Non-genomic vasorelaxant effects of 17β-estradiol and progesterone in rat aorta are mediated by L-type Ca2+ current inhibition

Cairrão, Elisa; Álvarez, Ezequiel; Carvas, João Miguel; Santos-Silva, António José; Verde, Ignácio

doi:10.1038/aps.2012.4

Cited by 37 publications

(42 citation statements)

References 51 publications

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“…3). Our findings in the cerebral circulation using 3β-diol (androgen) parallel with the well established published data demonstrating TEST-, 5α-DHT, and 5β-DHT-induced vasorelaxant effects in peripheral arteries and aorta both from experimental models and human studies [14,28,84,98,122]. A common feature in the aforementioned studies is that in most, if not all cases, micromolar concentrations were required to elicit a vascular response.…”

Section: Androgens and Their Regulation Of Cerebrovascular Reactivitysupporting

confidence: 87%

Androgens and the cerebrovasculature: modulation of vascular function during normal and pathophysiological conditions

Gonzales

2013

Pflugers Arch - Eur J Physiol

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Sex steroids are commonly known for their contribution to phenotypic as well as biological reproductive sex differences mediated through classical regulation of neuroendocrine loops. However, sex steroids also have considerable impact on physiological function of non-reproductive tissues including the cerebrovasculature. Preclinical studies have shown that endogenous and exogenous administration of sex steroids significantly influences both cerebrovascular tone and brain function under normal conditions and following a pathological insult (e.g., middle cerebral artery occlusion). However, the precise mechanism(s) of how sex steroids modulate vasomotor responses and/or neurological outcomes in vivo is difficult to define since evidence based on both clinical and experimental studies has been shown to be dependent upon several variables including dose, duration of administration, presence of underlying pathologies, species, and sex. While progesterone, testosterone (TEST), and dihydrotestosterone (DHT) have all been investigated for their impact on the cerebral circulation, the effects of 17β-estradiol (E2) have been best characterized. Since recent reviews have highlighted studies reporting the actions of E2 on cerebral vascular function and health, only key points are included in this review. Conversely, less is known about the effect of androgens on the blood vessel wall, particularly in the cerebral circulation. The few studies that do address a role for androgen's modulation of cerebrovascular function under normal and pathophysiological conditions provide confounding evidence for either beneficial or detrimental effects. Therefore, the focus of this review is to highlight mechanisms associated with TEST, DHT, and its recently recognized androgen metabolite (3β-diol) on cerebrovascular function during healthy and diseased states.

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Section: Androgens and Their Regulation Of Cerebrovascular Reactivitysupporting

confidence: 87%

Androgens and the cerebrovasculature: modulation of vascular function during normal and pathophysiological conditions

Gonzales

2013

Pflugers Arch - Eur J Physiol

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“…BAYK-8644 is an LTCC activator increasing the intracellular Ca +2 concentration and inducing the contraction of vascular smooth muscle [16]. On the other hand, ventricular diastolic dysfunction is considered as the first step of the diabetic cardiomyopathy, and it is found in approximately 50% of the asymptomatic patients [17]. Because, intracellular Ca +2 homeostasis is a key factor for the connection between excitation and contraction and altered Ca +2 homeostasis in diabetes mellitus has been associated with the impairment in myocardial contractility and relaxation [18].…”

Section: • Toprak Et Al In Vitromentioning

confidence: 99%

“…The entry of Ca +2 into the cell through LTCCs results in activation of the Ca +2 release from SR. AGE cross-link breakers have been investigated to determine whether these agents can prevent the alterations in the SR-Ca +2 cycle, which lead to the cardiac dysfunction in diabetic patients [20]. The most important finding under this topic is that long-term ALT-711 treatment partially prevented the diastolic dysfunction in type-1 diabetic rats via partially improving the SR-Ca +2 move in the cardiac myocytes compared to the untreated diabetic rats [17,18].…”

