Raloxifene and endothelial function in healthy postmenopausal women

Sarrel, Philip M.; Nawaz, Haq; Chan, WC; M, Fuchs; Katz, David L.

doi:10.1067/mob.2003.28

Cited by 32 publications

(30 citation statements)

References 23 publications

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“…NO protects against the development of atherosclerosis (30), and selective endothelial dysfunction is believed to be an early and pathogenic event in atherosclerosis (18). Treatment with raloxifene augmented flow-mediated vasodilatation (5,21,23,24) in menopausal women probably through increasing NO production (21). Raloxifene acutely relaxed rabbit coronary arteries (8) and improved coronary perfusion in the ischemic rat heart (15) by involving NO, and it also triggered nontranscriptional signaling pathways, leading to stimulation of endothelial NO synthase in human endothelial cells (26).…”

Section: Discussionmentioning

confidence: 99%

“…Treatment with raloxifene, a second generation SERM in healthy postmenopausal women, enhanced flow-mediated vasodilatation (5,21,23,24), increased plasma nitric oxide (NO) concentrations (21), and decreased plasma endothelin-1 levels (21). However, raloxifene therapy did not improve vascular function in postmenopausal women with coronary heart disease, whose arteries had been affected by advanced atherosclerosis (10).…”

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confidence: 99%

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Raloxifene relaxes rat intrarenal arteries by inhibiting Ca²⁺ influx

Leung

Yao²,

Lau³

et al. 2005

American Journal of Physiology-Renal Physiology

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Raloxifene may confer vascular benefits without causing estrogen-related side effects. However, its action on renal vascular circulation is unknown. This study aimed to examine the sex difference and roles of the endothelium and Ca 2ϩ channels in rat renovascular relaxation to raloxifene. On isolated intralobar renal artery rings mounted in a myograph and contracted by U-46619, concentration-relaxation curves were constructed for raloxifene and contractions to CaCl 2 were studied. Changes in intracellular Ca 2ϩ concentration levels ([Ca 2ϩ ]i) of vascular smooth muscle (VSM) were measured by fura 2 fluorescence. Raloxifene or 17␤-estradiol was equally effective in relaxing renal arteries from both sexes, with raloxifene being more potent than 17␤-estradiol. Endothelial denudation did not affect raloxifene-or 17␤-estradiol-induced relaxation. N G -nitro-L-arginine methyl ester, charybdotoxin plus apamin, indomethacin, or ICI-182, 780 did not modify the effect of raloxifene. Raloxifene caused similar relaxations in rings contracted by U-46619 and high K ϩ . Nifedipine attenuated the potency of raloxifene. Raloxifene reduced CaCl 2-induced contractions. K ϩ (80 mM) stimulated an increase in VSM [Ca 2ϩ ]i, and raloxifene attenuated this effect. Raloxifene-induced reduction of contraction and increase in VSM [Ca 2ϩ ]i were insensitive to ICI-182, 780. In summary, raloxifene causes relaxation in rat renal arteries; this effect is independent of a functional endothelium and is not mediated by ICI 182, 780-sensitive estrogen receptors. Raloxifene inhibited both contractions and VSM [Ca 2ϩ ]i in response to CaCl2, indicating that raloxifene relaxes rat renal arteries primarily through inhibiting Ca 2ϩ influx via Ca 2ϩ channels. There is little sex difference in raloxifeneinduced relaxation.17␤-estradiol; relaxation; rat renal artery SEX-RELATED DIFFERENCES IN the risk for cardiovascular diseases are generally recognized (1). In pooled analysis, observational studies report that hormone replacement therapy (HRT) reduced the primary risk of cardiovascular disease in healthy menopausal women (27). Despite this evidence, the results from recent randomized clinical trials of HRT for primary or secondary prevention of heart disease have found no overall therapeutic benefit (12,20). Instead, HRT resulted in higher incidences of strokes, heart attacks, and thrombosis (20), although the precise mechanism is unknown. Thus conventional HRT is no longer suitable for prevention of cardiovascular disease (19). Therefore, in recent years, a surge of research has focused on more selective agents that retain beneficial properties of estrogen in bone, lipids, and the cardiovascular system but with antiestrogenic activity in the breast and uterus. Such unique compounds are categorized as selective estrogen receptor modulators (SERMs). SERMs manifest selective agonistic or antagonistic activities in a multitude of estrogen target tissues. Although some SERM members have been known for decades, their tissue specificity has only recen...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Raloxifene relaxes rat intrarenal arteries by inhibiting Ca²⁺ influx

