Synthetic human adrenomedullin and ADM15-52 have potent short-lasting vasodilator activity in the pulmonary vascular bed of the cat

Cheng, David Y.; DeWitt, Bracken J.; Wegmann, Michael J.; Coy, David H.; Bitar, Kamal G.; Murphy, William A.; Kadowitz, Philip J.

doi:10.1016/0024-3205(94)00246-0

Cited by 29 publications

(22 citation statements)

References 8 publications

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“…Bolus injection or infusion of AM in humans (5-10) and in several animal species (11)(12)(13)(14)(15)(16)(17) causes prolonged, dosedependent vasorelaxation and hypotension. Yet the dose, route, and duration of exogenous administration required to elicit a systemic effect on blood pressure (BP) varies widely among published studies (8)(9)(10).…”

mentioning

confidence: 99%

Adrenomedullin gene expression differences in mice do not affect blood pressure but modulate hypertension-induced pathology in males

Caron¹,

Hagaman

Nishikimi

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Adrenomedullin (AM) is a potent vasodilator peptide in plasma at picomolar levels. Polymorphisms in the human AM gene have been associated with genetic predisposition to diabetic nephropathy and proteinuria with essential hypertension, and numerous studies have demonstrated that endogenous AM plays a role in protecting the heart and kidneys from fibrosis resulting from cardiovascular disease. Elevated plasma levels of AM are associated with pregnancy and sepsis and with cardiovascular stress and hypertension. However, there are no reports of the effects of genetic differences in the expression of the endogenous AM gene and of gender on blood pressure in these circumstances or on the pathological changes accompanying hypertension. To address these questions, we have generated mice having genetically controlled levels of AM mRNA ranging from Ϸ50% to Ϸ140% of wild-type levels. These modest changes in AM gene expression have no effect on basal blood pressure. Although pregnancy and sepsis increase plasma AM levels, genetically reducing AM production does not affect the transient hypotension that occurs during normal pregnancy or that is induced by treatment with lipopolysaccharide. Nor does the reduction of AM affect chronic hypertension caused by a renin transgene. However, 50% normal expression of AM enhances cardiac hypertrophy and renal damage in male, but not female, mice with a renin transgene. These observations suggest that the effect of gender on the role of AM in counteracting cardiovascular damage in humans merits careful evaluation. cardiovascular ͉ pregnancy ͉ cardiac hypertrophy ͉ renal fibrosis ͉ gene targeting A drenomedullin (AM) is a 52-aa peptide vasodilator which circulates in the plasma as a protein-bound hormone and can influence many biological processes (1). The gene coding for AM is widely expressed throughout the body, most highly in endothelial cells and vascular smooth muscle cells (2, 3). Consequently, highly vascularized tissues, such as the placenta, lung, heart, and kidney cause elevated plasma AM levels when their secretion of AM peptide is stimulated by conditions such as pregnancy, sepsis, and cardiovascular disease or by inflammatory cytokines or hypoxia.AM is most widely known for its vasodilatory properties (4). Bolus injection or infusion of AM in humans (5-10) and in several animal species (11-17) causes prolonged, dosedependent vasorelaxation and hypotension. Yet the dose, route, and duration of exogenous administration required to elicit a systemic effect on blood pressure (BP) varies widely among published studies (8-10). Moreover, it is possible that bolus infusions of the unbound peptide may not accurately replicate the functions of the endogenous protein-bound peptide. Consequently, it is important to determine whether modest changes in expression of the endogenous AM gene affect the maintenance of BP during health and disease.Endogenous AM plays a role in protecting the heart and kidneys from damage during cardiovascular stresses such as hypertension and its associated ...

