Relaxin is essential for renal vasodilation during pregnancy in conscious rats

被引:164
作者
Novak, J
Danielson, LA
Kerchner, LJ
Sherwood, OD
Ramirez, RJ
Moalli, PA
Conrad, KP
机构
[1] Magee Womens Res Inst, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA
[3] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA
[4] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA
[5] Univ Illinois, Coll Med, Urbana, IL 61801 USA
[6] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15260 USA
关键词
D O I
10.1172/JCI11975
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Marked vasodilation in the kidney and other nonreproductive organs is one of the earliest maternal adaptations to occur during pregnancy. Despite the recognition of this extraordinary physiology for over four decades, the gestational hormone responsible has remained elusive. Here we demonstrate a key role for relaxin, a member of the IGF family that is secreted by the corpus luteum in humans and rodents. Using a gravid rodent model, we employ two approaches to eliminate relaxin or its biological activity from the circulation: ovariectomy and administration of neutralizing antibodies. Both abrogate the gestational elevation in renal perfusion and glomerular filtration, as well as preventing the reduction in myogenic reactivity of isolated, small renal arteries. Osmoregulatory changes, another pregnancy adaptation, are also abolished. Our results indicate that relaxin mediates the renal vasodilatory responses to pregnancy and thus may be important for maternal and fetal health. They also raise the likelihood of a role for relaxin in other cardiovascular changes of pregnancy, and they suggest that, like estrogen, relaxin should be considered a regulator of cardiovascular function.
引用
收藏
页码:1469 / 1475
页数:7
相关论文
共 39 条
[21]  
GAGNON J, 1989, SUPERANOVA, P199
[22]   Endothelin and nitric oxide mediate reduced myogenic reactivity of small renal arteries from pregnant rats [J].
Gandley, RE ;
Conrad, KP ;
McLaughlin, MK .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2001, 280 (01) :R1-R7
[23]   SYSTEMIC HEMODYNAMICS AND OXYGEN-TRANSPORT DURING PREGNANCY IN CHRONICALLY INSTRUMENTED, CONSCIOUS RATS [J].
GILSON, GJ ;
MOSHER, MD ;
CONRAD, KP .
AMERICAN JOURNAL OF PHYSIOLOGY, 1992, 263 (06) :H1911-H1918
[24]   STEROID EFFECTS ON RELAXIN SECRETION IN THE RAT [J].
GOLDSMITH, LT ;
DELACRUZ, JL ;
WEISS, G ;
CASTRACANE, VD .
BIOLOGY OF REPRODUCTION, 1982, 27 (04) :886-890
[25]   QUANTITATIVE-ANALYSIS OF PHYSIOLOGICAL-ROLE OF ESTRADIOL AND PROGESTERONE IN CONTROL OF TONIC AND SURGE SECRETION OF LUTEINIZING-HORMONE IN RAT [J].
GOODMAN, RL .
ENDOCRINOLOGY, 1978, 102 (01) :142-150
[26]  
GUICO MSL, 1985, J REPROD FERTIL, V74, P65
[27]   MONOCLONAL-ANTIBODIES SPECIFIC FOR RAT RELAXIN .1. PRODUCTION AND CHARACTERIZATION OF MONOCLONAL-ANTIBODIES THAT NEUTRALIZE RAT RELAXINS BIOACTIVITY INVIVO [J].
GUICOLAMM, ML ;
VOSS, EW ;
SHERWOOD, OD .
ENDOCRINOLOGY, 1988, 123 (05) :2472-2478
[28]   TIME COURSE OF SERUM ESTROGEN AND LUTEINIZING HORMONE (LH) CONCENTRATIONS DURING MENSTRUAL CYCLE OF RHESUS MONKEY [J].
HOTCHKIS.J ;
ATKINSON, LE ;
KNOBIL, E .
ENDOCRINOLOGY, 1971, 89 (01) :177-&
[29]   MONOCLONAL-ANTIBODIES SPECIFIC FOR RAT RELAXIN .4. PASSIVE-IMMUNIZATION WITH MONOCLONAL-ANTIBODIES DURING THE ANTEPARTUM PERIOD REDUCES CERVICAL GROWTH AND EXTENSIBILITY, DISRUPTS BIRTH, AND REDUCES PUP SURVIVAL IN INTACT RATS [J].
HWANG, JJ ;
SHANKS, RD ;
SHERWOOD, OD .
ENDOCRINOLOGY, 1989, 125 (01) :260-266
[30]  
Lindheimer M D, 1981, Contrib Nephrol, V25, P71