Radioimmunoassay of Relaxin in Pregnancy With an Analogue of Human Relaxin

Eddie, Lawrence W.; Lester, Arlene R.; Bennett, Gregory L.; Bell, Robin Jean; Geier, Michael; Johnston, Paul D.; Niall, Hugh D.

doi:10.1016/s0140-6736(86)91662-4

Cited by 74 publications

(46 citation statements)

References 9 publications

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“…These changes, in turn, can influence liver metabolism, as can be argued by our findings on the hepatocytes of the same RLX-treated rats as those studied here (Bani et al 2001). In this context, the ability of RLX to increase hepatic circulation may be of some physiologic relevance during pregnancy when this hormone attains the highest plasma levels (Eddie et al 1986). By this mechanism, RLX may participate in the metabolic changes of the liver occurring in pregnancy, which are directed to fulfil the fuel needs of the placenta and the conceptus (Paul 1972, Herrera & Freinkel 1975, Baumann et al 1981, Everson 1998, Freetly & Ferrel 1998.…”

Section: Discussionsupporting

confidence: 64%

The vasorelaxant hormone relaxin induces changes in liver sinusoid microcirculation: a morphologic study in the rat

Bani

Nistri²,

Quattrone³

et al. 2001

Journal of Endocrinology

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This study shows that specialized contractile endothelial cells exist in rat liver sinusoids which may be involved in the local control of hemodynamics and which are sensitive to vasoactive agents, including the vasorelaxant hormone relaxin. Male rats were treated with 10 µg relaxin for 4 days; phosphate-buffered saline (PBS)-treated rats were the controls. For comparison, rats treated with relaxin together with the NO-synthase inhibitor N -nitro--arginine methyl ester (L-NAME), and rats treated with the vasodilator taurodeoxycholic acid or the vasoconstrictor ethanol were investigated. Liver fragments were studied morphologically and morphometrically. In the control rats, peculiar contractile cells were present in the endothelial lining. These cells had abundant myofilaments and formed cytoplasmic blebs projecting into and often occluding the lumen. In the ethanol-treated rats, sinusoids were constricted and filled with cytoplasmic blebs. In the relaxintreated rats, sinusoids were markedly dilated and the cytoplasmic blebs nearly disappeared. Similar findings were observed in the taurodeoxycholic acid-treated rats. The effects of relaxin were blunted by L-NAME, suggesting that the relaxin action involves an NO-mediated mechanism.

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Section: Discussionsupporting

confidence: 64%

The vasorelaxant hormone relaxin induces changes in liver sinusoid microcirculation: a morphologic study in the rat

Bani

Nistri²,

Quattrone³

et al. 2001

Journal of Endocrinology

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“…23 During human pregnancy, the maximum concentration of circulating relaxin occurs during the first trimester. 24 Within the rat, relaxin is not detected until day 10 of gestation and increases steadily during mid-gestation with a significant peak occurring at day 21. 25 A role for relaxin in mediating renal hemodynamic changes during pregnancy is suggested in a study by Danielson and Conrad wherein a chronic infusion of a physiologically relevant dose of human recombinant relaxin induces renal hemodynamic changes in nonpregnant rats comparable to that observed in mid-term pregnant rats.…”

Section: Discussionmentioning

confidence: 99%

Inducible Nitric Oxide Synthase Inhibition Attenuates Renal Hemodynamics During Pregnancy

