Nitric oxide synthase/K+ channel cascade triggers the adenosine A2B receptor-sensitive renal vasodilation in female rats

El‐Gowelli, Hanan M.; El‐Gowilly, Sahar M.; Elsalakawy, Lamia K.; El‐Mas, Mahmoud M.

doi:10.1016/j.ejphar.2013.01.049

Cited by 15 publications

(17 citation statements)

References 49 publications

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“…5). Previous studies suggested a role for PKA, the NO signaling pathway, and potassium (K 1 ) channels in mediating adenosine-mediated vasorelaxation (Mi et al, 2008;Sanjani et al, 2011;El-Gowelli et al, 2013;Hein et al, 2013). Our data showed that PKA inhibition caused a rightward shift of the CRC, resulting in a decrease in relaxation to NECA.…”

Section: Adenosine Receptors and The Pudendal Arterysupporting

confidence: 46%

“…Adenosine binds to a family of four P1 G proteincoupled AR subtypes: A 1 , A 2A , A 2B , and A 3 . Vascular studies from our laboratory and others have demonstrated that, whereas the activation of the A 1 AR and A 3 AR results in vasoconstriction, the activation of the A 2A AR and A 2B AR results in vasodilation (Tawfik et al, 2005;Ansari et al, 2007;Nayeem et al, 2008;El-Awady et al, 2011;Sanjani et al, 2011;El-Gowelli et al, 2013;Hein et al, 2013;Kunduri et al, 2013;Teng et al, 2013). The different contribution of each AR subtype to the physiology or pathophysiology of erection has been studied in the corpus cavernosum (CC).…”

Section: Introductionmentioning

confidence: 99%

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Role of Adenosine Receptor(s) in the Control of Vascular Tone in the Mouse Pudendal Artery

Labazi

Tilley

Ledent

et al. 2016

The Journal of Pharmacology and Experimental Therapeutics

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Activation of adenosine receptors (ARs) has been implicated in the modulation of renal and cardiovascular systems, as well as erectile functions. Recent studies suggest that adenosinemediated regulation of erectile function is mainly mediated through A 2B AR activation. However, no studies have been conducted to determine the contribution of AR subtype in the regulation of the vascular tone of the pudendal artery (PA), the major artery supplying and controlling blood flow to the penis. Our aim was to characterize the contribution of AR subtypes and identify signaling mechanisms involved in adenosine-mediated vascular tone regulation in the PA. We used a DMT wire myograph for muscle tension measurements in isolated PAs from wild-type, A 2A AR knockout, A 2B AR knockout, and A 2A /A 2B AR double-knockout mice. Real-time reverse transcription-polymerase chain reaction was used to determine the expression of the AR subtypes. Data from our pharmacologic and genetic approaches suggest that AR activation-mediated vasodilation in the PA is mediated by both the A 2A AR and A 2B AR, whereas neither the A 1 AR nor A 3 AR play a role in vascular tone regulation of the PA. In addition, we showed that A 2A AR-and A 2B AR-mediated vasorelaxation requires activation of nitric oxide and potassium channels; however, only the A 2A ARmediated response requires protein kinase A activation. Our data are complemented by mRNA expression showing the expression of all AR subtypes with the exception of the A 3 AR. AR signaling in the PA may play an important role in mediating erection and represent a promising therapeutic option for the treatment of erectile dysfunction.

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Section: Adenosine Receptors and The Pudendal Arterysupporting

confidence: 46%

Section: Introductionmentioning

confidence: 99%

Role of Adenosine Receptor(s) in the Control of Vascular Tone in the Mouse Pudendal Artery

Labazi

Tilley

Ledent

et al. 2016

The Journal of Pharmacology and Experimental Therapeutics

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“…7,10,11 Moreover, it is validated that adenosine activates eNOS via A 2A AR in the nucleus tractus solitarii of rats, while NOS mediates A 2B AR-induced renal vasodilation in female rats. 12,13 Although the role of A 2B AR in angiogenesis has been subjected to studies, the underlying mechanism for the regulation of A 2B AR on VEGF secretion and NOS activation is poorly revealed. In the current study, we sought to evaluate whether A 2B AR is responsible for the modulation of VEGF and NOS, and then investigate the potential signaling pathways involving their regulation, which will facilitate the development of new strategies for the treatment of traumatic digit replantation and restoration of damaged tissues.…”

Section: Introductionmentioning

confidence: 99%

Adenosine A_2Breceptor stimulates angiogenesis by inducing VEGF and eNOS in human microvascular endothelial cells

Song

et al. 2015

Exp Biol Med (Maywood)

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Angiogenesis is critical to wound repair due to its role in providing oxygen and nutrients that are required to support the growth and function of reparative cells in damaged tissues. Adenosine receptors are claimed to be of paramount importance in driving wound angiogenesis by inducing VEGF. However, the underlying mechanisms for the regulation of adenosine receptors in VEGF as well as eNOS remain poorly understood. In the present study, we found that adenosine and the non-selective adenosine receptor agonists (NECA) induced tube formation in HMEC-1 in a dose-dependent manner. Adenosine or NECA (10 mmol/L) significantly augmented the number and length of the segments in comparison with the control. Simultaneously, VEGF and eNOS were significantly upregulated following the administration of 10 mmol/L NECA, while they were suppressed after A 2B AR genetic silencing and pharmacological inhibition by MRS1754. In addition, VEGF expression and eNOS bioavailability elimination significantly reduced the formation of capillary-like structures. Furthermore, the activation of A 2B AR by NECA significantly increased the intracellular cAMP levels and concomitant CREB phosphorylation, eventually leading to the production of VEGF in HMEC-1. However, the activated PKA-CREB pathway seemed to be invalidated in the induction of eNOS. Moreover, we found that the elicited PI3K/AKT signaling in response to the induction of NECA assisted in regulating eNOS but failed to impact on VEGF generation. In conclusion, the A 2B AR activation-driven angiogenesis via cAMP-PKA-CREB mediated VEGF production and PI3K/ AKT-dependent upregulation of eNOS in HMEC-1.

