Humoral effects of selective adenosine agonists in spontaneously hypertensive rats

Sala, Carla; Monopoli, Angela; Alberti, Cristina; Casati, Carlo; Ongini, Ennio; Zanchetti, Alberto; Morganti, Alberto

doi:10.1097/00004872-199601000-00010

Cited by 7 publications

(6 citation statements)

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“…Therefore, our results rule out any role for Ado, A 2a AdoR and SR-141617A in the regulation of ET-1 production by HUVEC. This finding agrees with previous results at the physiological level indicating no effect of A 2a agonists on ET-1 production in spontaneously hypertensive rats [23] .…”

Section: Discussionsupporting

confidence: 94%

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Anandamide Inhibits Endothelin-1 Production by Human Cultured Endothelial Cells: A New Vascular Action of This Endocannabinoid

et al. 2006

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The endogenous cannabinoid receptor agonist anandamide (AEA) exerts vascular effects such as vasodilatation and hypotension. In this study, we determined the effect of AEA on endothelin-1 production by cultured human umbilical vein endothelial cells. Anandamide (≧5 µmol/l) significantly decreased endothelin-1 production in a dose-dependent manner, a response not affected by the specific CB₁ receptor antagonist/inverse agonist SR-141716A. Adenosine, via activation of adenosine receptors (also targets for SR-141716A), was not involved in these effects. Conversely, AEA increased nitric oxide (NO) production, an effect inhibited by SR-141716A, indicating the involvement of CB₁ receptors. Therefore, we hypothesize that AEA effects on endothelial cells may lead to vasodilatation through independent concerted mechanisms, involving a non-CB₁ receptor-dependent inhibition of endothelin-1 production and a CB₁-mediated increase of NO.

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Section: Discussionsupporting

confidence: 94%

“…The effects of AEA on vasodilatation have endothelium-dependent and endothelium-independent components [23,24] . The presence of CB 1 mRNA and protein in rat and human vascular endothelial cells indicates the involvement of CB 1 , SR-141716A-sensitive receptors in AEA-induced vasodilatation [7] .…”

Section: Discussionmentioning

confidence: 99%

Anandamide Inhibits Endothelin-1 Production by Human Cultured Endothelial Cells: A New Vascular Action of This Endocannabinoid

et al. 2006

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“…We found that adenosine increases the ANP release directly from beating atria with negative inotropism. Our results agree with other reports that adenosine increases plasma concentration of ANP in vivo 9,10 and in vitro experiments. 11 Elias et al 9 found a marked increase in plasma ANP and antidiuretic hormone levels despite a marked reduction in arterial blood pressure.…”

Section: Discussionsupporting

confidence: 93%

“…Studies have indicated that adenosine increases plasma concentration of atrial natriuretic peptide (ANP) 9,10 and ventricular ANP gene expression. 11 However, the molecular mechanisms of adenosine-mediated ANP secretion has not been fully addressed 9,12 and is still controversial.…”

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confidence: 99%

Adenosine-Stimulated Atrial Natriuretic Peptide Release Through A ₁ Receptor Subtype

et al. 2005

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Abstract-Adenosine acts as an important protector of ischemic myocardium through coronary vasodilation and the depression of cardiac contractility. The protective effect of adenosine may partly relate to the cardiac hormone atrial natriuretic peptide (ANP). The aim of the present study was to investigate the effects of adenosine and the adenosine receptor subtype on atrial hemodynamics and ANP release using isolated perfused beating rat atria. Adenosine, a nonselective adenosine receptor agonist, increased the ANP release with negative inotropism in a dose-dependent manner. Adenosine-stimulated ANP release was attenuated by a selective A 1 antagonist but not A 2A antagonist or A 3 antagonist. The order of potency of the various agonists for the ANP release was A 1 agonistsϾ ϾA 3 agonistϭ adenosineϾA 2A agonist. The order of potency for the negative inotropy was A 1 agonistsϾadenosineϭA 2A agonistϾA 3 agonist. The negative inotropism and ANP release by a specific A 1 agonist (N 6 -cyclopentyl-adenosine) were also attenuated by A 1 antagonist but not A 2A antagonist or A 3 antagonist. Treatment with A 1 agonist resulted in a decrease of cAMP contents in atria and perfusates. The agonist-stimulated ANP release was significantly attenuated in the presence of forskolin, isoproterenol 8-Br-cAMP, or an adenylyl cyclase inhibitor. These results suggest that the A 1 receptor subtype is responsible for the adenosine-induced ANP release and negative inotropism through adenylyl cyclase-cAMP pathway. Key Words: adenosine Ⅲ natriuretic peptides Ⅲ cyclin AMP Ⅲ heart Ⅲ hypertension, experimental Ⅲ receptor Ⅲ kidney A denosine is recognized as an important signaling molecule in heart. Adenosine originates from the hydrolysis of S-adenosylhomocysteine (SAH) by SAH hydrolase during normal condition or from the hydrolysis of AMP by 5Ј-nucleotidase during ischemic or hypoxic conditions. 1 Adenosine effects are mediated through 4 distinct receptors, A 1 , A 2A , A 2B , and A 3 , initially defined pharmacologically based on their effects on adenylyl cyclase (AC; inhibition or stimulation) and their selectivity for agonists and antagonists. [2][3][4] All the receptor subtypes appear to be expressed in cardiomyocytes. 4 In the cardiovascular system, adenosine causes coronary vasodilation, the reduction of heart rate and cardiac contractility, and the attenuation of stimulatory actions of catecholamines on heart. 5 Endogenous release of adenosine during myocardial ischemia and hypoxia induces a potent protective effect in paracrine and autocrine ways. 6 Adenosine produced during a brief period of ischemia or exogenously administered adenosine causes a cardioprotective effect manifested by a reduction of infarct size or decreased myocardial stunning during ischemic preconditioning 7 via activation of A 1 and A 3 receptor subtypes. 5,8 Myocardial adenosine and ADP levels are increased during hypoxia and in severely hypertrophied hearts. Therefore, adenosine can exert effects on the ischemic or overloaded heart that are of considerable scie...

