Cardiac effects of relaxin in rats

Kakouris, Hariclia; Eddie, Lawrence W.; Summers, Roger J.

doi:10.1016/0140-6736(92)90665-p

Cited by 116 publications

(89 citation statements)

References 5 publications

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“…Relaxin-treated mice had a smaller LV area and lower AVF, changes very likely due to a significantly increased heart rate level (Po0.05 vs MI þ VEH groups at days 7 and 30), a finding consistent with previous reports in other rodent models. 18,26 Hemodynamic measurements (Table 3) confirmed the relaxin-induced increment in heart rate at days 7 and 30 (Po0.01 vs sham and MI þ VEH groups). MI resulted in Figure 2).…”

Section: Functional Measurementsmentioning

confidence: 83%

“…It should be noted, however, that the dose of relaxin used (which produces circulating relaxin levels of 20-40 ng/ml; see Williams et al 19 and Samuel et al 20 ) significantly elevated HR, consistent with previous findings in other rodent models. 6,18,26 While interfering with some functional parameters that are sensitive to rate changes, such as Tau, a higher HR in treated animals would negatively impact on the infarcted heart. Again though, the relaxininduced higher level of HR did not appear to have any deleterious effects in the diseased heart, based on the similar extent of LV remodeling and dysfunction in MI þ RLX vs MI þ VEH mice, matched by IS.…”

Section: Discussionmentioning

confidence: 99%

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Relaxin remodels fibrotic healing following myocardial infarction

Samuel

Cendrawan

Gao

et al. 2011

Laboratory Investigation

101

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In the setting of myocardial infarction (MI), implanted stem cell viability is low and scar formation limits stem cell homing, viability, and integration. Thus, interventions that favorably remodel fibrotic healing may benefit stem cell therapies. However, it remains unclear whether it is feasible and safe to remodel fibrotic healing post-MI without compromising ventricular remodeling and dysfunction. This study, therefore, determined the anti-fibrotic and other effects of the hormone, relaxin in a mouse model of MI. Adult male mice underwent left coronary artery ligation-induced MI and were immediately treated with recombinant human relaxin (MI þ RLX) or vehicle (MI þ VEH) over 7 or 30 days, representing time points of early and mature fibrotic healing. Cardiac function was assessed by echocardiography and catheterization, while comprehensive immunohistochemistry, morphometry, and western blotting were performed to explore the relaxin-induced mechanisms of action post-MI. RLX significantly inhibited the MI-induced progression of cardiac fibrosis over 7 and 30 days, which was associated with a reduction in TGF-b1 expression, myofibroblast differentiation, and cardiomyocyte apoptosis in addition to a promotion of matrix metalloproteinase-13 levels and de novo blood vessel growth (all Po0.05 vs respective measurements from MI þ VEH mice). Despite the evident fibrotic healing post-MI, relaxin did not adversely affect the incidence of ventricular free-wall rupture or the extent of LV remodeling and dysfunction. These combined findings demonstrate that RLX favorably remodels the process of fibrotic healing post-infarction by lowering the density of mature scar tissue in the infarcted myocardium, border zone, and non-infarcted myocardium, and may, therefore, facilitate cell-based therapies in the setting of ischemic heart disease.

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Section: Functional Measurementsmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Relaxin remodels fibrotic healing following myocardial infarction

Samuel

Cendrawan

Gao

et al. 2011

Laboratory Investigation

101

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“…Moreover, RLX has been reported to decrease blood pressure and to blunt the response to vasoconstrictors in mesenteric vasculature in spontaneously hypertensive rats (St-Louis & Massicotte, 1985;Massicotte et al, 1989). RLX has also been found to have positive chronotropic and inotropic effects on the rat heart (Parry et al, 1990;Kakouris et al, 1992;Ward et al, 1992), most likely by binding to high affinity specific receptors in the heart atria (Osheroff et al, 1992;Osheroff & Ho, 1993). More recently, cardiocytes derived from the atria of rats have been shown to secrete detectable amounts of RLX (Taylor & Clark, 1994), which it has been suggested may act via autocrine and/ or paracrine routes to regulate cardiovascular structure and function, thus strengthening the idea that the heart is a physiological target organ for RLX.…”