et al. 2002

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Abstract-Acute, nonselective nitric oxide synthase inhibition in the pregnant rat decreases glomerular filtration rate and renal plasma flow, suggesting a role for nitric oxide in mediating renal vasodilation during pregnancy. As mid-gestation in the rat is associated with a significant increase in renal protein expression of inducible nitric oxide synthase, the aim of this study was to examine the role of inducible nitric oxide synthase in mediating renal hemodynamics changes at mid-gestation in the rat. At day 16 of pregnancy, glomerular filtration rate was significantly higher in pregnant rats compared with virgin rats (3.1Ϯ0.4 versus 2.7Ϯ0.3 mL/min, respectively; PϽ0.05), as was effective renal plasma flow (13.4Ϯ2.5 versus 10.9Ϯ2.2 mL/min, respectively; PϽ0.05). Acute administration of the inducible nitric oxide synthase selective inhibitor, AMT hydrochloride (750 nmol/h), markedly attenuated the increase in glomerular filtration rate observed in pregnant rats (2.3Ϯ0.2 mL/min, PϽ0.01 versus pregnant) without significantly altering glomerular filtration rate in virgin rats (2.1Ϯ0.2 mL/min). Acute AMT administration significantly decreased effective renal plasma flow in pregnant (8.9Ϯ1.8 mL/min, PϽ0.01 versus pregnant) and virgin rats (7.1Ϯ0.9 mL/min, PϽ0.05 versus virgin). Acute administration of EIT (380 nmol/h), another inducible nitric oxide synthase selective inhibitor, also attenuated pregnancy-induced increases in glomerular filtration rate (2.1Ϯ0.2, 2.8Ϯ0.3, and 2.3Ϯ0.3 mL/min; virgin, pregnant, and EIT, respectively) and effective renal plasma flow (8.5Ϯ1.1, 13.8Ϯ2.1, and 9.0Ϯ1.1 mL/min; virgin, pregnant, and EIT, respectively). Therefore, these findings suggest that inducible nitric oxide synthase may play an important role in mediating the renal hemodynamic changes that occur during normal pregnancy. Key Words: pregnancy Ⅲ nitric oxide synthase Ⅲ kidney Ⅲ hemodynamics Ⅲ rats N ormal pregnancy is associated with significant increases in renal hemodynamics as increases in glomerular filtration rate (GFR) and renal plasma flow (RPF) of Ͼ40% are observed in pregnant women. 1 In the rat, GFR and RPF are increased by Ͼ20% at mid-gestation with a return to prepregnant values by late pregnancy. 2,3 These increases in renal hemodynamics at mid-gestation in the rat are associated with significant increases in whole-body nitric oxide (NO) production 3,4 and renal protein expression of both inducible and neuronal nitric oxide synthase (iNOS and nNOS, respectively). 3 A role for NO in mediating renal vasodilation during pregnancy is suggested in a study by Danielson and Conrad in which acute nonselective NOS inhibition equalized GFR and effective RPF (ERPF) in virgin rats and pregnant rats at mid-gestation. 5 However, nonselective inhibition of all three NOS isoforms, endothelial (eNOS), neuronal (nNOS), and inducible (iNOS), does not elucidate which specific isoform is an important source of NO during pregnancy.Several lines of evidence suggest that NO generated by the iNOS isoform may play an important role in...

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“…The first identified role for relaxin was in pregnancy, as the circulating levels of relaxin, produced by the corpus luteum of the ovary, peak during the first trimester. 71 During pregnancy, relaxin is thought to have a role in implantation, as well as other species-dependent functions. 69 One other important role attributed to relaxin is in the cardiovascular events that occur in pregnancy.…”

Section: Serelaxinmentioning

confidence: 99%

Current treatments for acute heart failure: focus on serelaxin

Bennett¹

2014

RRCC

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Acute heart failure remains an enormous health concern worldwide, and is a major cause of death and hospitalization. In spite of this, the treatment strategies for acute heart failure have remained largely unchanged for the past 2 decades. Several large randomized, placebocontrolled clinical trials have recently been conducted to attempt to improve the treatment and outcomes of acute decompensated heart failure. Some studies, including the EVEREST (tolvaptan) and ASCEND (nesiritide) showed efficacy at relieving early symptoms, but failed to improve long-term outcomes. Others, including PROTECT (rolofylline) and ASTRONAUT (aliskiren) showed little benefit in the relief of early symptoms or long-term outcomes. The recent RELAX-AHF studies using serelaxin, a recombinant form of relaxin, have shown considerable promise. Importantly, serelaxin improved congestion (dyspnea) and other early targets of acute decompensated heart failure treatment, but also improved mortality at 180 days. The purpose of this review is to provide an overview of current treatment strategies for acute decompensated heart failure, and a discussion of the recent clinical trials, with an emphasis on the serelaxin studies.

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Radioimmunoassay of Relaxin in Pregnancy With an Analogue of Human Relaxin

Cited by 74 publications

References 9 publications

The vasorelaxant hormone relaxin induces changes in liver sinusoid microcirculation: a morphologic study in the rat

The vasorelaxant hormone relaxin induces changes in liver sinusoid microcirculation: a morphologic study in the rat

Inducible Nitric Oxide Synthase Inhibition Attenuates Renal Hemodynamics During Pregnancy

Current treatments for acute heart failure: focus on serelaxin

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