Agmatine: A novel endogenous vasodilator substance

Gao, Yuqi; Gümüşel, Bülent; Koves, Gabor; Prasad, Anand Mohan; Hao, Qingzhong; Hyman, Albert L.; Lippton, Howard

doi:10.1016/0024-3205(95)02011-7

Cited by 35 publications

(31 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, intravenous agmatine was reported to induce dose-dependent hypotension. [28][29][30] In our results, the rs16835244 SNP (A288S) in ADC was associated with a significant increase in blood pressure. We speculate that the change from alanine to serine at the 288th residue reduces the enzymatic activity of ADC, lowering the production of agmatine and increasing blood pressure.…”

Section: Discussionmentioning

confidence: 77%

Non-synonymous single-nucleotide polymorphisms associated with blood pressure and hypertension

Jin

et al. 2010

J Hum Hypertens

View full text Add to dashboard Cite

In this study, we determined the association of 1180 non-synonymous single-nucleotide polymorphisms (SNPs) with systolic blood pressure (SBP) and hypertensive status. A total of 8842 subjects were taken from two community-based cohorts-Ansung (n ¼ 4183) and Ansan (n ¼ 4659), South Korea-which had been established for genome-wide association studies (GWAS). Five SNPs (rs16835244, rs2286672, rs6265, rs17237198 and rs7312017) were significantly associated (P-values: 0.003-0.0001, not corrected for genome-wide significance) with SBP in both cohorts. Of these SNPs, rs16835244 and rs2286672 correlated with risk for hypertension. The rs16835244 SNP replaces Ala288 in arginine decarboxylase (ADC) with serine, and rs2286672 replaces Arg172 in phospholipase D2 (PLD2) with cysteine. A comparison of peptide sequences between vertebrate homologues revealed that the SNPs identified occur at conserved amino-acid residues. In silico analysis of the protein structure showed that the substitution of a polar residue, serine, for a non-polar alanine at amino-acid residue 288 affects a conformational change in ADC, and that Arg172 in PLD2 resides in the PX domain, which is important for membrane trafficking. These results provide insights into the function of these non-synonymous SNPs in the development of hypertension. The study investigating non-synonymous SNPs from GWAS not only by statistical association analysis but also by biological relevance through the protein structure might be a good approach for identifying genetic risk factors for hypertension, in addition to discovering causative variations.

show abstract

Section: Discussionmentioning

confidence: 77%

Non-synonymous single-nucleotide polymorphisms associated with blood pressure and hypertension

Jin

et al. 2010

J Hum Hypertens

View full text Add to dashboard Cite

show abstract

“…Agmatine is known to be an agonist of imidazoline receptors (Gao et al . ; Wu et al . ), which are classified into at least 3 subtypes – I 1 ‐, I 2 ‐ and I 3 ‐imidazoline receptors (Morgan & Chan ; Kaliszan et al .…”

Section: Discussionmentioning

confidence: 99%

Changes of imidazoline receptors in spontaneously hypertensive rats

Mar

Chou

Chung

et al. 2012

Int J Experimental Path

View full text Add to dashboard Cite

The role of imidazoline receptors in the regulation of vascular function remains unclear. In this study, we evaluated the effect of agmatine, an imidazoline receptor agonist, on systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) and investigated the expressions of imidazoline receptors by Western blot. The isometric tension of aortic rings isolated from male SHRs was also estimated. Agmatine decreased SBP in a dose-dependent manner in SHRs but not in the normal group [Wistar-Kyoto (WKY) rats]. This reduction in SBP in SHRs was abolished by BU224, a selective antagonist of imidazoline I(2) -receptors. Higher expression of imidazoline receptors in SHR was observed. Moreover, agmatine-induced relaxation in isolated aortic rings precontracted with phenylephrine or KCl. This relaxation was also abolished by BU224 but was not modified by efaroxan, an imidazoline I(1) -receptor antagonist. Agmatine-induced relaxation was also attenuated by PNU 37883, a selective blocker of vascular ATP-sensitive potassium (K(ATP) ) channels. Additionally, vasodilatation by agmatine was reduced by an inhibitor of protein kinase A (PKA). We suggest that agmatine can lower blood pressure in SHRs through activation of the peripheral imidazoline I(2) -receptor, which is expressed more highly in SHRs.

show abstract

“…For instance, we and others documented that dietary supplementation with L-arginine reduces the aggravation of hypertension and the progression of renal failure in rats with reduced renal mass that are associated with an increase in NO availability and a reduction in ET-1 production [10]. However, it has been postulated that the protective effect of L-arginine could be due, in part, to an increase in agmatine generation, an endogenous non-catecholamine ligand for alpha-2 adrenoceptors and imidazoline receptors produced by arginine decarboxylase that has cardiovascular beneficial proprieties [11]. Similar to L-arginine supplementation, vascular and renal protection has been reported with tetrahydrobiopterin (BH 4 ) supplementation, a critical cofactor for eNOS activity [12].…”

Section: Introductionmentioning

confidence: 99%

eNOS gene delivery prevents hypertension and reduces renal failure and injury in rats with reduced renal mass

Savard

Lavoie

Villeneuve

et al. 2011

Nephrology Dialysis Transplantation

View full text Add to dashboard Cite

Background. Impaired nitric oxide (NO) release in chronic renal failure has been implicated in the pathogenesis of hypertension and the progression of renal insufficiency. We investigated whether gene delivery of the endothelial NO synthase (eNOS) improves NO release and reduces blood pressure and renal failure and injury in rats with reduced renal mass. Methods. Renal failure was induced by renal artery branches ligation. Two weeks later, rats with renal failure were divided into three groups and received an intravenous injection of the vehicle or the adenovirus that expresses eNOS or b-galactosidase (b-gal). Systolic blood pressure, renal parameters and histopathology were assessed at Week 4 after gene delivery. Results. At the end of the study, systolic blood pressures, serum creatinine, proteinuria, urinary endothelin-1 (ET-1) excretion and renal cortex ET-1 levels were increased, whereas plasma and urine NO 2 /NO 3 were reduced in renal failure rats as compared to normal controls. Renal injury comprised blood vessel media hypertrophy, focal and segmental glomerular sclerosis, tubular atrophy and interstitial fibrosis. Gene delivery of eNOS, but not b-gal, prevented an increase in systolic blood pressure and proteinuria, and a reduction in plasma and urine NO 2 /NO 3 . eNOS gene delivery also reduced a rise in serum creatinine, urinary ET-1 excretion and renal cortex ET-1 levels, and the renal vascular, glomerular and tubular injury. Conclusion. This study indicates that eNOS gene delivery in rats with renal failure improves NO release, which likely prevents the aggravation of hypertension and slows down the progression of renal failure and injury.

show abstract

Agmatine: A novel endogenous vasodilator substance

Cited by 35 publications

References 2 publications

Non-synonymous single-nucleotide polymorphisms associated with blood pressure and hypertension

Non-synonymous single-nucleotide polymorphisms associated with blood pressure and hypertension

Changes of imidazoline receptors in spontaneously hypertensive rats

eNOS gene delivery prevents hypertension and reduces renal failure and injury in rats with reduced renal mass

Contact Info

Product

Resources

About