Relaxin is well known for its actions on collagen remodeling. To improve our understanding of the physiologic role(s) of relaxin, the relaxin gene-knockout (RLX-KO) mouse was established by our group and subsequently phenotyped. Pregnant RLX-KO mice underwent inadequate development of the pubic symphysis as well as the mammary glands and nipples compared to wild-type mice, thus preventing lactation. Later studies showed that these deficiencies were associated with increased collagen, primarily in the nipple and vagina. Analysis of male RLX-KO mice also demonstrated inadequate reproductive tract development. The testis, epididymis, and prostate of RLX-KO mice showed delayed tissue maturation and growth associated with increased collagen deposition. In nonreproductive tissues, an age-related increase in interstitial collagen (fibrosis) was also detected in the lung, heart, and kidneys of RLX-KO mice and was associated with organ dysfunction. From 6-9 months of age and onwards, all organs of RLX-KO mice, particularly male mice, underwent progressive increases in tissue weight and collagen content (all P < .05) compared with wild-type animals. The increased fibrosis contributed to bronchiole epithelium thickening and alveolar congestion (lung), atrial hypertrophy and increased ventricular chamber stiffness (heart) in addition to glomerulosclerosis (kidney). Treatment of RLX-KO mice with recombinant human relaxin in early and developed stages of fibrosis caused the reversal of collagen deposition in the lung, heart, and kidneys. Together, these findings suggest that relaxin is a naturally occurring inhibitor of collagen deposition during normal development, aging, and pregnancy and can be used to prevent the progression of fibrosis.

The influence of systemic or intracerebroventricular (icv) administration of angiotensin II on the intakes of NaCl solution, water, and food was investigated in BALB/c mice. Systemic administration of angiotensin II had little, if any, influence on these ingestive behaviors. On the other hand, icv infusion of angiotensin II at 70 ng/day increased (P less than 0.05) intakes of NaCl solution and water by the third day of infusion. The amount of NaCl ingested daily during the infusion was two to three times body sodium content. The mean daily water intake increased to 40-60% of body weight. The vast increase in NaCl intake was not secondary to a natriuresis caused by the icv infusion of angiotensin II. The results suggest that angiotensin II has a direct effect on neural systems involved in sodium appetite in this species.

A main vector of the effects of stress is secretion of corticotrophin releasing factor (CRF), adrenocorticotrophin (ACTH), and adrenal steroids. Systemic administration of ACTH (2.8 microgram/day sc) for 7 days in BALB/c mice caused a very large increase of voluntary intake of 0.3 M NaCl equivalent to turnover of total body sodium content each day. Intracerebroventricular infusion of ACTH (20 ng/day) had no effect. Intracerebroventricular infusion of ovine CRF (10 ng/h for 7 days) caused an increase of sodium intake. The large sodium appetite-stimulating effect of systemic ACTH was not influenced by concurrent systemic infusion of captopril (2 mg/day). Induction of stress by immobilization of mice on a running wheel caused an increase in Na appetite associated with a 50% decrease of thymus weight, indicative of corticosteroid effects. The present data suggest that stress and the hormone cascade initiated by stress evoke a large sodium appetite in mice, which may be an important survival mechanism in environmental conditions causing stress.