Section: Introductionmentioning

confidence: 99%

“…More recently, cardiocytes derived from the atria of rats have been shown to secrete detectable amounts of RLX (Taylor & Clark, 1994), which it has been suggested may act via autocrine and/ or paracrine routes to regulate cardiovascular structure and function, thus strengthening the idea that the heart is a physiological target organ for RLX. Based on these cardiac effects of RLX, some authors (Kakouris et al, 1992) have suggested that the hormone may be responsible for the elevation of cardiac output during human pregnancy (Durr, 1989), when serum concentrations of RLX also become elevated (Bell et al, 1987). In this study we aimed to clarify whether RLX influences the vascular tone of the coronary system by determining the coronary flow in isolated, perfused hearts of the guinea-pig and rat.…”

Section: Introductionmentioning

confidence: 99%

Relaxin‐induced increased coronary flow through stimulation of nitric oxide production

Bani-Sacchi

Bigazzi²,

Bani

et al. 1995

British J Pharmacology

152

125

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1 Relaxin (RLX) is a multifunctional hormone which, besides its role in pregnancy and parturition, has also been shown to influence the cardiovascular system. In this study, we investigated the effect of RLX on coronary flow of rat and guinea-pig hearts, isolated and perfused in a Langendorff apparatus. RLX was either added to the perfusion fluid at a concentration of 5 x 109 M for a 20-min perfusion, or given as a bolus into the aortic cannula at concentrations of 10-9 M, 5 x io-9 M and 10-8 M dissolved in 1 ml of perfusion fluid. 2 RLX, given either for a 20-min perfusion or as a bolus in the aortic cannula to guinea-pig and rat isolated hearts, increased the coronary flow and the amount of nitrite, a stable end-product of nitric oxide (NO) metabolism, that appeared in the perfusates in a concentration-dependent fashion. 3 The increase in coronary flow and in nitrite in the perfusates induced by RLX was significantly reduced by pretreatment with the nitric oxide synthase (NOS) 4 The effects of RLX on coronary flow and nitrite amounts in the perfusates were compared with those induced by the endothelium-dependent vasodilator agent, acetylcholine (ACh, I0--I0-M), and by the endothelium-independent vasodilator agent, sodium nitroprusside (SNP, I0--10-6 M). The results obtained show that RLX is more effective than ACh and SNP in increasing coronary flow. 5 The results of this study show that RLX increases coronary flow through stimulation of NO production; hence this hormone should be regarded as a novel agent capable of improving myocardial perfusion.

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“…1). It exerts a positive, potent and dose-dependent chronotropic effect in the heart [10][11][12] and increases heart rate in the perfused intact heart [13][14][15][16]. In rat atria, relaxin produces greater cardioprotective effects than angiotensin II, adrenaline, endothelin-1, isoprenaline, serotonin or histamine [11].…”

Section: Introductionmentioning

confidence: 99%

Relaxin: A Magical Therapy for Healthy Heart

Waza

Bhat

Hamid

2018

Int J Curr Pharm Sci

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Relaxin (a peptide hormone) has emerged as a cardio protective agent and plays a vital role in normal cardiac function. By activation a complex network of signalling cascade, relaxin is responsible for creating a healthy environment for heart functioning. Under pathological conditions, such as cardiomyopathy and heart failure, the expression level of relaxin is increased dramatically to protect the heart. By promoting angiogenesis, vasodilatation, improving ischemia/reperfusion injury and remodeling, relaxin has emerged as a magical agent to address cardiac abnormalities. Over the past 3 decades, various cardio protection strategies are in use to deal with cardiac diseases, however, till date, no effective therapy is in clinical practice. Relaxin has emerged as a novel therapeutic agent to have beneficial action during various pathological conditions. In this review, we have discussed different cardio protective roles of relaxin that marks it, as an effective agent to tackle heart-related diseases.

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Cardiac effects of relaxin in rats

Cited by 116 publications

References 5 publications

Relaxin remodels fibrotic healing following myocardial infarction

Relaxin remodels fibrotic healing following myocardial infarction

Relaxin‐induced increased coronary flow through stimulation of nitric oxide production

Relaxin: A Magical Therapy for Healthy Heart

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