Relaxin regulates vascular wall remodeling and passive mechanical properties in mice.

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.

Role of relaxin in maternal systemic and renal vascular adaptations during gestation.

In this paper, the hemodynamic changes of normal pregnancy are reviewed and the underlying hormonal and molecular mechanisms are discussed. Among other findings related to these phenomena, our previous work has demonstrated the importance of relaxin in systemic and renal vascular as well as osmoregulatory changes during gestation. These findings are summarized, and new concepts related to the function of relaxin in blood vessels are presented.

Evidence for local relaxin ligand-receptor expression and function in arteries.

Relaxin is a 6 kDa protein hormone produced by the corpus luteum and secreted into the blood during pregnancy in rodents and humans. Growing evidence indicates that circulating relaxin causes vasodilatation and increases in arterial compliance, which may be among its most important actions during pregnancy. Here we investigated whether there is local expression and function of relaxin and relaxin receptor in arteries of nonpregnant females and males.

Relaxin is essential for systemic vasodilation and increased global arterial compliance during early pregnancy in conscious rats.

During early pregnancy, there are marked increases in cardiac output (CO) and global arterial compliance (AC), as well as decreases in systemic vascular resistance (SVR). We recently reported that administration of recombinant human relaxin to nonpregnant female rats elicits changes in systemic hemodynamics and arterial mechanical properties similar to those observed during normal pregnancy. In the present study, we directly tested whether endogenous relaxin mediates the cardiovascular adaptations of pregnancy by neutralizing circulating relaxin with monoclonal antibodies during early gestation.

Relaxin increases cardiac output and reduces systemic arterial load in hypertensive rats.

Chronic administration of recombinant human relaxin (rhRLX) to conscious, normotensive rats (male and female) increases cardiac output (CO) and global arterial compliance (ACg) and reduces systemic vascular resistance (SVR) with no change in mean arterial pressure (MAP). Effects (magnitude and temporal pattern) of relaxin on systemic hemodynamics and arterial properties in hypertensive animal models are not known. Accordingly, the major goal of the present study was to determine the cardiovascular effects of rhRLX in hypertensive rats using 2 models: Long-Evans rats chronically administered angiotensin II (AII) and spontaneously hypertensive rats (SHR).

Recombinant human relaxin (rhRLX) modifies systemic arterial properties in conscious rats irrespective of gender, but in a biphasic fashion.

Chronic administration of recombinant human relaxin (rhRLX) to conscious female nonpregnant rats that reaches serum concentrations of 10-30 ng/mL increases cardiac output and reduces systemic arterial load comparable to levels observed in midterm pregnancy. Chronic administration of the hormone to male rats increases cardiac output and reduces systemic arterial load to a similar extent. Short-term or chronic administration of rhRLX to conscious female rats that reaches serum concentrations of approximately 80 ng/mL results in minimal and insignificant changes.

Effects of relaxin on systemic arterial hemodynamics and mechanical properties in conscious rats: sex dependency and dose response.

We previously showed that chronic administration of recombinant human relaxin (rhRLX; 4 microg/h) to conscious female, nonpregnant rats to reach serum levels corresponding to early to midgestation (approximately 20 ng/ml) increases cardiac output (CO) and global arterial compliance (AC) and decreases systemic vascular resistance (SVR), comparable to changes observed in midterm pregnancy. The goals of this study were to test whether chronic administration of rhRLX (4 microg/h) to conscious male rats will yield similar changes in CO and systemic arterial load and to determine whether higher infusion rates of rhRLX (50 microg/h) administered to nonpregnant female rats yielding serum concentrations corresponding to late pregnancy ( approximately 80 ng/ml) will further modify CO and SVR and global AC comparable to late gestation. CO and systemic arterial load, as quantified by SVR and AC, were obtained by using the same methods as in our previous studies.

Troponin I protein kinase C phosphorylation sites and ventricular function.

Objective: Cardiac Troponin I (cTnI) phosphorylation by protein kinase C (PKC) results in a reduction of maximal actomyosin ATPase activity, an effect that is more marked at higher levels of calcium (Ca2+) and is likely to reduce active force development. We postulated that there would be greater Ca2+-dependent changes in ventricular function in hearts of cTnI transgenic (TG) mice expressing mutant troponin I lacking PKC sites compared to wild-type (WT).

Methods: We studied left ventricular function in isolated perfused hearts over a wide range of left ventricular volumes (Frank-Starling relationships) and mechanical restitution at three levels of perfusate Ca2+ (1.

Relaxin modifies systemic arterial resistance and compliance in conscious, nonpregnant rats.

Relaxin emanates from the corpus luteum of the ovary and circulates during pregnancy. Because the hormone is a potent renal vasodilator and mediates the renal vasodilation and hyperfiltration of pregnancy in conscious rats, we reasoned that it might also contribute to the broader cardiovascular changes of pregnancy. We began investigating this concept by testing whether relaxin can modify systemic arterial hemodynamics and load when chronically administered to nonpregnant rats.