Effect of adrnomedullin on renal hemodynamics and functions in dogs

doi:10.1016/0014-2999(94)90524-X

European Journal of Pharmacology

Volume 263, Issues 1–2, 22 September 1994, Pages 69-73

https://doi.org/10.1016/0014-2999(94)90524-X Get rights and content

Abstract

In order to elucidate the role of adrenomedullin the kidney, we investigated the effects of adrenomedullin on renal hemodynamics and urine formation in anesthetized dogs. Intrarenal arterial infusion of adrenomedullin (0.8, 4 and 20 ng · kg⁻¹ · min⁻¹ elicited dose-dependent increases in renal blood flow (by 10, 26 and 37%, respectively) with no change in blood pressure or heart rate, indicating a renal vasodilatory action of adrenomedullin. The glomerular filtration rate did not increase with the lower two doses, but increased marginally by 9% at the highest dose. Infusion of adrenomedullin at the rates of 4 and 20 ng · kg⁻¹ · min⁻¹ inreased urine flow and the urinary excretion of sodium and potassium dose dependently. Arterial and renal venous plasma renin activity was unaffected by adrenomedullin. The findings indicate that adrenomedullin is a potent renal vasodilatory peptide with a diuretic action. Since the threshold for the renal vasodilatory action of adrenomedullin is close to its physiological concentration in human plasma, adrenomedullin may play an important role in the regulation of renal function.

References (13)

Y. Ishiyama et al.
Hemodynamic effects of a novel hypotensive peptide, human adrenomedullin, in rats
Eur. J. Pharmacol.
(1993)
K. Kitamura et al.
Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma
Biochem. Biophys. Res. Commun.
(1993)
K. Kitamura et al.
Cloning and characterization of cDNA encoding a precursor for human adrenomedullin
Biochem. Biophys. Res. Commun.
(1993)
J. Sakata et al.
Molecular cloning and biological activities of rat adrenomedullin, a hypotensive peptide
Biochem. Biophys. Res. Commun.
(1993)
J. Ueda et al.
Effect of glucagon on renin secretion in the dog
Eur. J. Pharmacol.
(1978)
D.R. Bruna et al.
Renin mRNA quantification using polymerase chain reaction in cultured juxtaglomerular cells. Short-term effects of cAMP on renin mRNA and secretion
Cir. Res.
(1993)

There are more references available in the full text version of this article.

Cited by (198)

Different subpopulations of kidney interstitial cells produce erythropoietin and factors supporting tissue oxygenation in response to hypoxia in vivo
2020, Kidney International
Citation Excerpt :
These results are in good accordance with other studies showing the hypoxia inducibility of ADM and RGS4.35–39 ADM has been described to increase renal perfusion as well as salt and water excretion.40,41 Therefore, it is conceivable that hypoxemic induction of ADM production in the interstitium leads to an increase in interstitial perfusion and to a lowering of energy consuming sodium resorption.
Genetic induction of hypoxia signaling by deletion of the von Hippel-Lindau (Vhl) protein in mesenchymal PDGFR-β⁺ cells leads to abundant HIF-2 dependent erythropoietin (EPO) expression in the cortex and outer medulla of the kidney. This rather unique feature of kidney PDGFR-β⁺ cells promote questions about their special characteristics and general functional response to hypoxia. To address these issues, we characterized kidney PDGFR-β⁺ EPO expressing cells based on additional cell markers and their gene expression profile in response to hypoxia signaling induced by targeted deletion of Vhl or exposure to low oxygen and carbon monoxide respectively, and after unilateral ureteral obstruction. CD73⁺, Gli1⁺, tenascin C⁺ and interstitial SMMHC⁺ cells were identified as zonally distributed subpopulations of PDGFR-β⁺ cells. EPO expression could be induced by Vhl deletion in all PDGFR-β⁺ subpopulations. Under hypoxemic conditions, recruited EPO⁺ cells were mostly part of the CD73⁺ subpopulation. Besides EPO production, expression of adrenomedullin and regulator of G-protein signaling 4 was upregulated in PDGFR-β⁺ subpopulations in response to the different hypoxic stimuli. Thus, different kidney interstitial PDGFR-β⁺ subpopulations exist, capable of producing EPO in response to different stimuli. Activation of hypoxia signaling in these cells also induces factors likely contributing to improved kidney interstitial tissue oxygenation.
The potential of novel peptides in the management of children with Congenital Heart Disease: Above and beyond the BNP
2017, Progress in Pediatric Cardiology
Citation Excerpt :
Moreover, ADM is produced in the heart, lung, aorta, vessels (vascular smooth muscle cells and endothelial cells) [33]. Other effects of ADM in cardiovascular system include a diuretic action as reported in a study in dogs [38], urinary sodium excretion [39] and inhibition of aldosterone production in the rats [40]. In addition to the above effects, studies have shown that ADM has a beneficial effect in cardiac output, which results from the reduction of blood pressure and the attenuation of the reflex-mediated sympathetic activation [41].
Congenital Heart Disease (CHD) constitutes a common cause of major congenital abnormalities with prevalence around 8.2 per 1000 live births in Europe. Despite the important advances in the diagnosis, treatment and management of CHD patients throughout the years, it remains a challenge how to better manage the children with CHD using the biomarkers. However, in the last decade, B-type Natriuretic Peptide (BNP) and less often Adrenomedullin (ADM) and Urotensin II (UT II) have become the focus of research, in view of the improvement in the management of patients with CHD. Moreover, despite crescent evidences supporting the use of BNP as diagnostic and prognostic marker in children with CHD, its use remains limited and guidelines/expert consensus recommendations are lacking. Adrenomedullin (ADM) and Urotensin II (UT II) are two potent vasoactive peptides that might play a role in the development of pulmonary hypertension. Future studies are needed to explore the role of both peptides as biomarkers of pulmonary hypertension and their prognostic significance on the development of pulmonary hypertension in CHD patients.
Adrenomedullin As A Renal Peptide
2006, Handbook of Biologically Active Peptides
Although blood vessels are considered the major source of plasma adrenomedullin (AM), the kidney produces and secretes AM and the kidney is also a target organ for AM. AM has renal vasorelaxing actions and increases regional blood flow to the renal medulla and cortex. AM promotes natriuresis and diuresis, which are mediated through an increase in glomerular filtration rate and a decrease in distal tubular sodium reabsorption. Renal AM is modulated in various renal diseases, such as chronic renal failure, glomerulonephritis, IgA nephropathy, and urinary tract infection. Gene delivery of AM and chronic administration of AM have renoprotective actions in cardiorenal disorders. AM is a renal peptide that plays an important autocrine and/or paracrine role in the regulation of renal function.
Novel Biomarkers of Renal Dysfunction and Congestion in Heart Failure
2022, Journal of Personalized Medicine
Early Biomarkers of Altered Renal Function and Orthostatic Intolerance During 10-day Bedrest
2022, Frontiers in Physiology
Pharmacological HIF-PHD inhibition reduces renovascular resistance and increases glomerular filtration by stimulating nitric oxide generation
2021, Acta Physiologica

View all citing articles on Scopus

View full text

Effect of adrnomedullin on renal hemodynamics and functions in dogs

Abstract

Eur. J. Pharmacol.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Eur. J. Pharmacol.

Renin mRNA quantification using polymerase chain reaction in cultured juxtaglomerular cells. Short-term effects of cAMP on renin mRNA and secretion

Cir. Res.