The kidneys and other nonreproductive organs vasodilate during early gestat
ion; however, the "pregnancy hormones" responsible for the profound vasodil
ation of the renal circulation during pregnancy are unknown. We hypothesize
d that the ovarian hormone relaxin (RLX) contributes. Therefore, ne tested
whether the administration of RLX elicits renal vasodilation and hyperfiltr
ation in conscious adult, intact female rats. After several days of treatme
nt with either purified porcine RLX or recombinant human RLX 2 (rhRLX), eff
ective renal plasma flow (ERPF) and glomerular filtration rate (GFR) increa
sed by 20%-40%. Comparable renal vasodilation and hyperfiltration was also
observed in ovariectomized rats, suggesting that estrogen and progesterone
are unnecessary for the renal response to rhRLX. The nitric oxide synthase
inhibitor N-omega-nitro-L-arginine methyl ester completely abrogated the in
crease in ERPF and GFR elicited by chronic administration of purified porci
ne RLX. In contrast, the renal vasoconstrictory response to angiotensin II
was attenuated by the RLX treatment. Short-term infusion of purified porcin
e RLX to conscious rats over several hours failed to increase ERPF and GFR
Plasma osmolality was consistently reduced by the chronic administration of
both RLX preparations. In conclusion, the renal and osmoregulatory effects
of chronic RLX administration to conscious rats resemble the physiological
changes of pregnancy in several respects: (a) marked increases in ERPF and
GFR with a mediatory role for nitric oxide; (b) attenuation of the renal c
irculatory response to angiotensin II; and (c) reduction in plasma osmolali
ty.