Time course and dose response of relaxin-mediated renal vasodilation, hyperfiltration, and changes in plasma...

The pregnancy hormone relaxin elicits renal vasodilation, hyperfiltration, and osmoregulatory changes when chronically administered to conscious, nonpregnant rats. The objective in this study was to determine the dose response and time course of hormone action, as well as the time required for recovery on stopping its administration. The threshold dose of recombinant human relaxin (rhRLX) for renal vasodilation and reduction in plasma osmolality was 0.15 microg/h when given by subcutaneous osmotic minipump for 2 days (an infusion rate that achieved circulating levels of approximately 6 ng/ml). The peak response was observed during the 0.4 microg/h infusion rate (serum rhRLX of approximately 11 ng/ml), which was comparable to our previous work using a 4.0 microg/h (serum rhRLX of approximately 20 ng/ml). In contrast, a dose of 40 microg/h was ineffective (serum rhRLX of approximately 80 ng/ml). When 4.0 microg/h rhRLX was administered by osmotic minipump for shorter periods (