Role of Endothelin-1/Endothelin Receptor System in Endotoxic Shock Rats.

Ishimaru, Shinya; Shichiri, Masayoshi; Mineshita, Satoru; Hirata, Yukio

doi:10.1291/hypres.24.119

Cited by 30 publications

(27 citation statements)

References 36 publications

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“…Taken together, our previous and current results suggest a role of Gα13 in ETBR-mediated ET-1 autoinduction and other ET-1-mediated pathophysiological reactions. It is well known that endothelin production is up-regulated by various stimuli such as TGF-β, tumor necrosis factor (TNF)-α, interleukins, insulin, norepinephrin, angiotensin II (via AT1 receptors), thrombin, and other physicochemical factors (22,23,27). Since Gα13 interacts with AT1 receptors and thrombin receptors (3,5), Gα13 could play an important role in induction of endothelin by these peptides.…”

Section: Discussionmentioning

confidence: 99%

“…Gα13 regulates Na/H exchanger activity (7,8), extracellular signal regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) (9 -11), nuclear factor κB (NF-κB) (12) and the activity of the low molecular weight GTPase, Rho (13 -15), and is also capable of neoplastic transformation, induction of apoptosis, and stimulation of actin reprotein kinases (ERK, JNK, and p38) (23,24). Because of its vasoconstrictor and growth-promoting action, numerous studies indicate that ET-1 is involved in the pathogenesis of a broad spectrum of renal and cardiovascular diseases (21,22,(25)(26)(27). Previous studies have demonstrated that ET-1 induced ET-1 production through ETAR and/or ETBR-mediated pathways, suggesting that a sustained ET-1 autocrine loop contributes to the progression of cardiovascular and renal diseases (28)(29)(30)(31)(32).…”

Section: Introductionmentioning

confidence: 99%

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G.ALPHA.13 Induces PreproET-1 Gene Expression via JNK.

et al. 2002

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The endothelin B receptor (ETBR) has been shown to mediate autoinduction of endothelin-1 (ET-1). We previously reported that the ETBR interacts with G 13, a member of the heterotrimeric GTP-binding protein family.In the present study, we examined whether G 13 induces preproET-1 (ppET-1) gene transcription, which could result in ET-1 autoinduction in a renal epithelial cell line. We generated a reporter gene construct un-

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

G.ALPHA.13 Induces PreproET-1 Gene Expression via JNK.

et al. 2002

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“…The femoral vein was cannulated for the administration of salusins, and a saline-filled PE50 polyethylene catheter placed in the femoral artery was connected to a pressure transducer for continuous recordings of blood pressure and heart rate (HR) as described. 6 An electromagnetic flow probe was attached to the abdominal aorta to estimate arterial blood flow (ABF) with an electromagnetic flowmeter (MFV-1100; Nihon Koden). Data were acquired with a polygraph (RM-6000; Nihon Koden).…”

Section: Effects Of the Intravenous Infusion Of Salusins On The Hemodmentioning

confidence: 99%

Synthetic Salusins as Cardiac Depressors in Rat

et al. 2005

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Abstract-Using bioinformatic analyses of full-length, enriched human cDNA libraries, we recently identified salusins, multifunctional related peptides ubiquitously expressed in major human tissues. Salusins cause transient and profound hypotension when injected intravenously to rats, the hypotensive effect of salusin-␤ being especially striking. However, the mechanisms of this hypotensive action remain elusive. To determine whether salusins modulate cardiac function in rats, we studied serial changes of systemic hemodynamics and functions of isolated perfused working and nonworking hearts before and after salusin administration. Intravenous salusin-␤ administration to intact anesthetized rats caused a temporary rapid, profound decrease in aortic blood flow concomitantly with hypotension and bradycardia without affecting systemic vascular resistance. Salusin-␤-induced hypotension and bradycardia were completely blocked by pretreatment with atropine, a muscarinic receptor antagonist, but not by propranolol. In isolated perfused working rat hearts, salusin-␤ significantly decreased cardiac output, aortic flow, and stroke work. However, it did not affect coronary flow in isolated working and nonworking hearts. Our results indicate that salusins induce potent hypotension via negative inotropic and chronotropic actions. Salusin-␤ promotes its actions by facilitating vagal outflows to the heart, whereas the negative inotropism of salusin-␤ is also mediated via a direct myotropic effect. Key Words: cardiac output Ⅲ heart rate Ⅲ blood pressure Ⅲ vascular resistance T he availability of a massive amount of information on human genome sequences has allowed for the faster elucidation of gene functions. Functional characterization of putative bioactive proteins is an indispensable process in elucidating the roles of secretory proteins. Very recently, we identified 2 novel multifunctional peptides of 28-and 20-residues that we designated as salusin-␣ and salusin-␤, respectively, 1 after screening a number of secretory proteinencoding cDNAs using receptor ligand-facilitated gene transfer protocols. 2,3 These salusins are considered to be generated simultaneously through proteolytic processing of prosalusin, a commonly occurring alternatively spliced product of the TOR2A gene, which has structural homologies to torsion dystonia genes (DYT1 and DQ1). 4,5 Alternative splicing responsible for biosynthesis of salusin peptides is probably not a rare event, and salusins are expressed ubiquitously throughout human tissues. 1 Systemic administration of salusins to rats is associated with rapid and profound hypotension and bradycardia; the maximal hypotensive response to salusin-␤ in rats is almost equivalent to or even exceeds those of the hypotensive peptide hormones identified thus far. Further, other potent endogenous hypotensive peptides do not induce hypotension and concomitant bradycardia with such a time course, implying an as yet undescribed mechanism for salusins. Although the expression of preprosalusin in heart is very limit...

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“…Firststrand cDNA from each mRNA was generated by a reverse transcription method using a First-Strand cDNA Synthesis Kit (Amersham Pharmacia Biotech, Piscataway, USA) (20). Rat and human iNOS mRNA was amplified using synthetic oligomers as probes (rat: forward 5 -GAAGGCTGGAACTA ACTGC-3 , complement 5 -TGCCTTGCTGAATGAACTT G-3 ; human, forward 5 -TACTCCACCAACAATGGCAA-3 , complement 5 -GATGAGCTGAGCATTCCACA-3 ), detected and quantified in real time using a Light Cycler TM (Roche Diagnostics, Basel, Switzerland), as previously described (21,22).…”

Section: Real-time Quantitative Reverse Transcription (Rt)-pcrmentioning

confidence: 99%