Section: • Toprak Et Al In Vitromentioning

confidence: 99%

Functional Effects of Alagebrium (ALT-711)–Isolated Rat Carotid Artery

2017

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Objective: In our study, the effects of glycosylated protein cross-link breaker, alagebrium was investigated on isolated rat carotid artery using myography. Alagebrium showed vasodilator effect on carotid artery rings; particularly, this effect was significantly increased in endothelium-intact rings. Materials and Methods:To clarify the vasodilator mechanism of alagebrium, different antagonists such as N(G)-Nitro-L-arginine methyl ester (L-NAME), glibenclamide, indomethacin, metoprolol, propranolol, tetraethylammonium, and calcium channel activator BAYK-8644 were used to reverse this effect.Results: Relaxation% responses to alagebrium were more significantly increased in intact endothelium than in denuded arteries. Blocking vasodilation related to channels (K-ATP, PGI2, BKca) and receptors (ß1, ß2) did not reverse the relaxation response to alagebrium. Vasodilator response to alagebrium was only slightly decreased after L-NAME incubation and significantly decreased after BAYK-8644 incubation. Conclusion:Results of present study suggest that the mechanism of alagebrium-induced vasodilator effect may include the blockage of L-type calcium channels and partially of the nitric oxide synthase enzyme.Keywords: Alagebrium, calcium channel blockage, carotid artery, nitric oxide, vasodilatation ÖZ Amaç: Çalışmamızda, glikozile protein çapraz bağ kırıcısı olan alagebriumun sıçanlardan elde edilen karotis arter preparatları üzerindeki etkisi myograf yöntemi ile araştırılmıştır. Alagebrium karotis arter preparatlarında vazodilatör etki göstermiş ve bu etkinin özellikle endoteli sağlam damarlarda arttığı gözlenmiştir.Gereç ve Yöntem: Alagebriumun vazodilatör mekanizmasını aydınlatmak amacıyla N(G)-Nitro-L-arginine methyl ester (L-NAME), glibenklamid, indometazin, metoprolol, propranolol, tetraetilamonyum gibi antagonistler ve kalsiyum kanal aktivatörü olan BAYK 8644 bu etkiyi geri çevirmek amacıyla kullanılmıştır. Bulgular: Alagebrium % gevşeme yanıtları, endoteli sağlam damarlarda endoteli bozulmuş damarlara göre anlamlı derecede artmıştır.. Vazodilatasyon ile ilgili kanalların (KATP, PGI2, BKca) ve reseptörlerin (ß1,ß2) bloke edilmesi de alagebrium un gevşeme yanıtını geri çevirememiştir. Alagebriuma vazodilatör cevap L-NAME uygulanması ile hafif derecede azalırken BAYK-8644 uygulanması ile anlamlı derecede azalmıştır.Sonuç: Çalışmamızın sonuçları; alagebriuma bağlı vazodilatör etki mekanizmasının L-tipi kalsiyum kanal blokajı ve kısmen de nitrik oksit sentaz enzim blokajına bağlı olduğunu göstermektedir.Anahtar Kelimeler: Alagebrium, nitrik oksit, kalsiyum kanal blokajı, karotis arter, vazodilatasyon Eurasian J Med 2017; 49: 188-92

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“…Several works have reported that E 2 exerts its vasoprotective actions regulating the contractile tone of the vascular, airway and myometrium smooth muscle cells (Kisielewska et al 1996, Townsend et al 2010, Cairrão et al 2012, Holm et al 2013. These effects are mainly associated with changes in the intracellular Ca 2CC mobilization associated with cAMP and IP 3 signalling pathways (Kisielewska et al 1996, Towsend et al 2010.…”

Section: K7mentioning

confidence: 99%

Estradiol increases IP3 by a nongenomic mechanism in the smooth muscle cells from the rat oviduct

Reuquén¹,

Oróstica²,

Rojas³

et al. 2015

Reproduction

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Estradiol (E 2 ) accelerates egg transport by a nongenomic action, requiring activation of estrogen receptor (ER) and successive cAMP and IP 3 production in the rat oviduct. Furthermore, E 2 increases IP 3 production in primary cultures of oviductal smooth muscle cells. As smooth muscle cells are the mechanical effectors for the accelerated oocyte transport induced by E 2 in the oviduct, herein we determined the mechanism by which E 2 increases IP 3 in these cells. Inhibition of protein synthesis by Actinomycin D did not affect the E 2 -induced IP 3 increase, although this was blocked by the ER antagonist ICI182780 and the inhibitor of phospholipase C (PLC) ET-18-OCH 3 . Immunoelectron microscopy for ESR1 or ESR2 showed that these receptors were associated with the plasma membrane, indicating compatible localization with E 2 nongenomic actions in the smooth muscle cells. Furthermore, ESR1 but not ESR2 agonist mimicked the effect of E 2 on the IP 3 level. Finally, E 2 stimulated the activity of a protein associated with the contractile tone, calcium/ calmodulin-dependent protein kinase II (CaMKII), in the smooth muscle cells. We conclude that E 2 increases IP 3 by a nongenomic action operated by ESR1 and that involves the activation of PLC in the smooth muscle cells of the rat oviduct. This E 2 effect is associated with CaMKII activation in the smooth muscle cells, suggesting that IP 3 and CaMKII are involved in the contractile activity necessary to accelerate oviductal egg transport.Reproduction (2015) 150 331-341

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Non-genomic vasorelaxant effects of 17β-estradiol and progesterone in rat aorta are mediated by L-type Ca2+ current inhibition

Cited by 37 publications

References 51 publications

Androgens and the cerebrovasculature: modulation of vascular function during normal and pathophysiological conditions

Androgens and the cerebrovasculature: modulation of vascular function during normal and pathophysiological conditions

Functional Effects of Alagebrium (ALT-711)–Isolated Rat Carotid Artery

Estradiol increases IP3 by a nongenomic mechanism in the smooth muscle cells from the rat oviduct

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