The Effects of Beta-blockers on Endothelial Nitric Oxide Synthase Immunoreactivity in the Rat Corpus Cavernosum

Doğru, Mehmet; Aydos, Tolga Reşat; Aktuna, Zuhal; Korkusuz, Petek; Zeybek, Naciye Dilara; Görgü, Nart; Korkut, Oğuzhan; Başar, Mehmet Murad

doi:10.1016/j.urology.2009.09.025

Cited by 8 publications

(8 citation statements)

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“…With the use of [ 3 H]inulin space determination to estimate contraction and relaxation of renal glomerular vasculature, nebivolol induced relaxation of the renal glomerular microvasculature through ATP efflux with consequent stimulation of P2Y-purinoceptor-mediated NO release from glomerular endothelial cells (26). Nebivolol has also been shown to increase endothelial nitric oxide synthase (eNOS) expression and activity in various tissues (9,30,45,48).Although it is recognized that NO is involved, the renal vasodilator mechanism of nebivolol has not been delineated. In other tissues, endothelial ␤ 3 -adrenoreceptors (7,8,20,27,33,34,36,42,43), endothelial ␤ 2 -adrenoreceptors (2, 17, 35), P2Y receptors (26), and Ca 2ϩ -activated K ϩ channels (17) have been implicated in mediating its vasodilating properties.…”

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Nebivolol-induced vasodilation of renal afferent arterioles involves β₃-adrenergic receptor and nitric oxide synthase activation

Feng

Prieto

Navar

2012

American Journal of Physiology-Renal Physiology

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Nebivolol is a β(1)-adrenergic blocker that also elicits renal vasodilation and increases the glomerular filtration rate (GFR). However, its direct actions on the renal microvasculature and vasodilator mechanism have not been established. We used the in vitro blood-perfused juxtamedullary nephron technique to determine the vasodilator effects of nebivolol and to test the hypothesis that nebivolol induces vasodilation of renal afferent arterioles via an nitric oxide synthase (NOS)/nitric oxide (NO)/soluble guanylate cyclase (sGC)/cGMP pathway and the afferent arteriolar vasodilation effect may be mediated through the release of NO by activation of NOS via a β(3)-adrenoceptor-dependent mechanism. Juxtamedullary nephrons were superfused with nebivolol either alone or combined with the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or the NOS inhibitor N(ω)-nitro-l-arginine (l-NNA) or the β-blockers metoprolol (β(1)), butoxamine (β(2)), and SR59230A (β(3)). Nebivolol (100 μmol/l) markedly increased afferent and efferent arteriolar diameters by 18.9 ± 3.0 and 15.8 ± 1.8%. Pretreatment with l-NNA (1,000 μmol/l) or ODQ (10 μmol/l) decreased afferent vasodilator diameters and prevented the vasodilator effects of nebivolol (2.0 ± 0.2 and 2.4 ± 0.6%). Metoprolol did not elicit significant changes in afferent vasodilator diameters and did not prevent the effects of nebivolol to vasodilate afferent arterioles. However, treatment with SR59230A, but not butoxamine, markedly attenuated the vasodilation responses to nebivolol. Using a monoclonal antibody to β(3)-receptors revealed predominant immunostaining on vascular and glomerular endothelial cells. These data indicate that nebivolol vasodilates both afferent and efferent arterioles and that the afferent vasodilator effect is via a mechanism that is independent of β(1)-receptors but is predominantly mediated via a NOS/NO/sGC/cGMP-dependent mechanisms initiated by activation of endothelial β(3)-receptors.

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confidence: 99%

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Nebivolol-induced vasodilation of renal afferent arterioles involves β₃-adrenergic receptor and nitric oxide synthase activation

Feng

Prieto

Navar

2012

American Journal of Physiology-Renal Physiology

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“…They suggested that this positive effect was a result of the possible reduction in oxidative stress in the corpus cavernosum. Another study suggested that nebivolol had a great difference eNOS activity than other β‐blockers such as carvedilol and metoprolol; moreover, it can increase androgen receptor immunoreactivity in the endothelial layer of the corpus cavernosum (Dogru et al., ).…”

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In vitro evaluation of nebivolol effects on nonadrenergic noncholinergic responses in rabbit corpus cavernosum

et al. 2018

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The purpose of this study was to compare the effects of nebivolol on nonadrenergic noncholinergic (NANC) relaxation functions that are mediated by electric field stimulation (EFS) in rabbit corpus cavernosum smooth muscle by comparison with other beta-adrenergic receptor blockers and show the level on which its effects through nitric oxide take place. After the effects of nebivolol on the isolated corpus cavernosum tissues that were contracted through the alpha-adrenergic pathway and application of L-NAME' (N -nitro-L-arginine methyl ester) which is a competitive inhibitor of nitric oxide synthase (NOS), the changes that occurred were recorded. Following the effect on the tissue that was contracted with phenylephrine in the presence of atropine and guanethidine that was created by EFS, nebivolol and other beta-blockers were added and the changes were recorded. After receiving relaxation responses with EFS-mediated NANC, no difference was observed between the relaxation responses due to addition of nebivolol and other beta-adrenergic blockers (p > 0.05). The finding that nebivolol which has a NO-mediated relaxation effect did not have an effect on EFS-mediated NANC relaxation but created relaxation on the tissue that was contracted by phenylephrine and the effect was reversed by L-NAME, shows that its effects are on a postsynaptic level.

