ACh, 9,27 shear stress, 28 ADP, 29 or Ca 2ϩ ionophore 30 are all reduced by ovariectomy; however, E2 is known to target several signal transduction pathways in the vasculature, including the muscarinic receptor M2 and M3 pathways, 31 which suggests that alternative mechanisms may be responsible at least for the changes in EDHF activity in response to ACh. It is unlikely that this latter mechanism is at play in the present study, because BK also produced relaxation of dKO arteries that persisted in the presence of NOS and COX inhibition, which demonstrates that EDHFmediated relaxation is a general phenomenon of these arteries and is not due to an increase in sensitivity to ACh.…”

Section: Male Mice Exhibit Dramatically Less Edhf Activity Than Femalmentioning

confidence: 99%

Investigation of Vascular Responses in Endothelial Nitric Oxide Synthase/Cyclooxygenase-1 Double-Knockout Mice

et al. 2005

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Background-Endothelium-dependent dilatation is mediated by 3 principal vasodilators: nitric oxide (NO), prostacyclin (PGI 2 ), and endothelium-derived hyperpolarizing factor (EDHF). To determine the relative contribution of these factors in endothelium-dependent relaxation, we have generated mice in which the enzymes required for endothelial NO and PGI 2 production, endothelial NO synthase (eNOS) and cyclooxygenase-1 (COX-1), respectively, have been disrupted (eNOS Ϫ/Ϫ and COX-1 Ϫ/Ϫ mice). Methods and Results-In female mice, the absence of eNOS and COX-1 had no effect on mean arterial blood pressure (BP), whereas BP was significantly elevated in eNOS Ϫ/Ϫ /COX-1 Ϫ/Ϫ males compared with wild-type controls. Additionally, endothelium-dependent relaxation remained intact in the resistance vessels of female mice and was associated with vascular smooth muscle hyperpolarization; however, these responses were profoundly suppressed in arteries of male eNOS Ϫ/Ϫ /COX-1 Ϫ/Ϫ animals. Similarly, the endothelium-dependent vasodilator bradykinin produced dose-dependent hypotension in female eNOS Ϫ/Ϫ /COX-1 Ϫ/Ϫ animals in vivo but had no effect on BP in male mice. Conclusions-These studies indicate that EDHF is the predominant endothelium-derived relaxing factor in female mice, whereas NO and PGI 2 are the predominant mediators in male mice. Moreover, the gender-specific prevalence of EDHF appears to underlie the protection of female eNOS

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“…Local arteriolar and ascending vasodilatation results in an increased blood flow through the upstream resistance arteries. The resulting increase in wall shear stress triggers release of endothelium-derived vasodilators, such as nitric oxide (NO), prostacyclin, bradykinin, and endothelium-derived hyperpolarizing factor (22,24). The increase in luminal diameter tends to restore wall shear stress and leads, together with the increase in transmural pressure, to an elevation of circumferential wall stress and of the strain on the resistance arterial smooth muscle cells (SMC).…”

Section: Flow-induced Vasodilatation and Flow-induced Remodeling Of Rmentioning

confidence: 99%

Toward functional genomics of flow-induced outward remodeling of resistance arteries

Mey

Schiffers

Hilgers

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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.-In resistance-sized arteries, a chronic increase in blood flow leads to increases in arterial structural luminal diameter and arterial wall mass. In this review, we summarize recent evidence that outward remodeling of resistance arteries 1) can help maintain and restore tissue perfusion, 2) is not intimately related to flowinduced vasodilatation, 3) involves transient dedifferentiation and turnover of arterial smooth muscle cells, and 4) is preceded by increased expression of matricellular proteins, which have been shown to promote disassembly of focal adhesion sites. Studies of experimental and physiological resistance artery remodeling involving differential gene expression analyses and the use of knockout and transgenic mouse models can help unravel the mechanisms of outward remodeling.flow-induced vasodilatation; matricellular protein; gene expression microarray analysis IN ARTERIES, TRANSMURAL PRESSURE and blood flow influence wall thickness and structural luminal diameter (13,16,28,29,49). Mathematical modeling, cell and molecular biological approaches, and experiments in genetically modified animals are beginning to shed light on the mechanisms that underlie these arterial remodeling responses. Here, we summarize recent observations concerning flow-induced outward remodeling of resistance arteries. Exploration of this type of arterial structural response might lead to pharmacological treatments to 1) improve collateral perfusion and 2) reverse the inward arterial remodeling in essential hypertension. TERMINOLOGYRemodeling is frequently used to describe any alteration of arterial structure. In agreement with others (4, 38), we find it useful to note the differences among several types of arterial remodeling: 1) neointima formation, 2) alteration of the arterial structural luminal diameter (outward or inward), and 3) alteration of tunica media mass (hypertrophic, eutrophic, and hypotrophic). Although this classification is helpful, it also highlights gaps in current knowledge, such as the manner in which media, adventitia, and ultrastructural wall components, such as extracellular matrix, focal adhesion sites, and cytoskeleton, determine the diameter. Arterial structural diameter refers to the maximally dilated diameter and results from the elastic properties of the arterial wall. The diameter of an arterial segment in vivo obviously depends on this structural diameter and on the degree of vasomotor tone or smooth muscle contractile activity.Resistance arteries are small (300 -100 m diameter) muscular arteries that are situated between large elastic conduit arteries and arterioles. In contrast to the large arteries, resistance arteries 1) not only respond to, but also influence, local mean arterial pressure and blood flow, 2) rarely, if ever, develop a neointima, and 3) do not display hypertrophy but, rather, exhibit inward eutrophic remodeling during chronic hypertension (37). In resistance arteries, circumferential wall stress and wall shear stress are maintained at higher values than in arterioles (43)...

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Effect of estrogen on flow-induced dilation in NO deficiency: role of prostaglandins and EDHF

Cited by 52 publications

References 27 publications

Endothelial mediators of 17ß-estradiol-induced coronary vasodilation in the isolated rat heart

Endothelial mediators of 17ß-estradiol-induced coronary vasodilation in the isolated rat heart

Investigation of Vascular Responses in Endothelial Nitric Oxide Synthase/Cyclooxygenase-1 Double-Knockout Mice

Toward functional genomics of flow-induced outward remodeling of resistance arteries

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