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“…Mean blood pressure was measured weekly by the tail/cuff method. 15 All procedures were performed in accordance with the guidelines of the China Council on Animal Care. Apomorphine (APO) was purchased from Sigma Inc.…”

Section: Methodsmentioning

confidence: 99%

Ultrastructural comparison of penile cavernous tissue between hypertensive and normotensive rats

et al. 2005

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Our aim was to compare the ultrastructure of penile cavernous tissue in the spontaneous hypertensive rat (SHR) and normotensive rat, and study the relation of blood pressure with erectile function. After injection of apomorphine (APO), penile erectile frequency in 16-week-old SHR (group A) and Wistar-Kyoto rat (WKY) (group B) was observed and noted. The ultrastructure of the penile cavernous tissue was studied by scanning electron microscope and transmission electron microscope. The mean blood pressures were significantly higher in group A than in group B (P ¼ 0; 171.20710.94 and 117.60712.38, n ¼ 5, for group A and group B, respectively). After treatment of the two groups with APO, the erectile frequency in group A was significantly less than in group B (P ¼ 0.007; 0.4070.55 and 2.4071.14, n ¼ 5, for group A and group B, respectively). Significant ultrastructural pathological changes were observed in the tunica albuginea and penile cavernous tissue of SHR. The elastic fibers were decreased and the collagen fibers of the sinusoid were increased in group A. The tunica albuginea thickness (mean7s.d.) was 100.2077.22 lm and 126.0077.65 lm in group A and group B, respectively. The tunica albuginea of group A was significantly thinner than that in B (P ¼ 0.001). Some endothelial cells and smooth muscle cells exhibited damaged mitochondria, and endoplasmic reticulums and Schwann cells were degenerated in group A. Although the function of penile erection might be affected by a secondary effect related to endothelial dysfunction of hypertension, these ultrastructural pathological changes of the penile cavernous tissue might also be one of the important mechanisms of erectile dysfunction caused by hypertension.

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Humoral effects of selective adenosine agonists in spontaneously hypertensive rats

Cited by 7 publications

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Anandamide Inhibits Endothelin-1 Production by Human Cultured Endothelial Cells: A New Vascular Action of This Endocannabinoid

Anandamide Inhibits Endothelin-1 Production by Human Cultured Endothelial Cells: A New Vascular Action of This Endocannabinoid

Adenosine-Stimulated Atrial Natriuretic Peptide Release Through A ₁ Receptor Subtype

Ultrastructural comparison of penile cavernous tissue between hypertensive and normotensive rats

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Humoral effects of selective adenosine agonists in spontaneously hypertensive rats

Cited by 7 publications

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Anandamide Inhibits Endothelin-1 Production by Human Cultured Endothelial Cells: A New Vascular Action of This Endocannabinoid

Anandamide Inhibits Endothelin-1 Production by Human Cultured Endothelial Cells: A New Vascular Action of This Endocannabinoid

Adenosine-Stimulated Atrial Natriuretic Peptide Release Through A 1 Receptor Subtype

Ultrastructural comparison of penile cavernous tissue between hypertensive and normotensive rats

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Adenosine-Stimulated Atrial Natriuretic Peptide Release Through A ₁ Receptor Subtype