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mentioning

confidence: 99%

Adrenomedullin gene expression differences in mice do not affect blood pressure but modulate hypertension-induced pathology in males

Caron¹,

Hagaman

Nishikimi

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…In adult animals, several studies have demonstrated that AM produces vasodilatation in pulmonary circulation (Cheng et al, 1994;Heaton et al, 1995;Lippton et al, 1994). Very interestingly, AM was demonstrated to significantly increase pulmonary blood flow in late gestation fetal lambs, reaching levels equal to those normally achieved postnatally (de Vroomen et al, 1997).…”

Section: Am and Perinatal Adaptationmentioning

confidence: 95%

Adrenomedullin in mammalian embryogenesis

Garayoa

Bodegas

Cuttitta

et al. 2002

Microscopy Res & Technique

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Here are summarized data supporting that adrenomedullin (AM) is a multifunctional factor involved in the complex regulatory mechanisms of mammalian development. During rodent embryogenesis, AM is first expressed in the heart, followed by a broader but also defined spatio-temporal pattern of expression in vascular, neural, and skeletal-forming tissues as well as in the main embryonic internal organs. AM pattern of expression is suggestive of its involvement in the control of embryonic invasion, proliferation, and differentiation processes, probably through autocrine or paracrine modes of action. AM levels in fetoplacental tissues, uterus, maternal and umbilical plasma are highly increased during normal gestation. These findings in addition to other physiological and gene targeting studies support the importance of AM as a vasorelaxant factor implicated in the regulation of maternal vascular adaptation to pregnancy, as well as of fetal and fetoplacental circulations. AM is also present in amniotic fluid and milk, which is suggestive of additional functions in the maturation and immunological protection of the fetus. Altered expression of AM has been found in some gestational pathologies, although it is not yet clear whether this corresponds to causative or compensatory mechanisms. Future studies in regard to the distribution and expression levels of the molecules known to function as AM receptors, together with data on the action of complement factor H (an AM binding protein), may help to better define the roles of AM during embryonic development.

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“…We used three anti-AM monoclonal antibodies (23,24): one recognized the ring structure (rAdR-2; anti-rat AM [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]), one the C-terminal amide structure (AdC-1; anti-AM[46-52]NH2), and one the middle portion (AdM-2; anti-AM [25][26][27][28][29][30][31][32][33][34][35][36]) of the molecule. These antibodies were gifted from Shionogi & Co., Ltd., Osaka, Japan.…”

Section: Preparation Of Antibodiesmentioning

confidence: 99%

“…Monoclonal mouse anti-AM [12][13][14][15][16][17][18][19][20][21][22][23][24][25]Fab was conjugated with 6-maleimidohexanoyl-2,4 DNP-biotinyl-BSA and used as a capture antibody (26,27 (26,27).…”

Section: Preparation Of Capture Antibody and Antibody-labeled Enzymementioning

confidence: 99%

“…To measure rat AM-m, an aliquot (10 µl) of standard AM-m, plasma sample or tissue extract was mixed with 140 µl of AM buffer containing 0.1% Triton X-100, 50 KIU/ml of aprotinin, 10 fmol of 2,4-DNP-biotinyl-BSA-anti-AM [12][13][14][15][16][17][18][19][20][21][22][23][24][25] Fab conjugate (as a capture antibody) and 3 fmol of anti-AM[46-52]NH2 Fab -β-D-galactosidase conjugate (as an antibody-enzyme) and incubated overnight at 4 ºC without shaking (first incubation; Formation). Thereafter, the mixture was incubated with one streptavidin-coated polystyrene bead for 30 min at room temperature with shaking (210 strokes/min, second incubation; Entrapment).…”

Section: Two-site Immunoenzymometric Assay (Iema) For Rat Am-m and Am-tmentioning

confidence: 99%

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Direct Measurement of Glycine-Extended Adrenomedullin in Plasma and Tissue Using an Ultrasensitive Immune Complex Transfer Enzyme Immunoassay in Rats

et al. 2003

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Synthetic human adrenomedullin and ADM15-52 have potent short-lasting vasodilator activity in the pulmonary vascular bed of the cat

Cited by 29 publications

References 8 publications

Adrenomedullin gene expression differences in mice do not affect blood pressure but modulate hypertension-induced pathology in males

Adrenomedullin gene expression differences in mice do not affect blood pressure but modulate hypertension-induced pathology in males

Adrenomedullin in mammalian embryogenesis

Direct Measurement of Glycine-Extended Adrenomedullin in Plasma and Tissue Using an Ultrasensitive Immune Complex Transfer Enzyme Immunoassay in Rats

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