Leung

Yao²,

Lau³

et al. 2005

American Journal of Physiology-Renal Physiology

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“…Both endogenous estrogen [3] and HT [4] have been shown to improve systemic blood flow, but studies on the potential effects of SERMs on the vasculature are still being debated [5][6][7]. There have been conflicting results on whether or not raloxifene induces endothelial-mediated vasodilation in postmenopausal women [6,22,23].…”

Section: Discussionmentioning

confidence: 94%

“…There have been conflicting results on whether or not raloxifene induces endothelial-mediated vasodilation in postmenopausal women [6,22,23]. In animal models, raloxifene has been shown to acutely stimulate NO release from endothelium cells and cause vasodilation [24,25], but the results after chronic administration of raloxifene remain inconclusive [6,25].…”

Section: Discussionmentioning

confidence: 96%

“…Wassmann et al found raloxifene therapy increased NOS activity in Wistar rat models, where this treatment increased the bioavailability of nitric oxide (NO) to improve hypertension-induced endothelial dysfunction [5]. Additionally, raloxifene therapy in healthy post-menopausal women has been shown to improve flow-mediated endothelium-dependent vasodilation in the brachial artery [6] over placebo and, to an extent, comparable to HT [7].…”

Section: Introductionmentioning

confidence: 93%

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The effects of raloxifene hydrochloride on ocular hemodynamics and visual function

et al. 2008

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Local heating‐induced cutaneous vasodilation in reinnervated and noninnervated deep inferior epigastric perforator flaps

Smeele,

Martin,

van Kuijk

et al. 2023

Microsurgery

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IntroductionCutaneous vascular reactivity to local heating in free flaps has not been characterized. We aimed to assess local heating‐induced cutaneous vasodilation in reinnervated and noninnervated deep inferior epigastric perforator (DIEP) flaps.MethodsWe conducted a cross‐sectional study of 21 female patients with an uncomplicated unilateral delayed DIEP breast reconstruction at least 2 years after surgery. DIEP flaps and contralateral breasts were subjected to direct local heating, and skin blood flow was assessed using laser‐Doppler flowmetry. To evaluate sensory‐nerve‐fiber function, touch perception thresholds were assessed using a 20‐piece Touch‐test™ Sensory Evaluator, and cutaneous warm detection and heat pain thresholds were measured using a TSA‐II device.ResultsOf the participants, 10 had a reinnervated DIEP flap with a single coapted nerve (mean flap weight, 610 ± 296 g) and 11 had a noninnervated DIEP flap (mean flap weight, 613 ± 169 g). Mean age was 58 ± 11 years, mean follow‐up time was 5 ± 1 years, and mean BMI was 24 ± 3 kg/m2. DIEP flaps exhibited significantly weaker cutaneous vasodilation in response to local heating than contralateral breasts (median peak skin blood flow, 59 [25th–75th percentile, 36–71] a.u. for DIEP flaps versus 94 [74–141] a.u. for contralateral breasts; p < .001). The magnitude of the response was similar between reinnervated and noninnervated flaps (median peak skin blood flow, 55 [25th–75th percentile, 39–68] a.u. for reinnervated DIEP flaps versus 66 [36–77] a.u. for noninnervated DIEP flaps; p = .75). Of participants with reinnervated DIEP flaps, 90% perceived heat pain below the 50°C safety threshold, as compared to 36% of participants with noninnervated DIEP flaps (two‐tailed p = .02).ConclusionOur results suggest that free flap transfer causes longstanding impairment, yet not complete abolition, of both the sensory nerve‐mediated and nitric oxide‐dependent local heating‐induced cutaneous vasodilatory systems. We found no statistical evidence that flap reinnervation improves the ability to raise skin blood flow in response to local heating.

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Raloxifene and endothelial function in healthy postmenopausal women

Cited by 32 publications

References 23 publications

Raloxifene relaxes rat intrarenal arteries by inhibiting Ca²⁺ influx

Raloxifene relaxes rat intrarenal arteries by inhibiting Ca²⁺ influx

The effects of raloxifene hydrochloride on ocular hemodynamics and visual function

Local heating‐induced cutaneous vasodilation in reinnervated and noninnervated deep inferior epigastric perforator flaps

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Raloxifene and endothelial function in healthy postmenopausal women

Cited by 32 publications

References 23 publications

Raloxifene relaxes rat intrarenal arteries by inhibiting Ca2+ influx

Raloxifene relaxes rat intrarenal arteries by inhibiting Ca2+ influx

The effects of raloxifene hydrochloride on ocular hemodynamics and visual function

Local heating‐induced cutaneous vasodilation in reinnervated and noninnervated deep inferior epigastric perforator flaps

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Raloxifene relaxes rat intrarenal arteries by inhibiting Ca²⁺ influx

Raloxifene relaxes rat intrarenal arteries by inhibiting Ca²⁺ influx