Unveiling the Vasodilatory Actions and Mechanisms of Relaxin

Conrad, Kirk P.

doi:10.1161/hypertensionaha.109.133926

Cited by 70 publications

(65 citation statements)

References 68 publications

(112 reference statements)

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“…Second, if relaxin directly induces vascular remodeling, then it is possible that there is a differential expression of the relevant relaxin receptor, relaxin/insulin-like family peptide 1 receptor (RXFP1), in various vascular beds. We and others (18,30) have previously observed arterial site-specific effects of relaxin regarding its ability to induce rapid relaxation but not for inhibition of myogenic reactivity that applies to all artery-types studied so far (5,9). However, further studies are necessary to identify the mechanisms underlying the site-specific effects of relaxin.…”

Section: Site-specific Effects Of Relaxinmentioning

confidence: 90%

Relaxin regulates vascular wall remodeling and passive mechanical properties in mice

Debrah

Haney

et al. 2011

Journal of Applied Physiology

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Administration of recombinant human relaxin (rhRLX) to conscious rats increases global arterial compliance, and small renal arteries (SRA) isolated from these rats demonstrate increased passive compliance. Here we characterize relaxin-induced vascular remodeling and examine its functional relevance. SRA and external iliac arteries (EIA) were examined in rhRLX-treated (1.0 g/h for 5 days) and relaxin knockout mice. Arterial geometric remodeling and compositional remodeling were quantified using immunohistochemical and biochemical techniques. Vascular mechanical properties were quantified using an ex vivo preparation wherein pressure-diameter data were obtained at various axial lengths. Compared with vehicle-treated mice, SRA from rhRLX-treated mice showed outward geometric remodeling (increased unstressed wall area and wall-to-lumen area ratio), increased smooth muscle cell (SMC) density, reduction in collagen-to-total protein ratio, and unchanged elastin-to-tissue dry weight ratio. Compared with wild-type mice, relaxin knockout mice exhibited the opposite pattern: decreased unstressed wall area and wall-to-lumen area ratio, decreased SMC density, and increased collagen-to-total protein ratio. Although tissue biaxial strain energy of SRA was not different between rhRLX-and vehicle-treated groups at low-to-physiological circumferential and axial strains, it was lower for the rhRLX-treated group at the highest circumferential strain. In contrast to SRA, relaxin administration was not associated with any vascular remodeling or changes in passive mechanics of EIA. Thus relaxin induces both geometric and compositional remodeling in vessel-specific manner. Relaxin-induced geometric remodeling of SRA is responsible for the increase in passive compliance under low-to-physiological levels of circumferential and axial strains, and compositional remodeling becomes functionally relevant only under high circumferential strain. arterial compliance; arterial collagen; elastin; smooth muscle; matrix metalloproteinase-2; relaxin knockout mice RELAXIN IS A 6-KDA PEPTIDE hormone that emanates from the corpus luteum and circulates during the luteal phase of the menstrual cycle and in pregnancy (42). Traditionally, the hormone has been associated with the female reproductive tract, but recent evidence indicates that relaxin plays an important role in cardiovascular function (reviewed in Refs. 7, 28). We found that administration of recombinant human relaxin (rhRLX) to chronically instrumented, nonpregnant female and male rats increased cardiac output and global arterial compliance (AC), as well as decreased systemic vascular resistance (6,13,14). Concurrent with relaxin's influence on overall cardiovascular function, small renal arteries isolated from the rhRLX-treated, nonpregnant female rats demonstrated increased passive compliance (6). More recently, we explored the role of endogenous, vascular-derived relaxin in modifying arterial mechanical properties in mice. We observed that small renal arteries isolated from relaxin knockout...

