Hypertension induced by nitric oxide synthase inhibitor increases responsiveness of ventricular myocardium and aorta of rat tissue to adrenomedullin stimulation in vitro

Pan, Chun; Zhong, Guang Zhen; Zhao, Jing; Pang, Yiming; Tang, Chao; Qi, Yong

doi:10.1016/j.lfs.2005.04.082

Cited by 12 publications

(5 citation statements)

References 33 publications

(25 reference statements)

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“…This conclusion is in agreement with the observation of Pan and coworkers [57] who reported that AM stimulated cAMP accumulation in myocardial tissue sections in vitro and that accumulation of this second messenger substance was augmented in tissue from rats subjected to chronic NO deficiency, consistent with an up-regulation in receptor number, which they [57] and we have [13] observed in myocardial tissue and cardiomyocytes, respectively. Further studies are warranted to address receptor-subtype involvement and coupling to signal transduction pathways in protection against cardiomyocyte oxidative stress and hypertrophy.…”

Section: Discussionsupporting

confidence: 93%

Adrenomedullin Gene Delivery is Cardio-protective in a Model of Chronic Nitric Oxide Deficiency Combining Pressure Overload, Oxidative Stress and Cardiomyocyte Hypertrophy

Bell

Campbell

Wang

et al. 2010

Cell Physiol Biochem

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Background/aims: Chronic inhibition of nitric oxide (NO) synthesis is associated with hypertension, myocardial ischemia, oxidative stress and hypertrophy; expression of the vasodilator peptide, adrenomedullin (AM) and its receptors is augmented in cardiomyocytes, indicating that the myocardial AM system may be activated in response to pressure loading and ischemic insult to serve a counter-regulatory, cardio-protective role. The study examined the hypothesis that oxidative stress and hypertrophic remodeling in NO-deficient cardiomyocytes are attenuated by adenoviral vector-mediated delivery of the human adrenomedullin (hAM) gene in vivo. Methods: The NO synthesis inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME, 15mg · kg^-1 · day^-1) was given to rats for 4 weeks following systemic administration via the tail vein of a single injection of either adenovirus harbouring hAM cDNA under the control of the cytomegalovirus promoter-enhancer (Ad.CMV-hAM-4F2), or for comparison, adenovirus alone (Ad.Null) or saline. Cardiomyocytes were subsequently isolated for assessment of the influence of each intervention on parameters of oxidative stress and hypertrophic remodelling. Results: Cardiomyocyte expression of the transgene persisted for ≧4 weeks following systemic administration of adenoviral vector. In L-NAME treated rats, relative to Ad.Null or saline administration, Ad.CMV-hAM-4F2 (i) reduced augmented cardiomyocyte membrane protein oxidation and mRNA expression of pro-oxidant (p22phox) and anti-oxidant (SOD-3, GPx) genes; (ii) attenuated increased cardiomyocyte width and mRNA expression of hypertrophic (sk-α-actin) and cardio-endocrine (ANP) genes; (iii) did not attenuate hypertension. Conclusions: Adenoviral vector mediated delivery of hAM resulted in attenuation of myocardial oxidative stress and hypertrophic remodelling in the absence of blood pressure reduction in this model of chronic NO-deficiency. These findings are consistent with a direct cardio-protective action in the myocardium of locally-derived hAM which is not dependant on NO generation.

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Section: Discussionsupporting

confidence: 93%

Adrenomedullin Gene Delivery is Cardio-protective in a Model of Chronic Nitric Oxide Deficiency Combining Pressure Overload, Oxidative Stress and Cardiomyocyte Hypertrophy

Bell

Campbell

Wang

et al. 2010

Cell Physiol Biochem

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“…This has subsequently been demonstrated in animal models, in which abundant AM and NO lead to severe acute multiple organ failure (heart, lung, liver and kidney) (25). The link between these two molecules has also been demonstrated clinically in cardiomyopathy and hypertension (27,28), pre-eclampsia (29), intrauterine growth restriction (30), diabetic retinopathy (31), depressive disorders and schizophrenia (32,33). Owing to its regulatory role, AM has been suggested as a marker of disease, for example, in decreased ovarian function (34,35), and as a target for treatment of cancer (36), depression (37) and arrhythmia (38).…”

mentioning

confidence: 94%

Detection of adrenomedullin and nitric oxide in different forms of periodontal disease

Hussain

McKay

Gonzales-Marin

et al. 2015

J of Periodontal Research

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“…This sizeable temporal delay strongly suggests that up-regulation of RAMP2 and RAMP3, and consequently of AM1-R and AM2-R, depends on the increased local production of AM. According to this view, findings are available showing that under various pathological and experimental conditions a strict positive correlation exists between AM and RAMP2/3 expression in cardiomyocytes (24)(25)(26)(27). Moreover, recent evidence showed that AM (10 -8 M) enhanced AM1-R expression in cultured immortalized human microvascular endothelial cells (28).…”

Section: Discussionmentioning

confidence: 97%

Up-regulation of adrenomedullin receptor gene expression in activated local stem cells during rat adrenal regeneration

Rebuffat

Macchi²,

Malendowicz³

et al. 2007

Int J Mol Med

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Abstract. Previous studies showed that adrenomedullin (AM) gene expression was up-regulated in the regenerating rat adrenal cortex after enucleation and contra-lateral adrenalectomy, the effect being significant at day 1 after surgery and peaking between days 3 and 7. Using the same experimental model, we investigated by real time-polymerase chain reaction the mRNA expression of the AM receptor components: calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMP)2 and 3. At time 0 (60 min after enucleation; control group), the CRLR mRNA content was ~2-and 5-fold higher than that of RAMP2 and RAMP3, respectively. No significant changes in CRLR mRNA expression were observed in relation to the time elapsed from enucleation. RAMP2 and RAMP3 mRNAs did not exhibit significant changes at day 1 after surgery, but underwent a marked increase between days 3 and 7. The mRNA content of the two RAMPs decreased at days 14 and 28, although remaining significantly higher than that of the controls. These findings indicate that the AM receptor subtypes AM1-R (CRLR-RAMP2) and AM2-R (CRLR-RAMP3) are up-regulated in enucleated adrenals, and the hypothesis is advanced that this effect depends on the increased local production of AM. The concerted increase in AM and its receptor expression would greatly improve the autocrine-paracrine mechanism(s) by which AM favors proliferation of zona glomerulosa stem cells during adrenal regeneration.

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Hypertension induced by nitric oxide synthase inhibitor increases responsiveness of ventricular myocardium and aorta of rat tissue to adrenomedullin stimulation in vitro

Cited by 12 publications

References 33 publications

Adrenomedullin Gene Delivery is Cardio-protective in a Model of Chronic Nitric Oxide Deficiency Combining Pressure Overload, Oxidative Stress and Cardiomyocyte Hypertrophy

Adrenomedullin Gene Delivery is Cardio-protective in a Model of Chronic Nitric Oxide Deficiency Combining Pressure Overload, Oxidative Stress and Cardiomyocyte Hypertrophy

Detection of adrenomedullin and nitric oxide in different forms of periodontal disease

Up-regulation of adrenomedullin receptor gene expression in activated local stem cells during rat adrenal regeneration

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