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

Abstract

We previously showed that chronic administration of recombinant human relaxin (rhRLX; 4 μg/h) to conscious female, nonpregnant rats to reach serum levels corresponding to early to midgestation (∼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 μg/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 μg/h) administered to nonpregnant female rats yielding serum concentrations corresponding to late pregnancy (∼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. With respect to baseline, chronic rhRLX administration to male rats over 10 days at 4 μg/h increased both CO (20.5 ± 4.2%) and AC (19.4 ± 6.9%) and reduced SVR (12.7 ± 3.9%). These results were comparable to those elicited by the hormone in nonpregnant female rats. In contrast, neither acute (over 4 h) nor chronic (over 6 days) infusion of the higher dose of rhRLX administered to conscious female rats resulted in significant changes in CO, AC, or SVR from baseline. We conclude that 1) rhRLX increases CO and AC and reduces SVR irrespective of sex, and 2) the rhRLX dose response is biphasic insofar as significant alterations in CO and systemic arterial load fail to occur at high serum concentrations.