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Section: Site-specific Effects Of Relaxinmentioning

confidence: 90%

Relaxin regulates vascular wall remodeling and passive mechanical properties in mice

Debrah

Haney

et al. 2011

Journal of Applied Physiology

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“…These include increases in cardiac output, heart rate, and a decrease in vascular Relaxin Family Peptide Receptors resistance Debrah et al, 2005Debrah et al, , 2006. Increases in plasma volume and decreased blood pressure are not consistently observed (Ahokas et al, 1989;Conrad, 2004Conrad, , 2010Conrad, , 2011. Ovariectomy or passive immunization with monoclonal antibodies for rat relaxin prevent these adaptive changes (Novak et al, 2001).…”

Section: Physiologic Roles Of Relaxin Family Peptide Receptors Andmentioning

confidence: 99%

“…Relaxin is a potent vasodilator in arteries (Conrad, 2010;McGuane et al, 2011b), although the effect is vessel specific (McGuane et al, 2011b). Relaxin is a physiologic antagonist of vasoconstrictors in mesenteric arteries (St-Louis and Massicotte, 1985;Massicotte et al, 1989), primary bovine aortic smooth muscle cells (Bani et al, 1998a), and uterine artery (Longo et al, 2003).…”

Section: Physiologic Roles Of Relaxin Family Peptide Receptors Andmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

Halls¹,

Bathgate²,

Sutton³

et al. 2015

Pharmacol Rev

118

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“…Moreover, the serum levels of RLX-2 were not associated with the severity of the coronary lesions in UA patients with glucose metabolism dysfunction. Although previous studies have proposed the potential cardioprotective role of RLX-2 as evidenced by attenuation of cardiac remodeling 30) and improving endothelial function, 31) the association between RLX-2 and severity of coronary lesions were not intensively studied. Our study is the first to evaluate the potential association between serum RLX-2 and coronary arterial lesion severity in UA patients with glucose metabolism dysfunction.…”

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confidence: 99%

Decreased Serum Relaxin-2 Is Correlated with Impaired Islet β-Cell Function in Patients with Unstable Angina and Abnormal Glucose Metabolism

Gao

Wang

et al. 2018

Int. Heart J.

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SummaryCirculating relaxin (RLX) is altered in patients with diabetes mellitus (DM) or cardiovascular diseases. This study was designed to evaluate the changes of RLX in patients with unstable angina (UA) complicated with various categories of abnormal glucose metabolism.Patients who confirmed UA by angiographic and clinical standard were grouped according to the glucose metabolism status with oral glucose tolerance test (OGTT) and medical history categorized as normal, prediabetes, newly diagnosed type 2 DM (T2DM), and previously diagnosed T2DM. Serum RLX-2 was measured and islet β-cell function was evaluated. The severity of the coronary arterial lesions was evaluated with Syntax Scores.Serum RLX-2 was significantly higher in UA patients with prediabetes (median [quartiles]: 9.87 [7.48, 32.58] pg/mL) and newly diagnosed T2DM (18.36 [9.52, 48.08] pg/mL), compared with those with normal glucose tolerance (6.24 [4.02, 7.27] pg/mL, both P < 0.05). Interestingly, UA patients with previously diagnosed T2DM exhibited lower RLX-2 levels (4.17 [3.23, 5.72] pg/mL) compared with those with normal glucose tolerance (P < 0.05). Subsequent analyses indicated that serum RLX-2 was positively associated with parameters of islet β-cell function, C-peptide, and fasting insulin levels; however, it was negatively associated with the levels of fasting glucose, 2-hour postprandial blood glucose, HbA1c, and insulin sensitivity, suggesting a potential protective role of RLX-2 during abnormal glucose metabolism in UA patients. Serum RLX-2 was not correlated with the Syntax Scores in these patients.Serum RLX-2 is a potential marker for UA patients with early glucose metabolism abnormality, and increased RLX-2 level was correlated with preserved islet β-cell function.(Int Heart J Advance Publication)

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Unveiling the Vasodilatory Actions and Mechanisms of Relaxin

Cited by 70 publications

References 68 publications

Relaxin regulates vascular wall remodeling and passive mechanical properties in mice

Relaxin regulates vascular wall remodeling and passive mechanical properties in mice

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

Decreased Serum Relaxin-2 Is Correlated with Impaired Islet β-Cell Function in Patients with Unstable Angina and Abnormal Glucose Metabolism

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