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“…Immunohistological procedure used in this study was described in detail previously. 24,25 In brief, 6-8 micrometer thick sections on poly-Llysine coated slides were fixed in acetone, and airdried. Anti-mouse, anti-rabbit and anti-goat HRP-DAB staining kit (Table 1) was used according to manufacturers' protocol.…”

Section: Immunohistological Evaluationmentioning

confidence: 99%

“…All sections were examined and the digital images were captured by using Leica DM6000B microscope with a DC490 digital camera (Leica, Wetzlar-Germany gen type 3, α-SMA, FN, β2M, VEGF, COX-2 and mononuclear phagocyte marker immunoreactivity by using Leica Application Suit and Qwin Plus computer image analysis system (Germany) after modifying the technique in the literature. 24,25 Maximum staining intensity was determined from the positive control tissue sections by using the image analysis system. Accordingly, each section was graded for cellular immune reaction on a scale of 0 to +++ with DAB.…”

Section: Immunohistological Evaluationmentioning

confidence: 99%

Ankaferd-Induced Early Soft Tissue Wound Healing in an Experimental Rat Model

Aktaş¹,

Er²,

Korkusuz³

et al. 2013

Turkiye Klinikleri J Med Sci

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A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Ankaferd blood stopper (ABS) is a unique standardized medicinal plant extract which has been approved in the management of post-surgical external bleeding and dental surgery in Turkey. ABS is obtained from five different plants' extracts namely Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum and Urtica dioica. The aim of this paper is to test the effects and search the underlying molecular mechanisms of ABS on the early wound healing process of extraction socket's soft tissue in a rat experimental model. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : Locally bred female 20 albino rats' right and left maxillary molars were extracted. On the right side, 0.2 mL ABS was applied on each socket, and the left side was used as the control. The animals were sacrificed on 1,2,4 and 7 th days. Indirect immunohistological procedure was performed on cryosections. Digital images were captured and quantitative image analysis was carried out for various immunohistochemical markers; collagen type 1, collagen type 3, α-smooth muscle actin, fibronectin, β 2 microglobulin, vascular endothelial growth factor and, cyclooxygenase-2. R Re es su ul lt ts s: : Immune reactivity was augmented statistically significantly (p<0.05) in various days for; collagen type 1, collagen type 3, α-smooth muscle actin, fibronectin, β 2 microglobulin, vascular endothelial growth factor, Cyclooxygenase-2 and mononuclear phagocyte marker. C Co on nc cl lu us si io on n: : ABS enhanced the number of the cells harboring the important markers of soft tissue healing as well as the biological reactivity of these cells for these molecules in the extraction sockets. Therefore this study is important for evaluating wound healing accelerating effect of ABS. K Ke ey y W Wo or rd ds s: : Wound healing; models, animal; immunohistochemistry; Ankaferd blood stopper Ö ÖZ ZE ET T A Am ma aç ç: : Ankaferd Blood Stopper (ABS) ® , Türkiye'de eksternal kanamalarda kullanılmak üzere onay almış bitki kökenli bir ekstrakttır. ABS, Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum ve Urtica dioica isimli beş bitkinin ekstraktından elde edilmektedir. Bu çal-ışmanın amacı deneysel rat modelinde ABS'nin çekim bölgesindeki yumuşak doku yara iyileşmesi üzerine olan etkinliğinin ve bunun mekanizmasının erken safhada değerlendirilmesidir. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Standart yem ile beslenmiş 20 dişi albino ratın sağ ve sol maksiller molarları çekildi. Sağ tarafta çekim sonrası boş kalan her sokete 0,2 mL ABS uygulandı, sol taraf kontrol grubu olarak bırakıldı. Ratlar 1,2,4 ve 7. günlerde sakrifiye edildi. Kryokesitler üzerinde yara iyileşmesinde görev alan kollajen tip 1, kollajen tip 3, α-düz kas aktin, fibronektin, β2 mikroglobulin, vasküler endotelyal büyüme faktörü ve siklooksijenaz-2 indirekt immünohistokimyasal yöntemlerle işaretlenerek, elde edilen veriler üzerinden sayısal analiz yapıldı. B Bu ul lg gu ul la ar r: : Kollajen tip 1, koll...

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The Effects of Beta-blockers on Endothelial Nitric Oxide Synthase Immunoreactivity in the Rat Corpus Cavernosum

Cited by 8 publications

References 26 publications

Nebivolol-induced vasodilation of renal afferent arterioles involves β₃-adrenergic receptor and nitric oxide synthase activation

Nebivolol-induced vasodilation of renal afferent arterioles involves β₃-adrenergic receptor and nitric oxide synthase activation

In vitro evaluation of nebivolol effects on nonadrenergic noncholinergic responses in rabbit corpus cavernosum

Ankaferd-Induced Early Soft Tissue Wound Healing in an Experimental Rat Model

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The Effects of Beta-blockers on Endothelial Nitric Oxide Synthase Immunoreactivity in the Rat Corpus Cavernosum

Cited by 8 publications

References 26 publications

Nebivolol-induced vasodilation of renal afferent arterioles involves β3-adrenergic receptor and nitric oxide synthase activation

Nebivolol-induced vasodilation of renal afferent arterioles involves β3-adrenergic receptor and nitric oxide synthase activation

In vitro evaluation of nebivolol effects on nonadrenergic noncholinergic responses in rabbit corpus cavernosum

Ankaferd-Induced Early Soft Tissue Wound Healing in an Experimental Rat Model

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Nebivolol-induced vasodilation of renal afferent arterioles involves β₃-adrenergic receptor and nitric oxide synthase activation

Nebivolol-induced vasodilation of renal afferent arterioles involves β₃-adrenergic receptor and nitric oxide synthase activation