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“…The identity of the A 2 receptor (A 2 R) subtype (A 2A R or A 2B R) involved in the vasodilatory effect of adenosine depends on the specific vascular bed under investigation . In a recent study, we argued that the activation of adenosine A 2B R, but not A 2A R or A 3 receptors, and subsequent membrane hyperpolarization underlies the adenosine receptor‐mediated renal vasodilation in the female rat kidney …”

Section: Introductionmentioning

confidence: 99%

“…Although the interaction between nicotine and adenosinergic pathways in the modulation of biological functions, such as nociception and behaviour, has been established, no information is available to date regarding whether chronic nicotine modifies adenosinergic renovascular control. Because a recent study implicated the A 2B R/K + channel cascade in the renal vasodilatory response elicited by the adenosine analogue N ‐ethylcarboxamidoadenosine (NECA) in intact female rats, in the present study we tested the hypotheses that: (i) chronic nicotine modifies the A 2B R/K + channel‐sensitive vasodilatory action of NECA in the renal vasculature of female rats; and (ii) the hormonal status of the female rat influences the nicotine–NECA interaction in the kidney. The latter assumption receives support from the observations that nicotine, administered acutely, causes oestrogen‐dependent reductions in renal perfusion pressure (RPP) and attenuation of β‐adrenoceptor‐mediated renal vasodilation .…”

Section: Introductionmentioning

confidence: 99%

Oestrogen compromises the facilitatory effect of chronic nicotine on adenosine A_2B receptor–K⁺ channel‐mediated renal vasodilation

El‐Mas

El‐Gowilly

Elsalakawy

et al. 2014

Clin Exp Pharma Physio

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We have shown previously that the renal vasodilatory action of the adenosine analogue 5'-N-ethylcarboxamidoadenosine (NECA) in female rats is mediated via preferential activation of adenosine A2B receptor (A2B R)-K(+) channel signalling. In the present study, we tested the hypothesis that the renal vasodilatory effect of NECA and its A2B R/K(+) channel specificities are altered by chronic nicotine administration. The oestrogenic modulation of the nicotine-NECA renovascular interaction was also evaluated by determining the effect of ovariectomy (OVX) and oestrogen replacement (OVXE2) on the evoked responses. In isolated phenylephrine-preconstricted perfused kidneys obtained from sham-operated rats, vasodilation in response to cumulative bolus injections of NECA (1.6-50 nmol) or papaverine (1-243 nmol) were not affected by nicotine (1-8 mg/kg per day, i.p., 2 weeks). However, vasodilator responses to NECA, but not papaverine, were reduced in kidneys of OVX rats and restored to near-sham values after E2 replacement. Further, nicotine increased NECA-induced vasodilation in perfused kidneys from OVX rats, but failed to do so in OVXE2 preparations. The enhanced NECA responsiveness in nicotine-treated OVX preparations was abolished after infusion (into isolated kidneys) of 10 μmol/L alloxazine (A2B R antagonist) or BaCl2 plus glibenclamide (blockers of inward rectifier and ATP-sensitive K(+) channels, respectively). Vasodilator responses to 0.05-1.6 μmol minoxidil (a K(+) channel opener) were increased by nicotine in OVX, but not OVXE2, preparations and this increase was abolished after infusion of BaCl2 + glibenclamide. Together, the data suggest that chronic nicotine enhances A2B R/K(+) channel-mediated renal vasodilation in oestrogen-depleted rats.

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Nitric oxide synthase/K+ channel cascade triggers the adenosine A2B receptor-sensitive renal vasodilation in female rats

Cited by 15 publications

References 49 publications

Role of Adenosine Receptor(s) in the Control of Vascular Tone in the Mouse Pudendal Artery

Role of Adenosine Receptor(s) in the Control of Vascular Tone in the Mouse Pudendal Artery

Adenosine A_2Breceptor stimulates angiogenesis by inducing VEGF and eNOS in human microvascular endothelial cells

Oestrogen compromises the facilitatory effect of chronic nicotine on adenosine A_2B receptor–K⁺ channel‐mediated renal vasodilation

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Nitric oxide synthase/K+ channel cascade triggers the adenosine A2B receptor-sensitive renal vasodilation in female rats

Cited by 15 publications

References 49 publications

Role of Adenosine Receptor(s) in the Control of Vascular Tone in the Mouse Pudendal Artery

Role of Adenosine Receptor(s) in the Control of Vascular Tone in the Mouse Pudendal Artery

Adenosine A2Breceptor stimulates angiogenesis by inducing VEGF and eNOS in human microvascular endothelial cells

Oestrogen compromises the facilitatory effect of chronic nicotine on adenosine A2B receptor–K+ channel‐mediated renal vasodilation

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Resources

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Adenosine A_2Breceptor stimulates angiogenesis by inducing VEGF and eNOS in human microvascular endothelial cells

Oestrogen compromises the facilitatory effect of chronic nicotine on adenosine A_2B receptor–K⁺ channel‐mediated renal vasodilation