Table 1.

Cardiovascular effects of relaxin treatment under hyperglycemic conditions.

Duration; dose; route	Vascular effects	References
6.5 h; 15 μg/h; jugular vein	Mouse aorta: Increased carbachol-evoked relaxation in lean but not high fat-fed mice.	Bonner et al., 2013
3 weeks; 1 mg/kg/d; subcutaneous	Increased carbachol-evoked relaxation in high fat-fed mice.
72 h; 10 nM; in vitro	Mouse aorta: Prevented high glucose (30 mM)-induced endothelial dysfunction by increasing vasodilator prostacyclin and counteracting superoxide production.	Ng et al., 2016
2 weeks; 0.5mg/kg/d; subcutaneous	Mouse aorta: Increased nitric oxide-mediated ACh-evoked relaxation in STZ-induced diabetic mice. Mouse mesenteric artery: Reversed diabetes-induced endothelial dysfunction by increasing nitric oxide-mediated relaxation, normalizing the contribution of vasoconstrictor prostanoids, and reducing vasoconstrictor response to AngII.	Ng et al., 2017
30 min; 100 ng/mL; in vitro	Rat ventricular myocyte: Prevented high glucose (33 mM)-induced apoptosis and endoplasmic reticulum stress by reducing CHOP, cleaved caspase-8, -9, and -12 protein expression.	Zhang et al., 2015
48 h; 100 ng/mL; in vitro	Rat fibroblast: Inhibited high glucose (33 mM)-induced oxidative stress and collagen synthesis by decreasing collagen I and III, α-SMA, P2X7R-mediated NLRP3 inflammasome activation, IL-18, IL-1β, and cleaved caspase-1 expression.	Zhang et al., 2018
48 h; 0.1 mM; in vitro	Rat H9c2 cell line: Reduced high glucose (33 mM)-induced cardiomyocyte hypertrophy, oxidative stress and apoptosis by decreasing ANP, BNP, caspase-3, cytochrome C protein expression, and increasing Notch1, Hes1, and MnSOD expression.	Wei et al., 2018
72 h; 100 ng/mL; in vitro	Rat fibroblast: Reduced high glucose (25 mM)-induced fibroblast proliferation, procollagen I and III, and MMP2 and MMP9 production.	Wang et al., 2009
2 weeks; 0.5 mg/kg/d; subcutaneous	Rat left ventricle: Improved diastolic function and decreased myocardial stiffness by reducing α-SMA, TIMP-1 and increasing MMP-13 expression in STZ-induced transgenic mRen-2 rats.	Samuel et al., 2008
2 weeks; 2 μg/kg/d; subcutaneous	Rat left ventricle: Improved function by mitigating diabetes-induced apoptosis, fibrosis and inflammasome activation in STZ-induced diabetic rats.	Zhang et al., 2017
2 weeks; 0.5 mg/kg/d; subcutaneous	Mouse left ventricle: Suppressed hypertrophy and apoptosis through a reduction in BNP and Bax:Bcl2 expression in STZ-induced diabetic mice.	Ng et al., 2017

ACh, acetylcholine; AngII, angiotensin II; STZ, streptozotocin; CHOP, C/EBP homologous protein; α-SMA, alpha smooth muscle actin; P2X7R, ionotropic purinergic receptor; NLRP3, nucleotide-binding domain and leucine-rich repeat-containing family, pyrin domain containing 3; IL, interleukin; ANP, atrial natriuretic peptide; BNP, B-type natriuretic peptide; Hes1, hairy and enhancer of split-1; MnSOD, manganese superoxide dismutase; MMP, matrix metalloproteinase; TIMP, tissue inhibitor of metalloproteinase; Bcl2, B-cell lymphoma 2; Bax, Bcl2-associated X protein.