| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131; and 2Departments of Obstetrics, Gynecology, and Reproductive Sciences, and Cell Biology and Physiology, University of Pittsburgh School of Medicine and Magee-Womens Research Institute, Pittsburgh, Pennsylvania 15213
Submitted 22 May 2003 ; accepted in final form 18 June 2003
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 µg/h when given by subcutaneous osmotic minipump for 2 days (an infusion rate that achieved circulating levels of 
6 ng/ml). The peak response was observed during the 0.4 µg/h infusion rate (serum rhRLX of 11 ng/ml), which was comparable to our previous work using a 4.0 µg/h (serum rhRLX of 20 ng/ml). In contrast, a dose of 40 µg/h was ineffective (serum rhRLX of 80 ng/ml). When 4.0 µg/h rhRLX was administered by osmotic minipump for shorter periods (
24 h), renal circulatory and osmoregulatory changes were observed by 6 h. After removal of the osmotic minipump, these changes persisted for at least 12 h, but they were fully restored by 24 h. Even briefer administration of 4.0 µg/h rhRLX by intravenous infusion showed an onset of action in the kidney by 1-2 h. In contrast, the 40 µg/h dose of rhRLX elicited minimal effects, and comparable to our earlier report, 4.0 µg/h purified porcine relaxin was also relatively ineffective during short-term intravenous administration. In conclusion, the effect of relaxin on the renal circulation and osmoregulation is biphasic, insofar as high doses are relatively inactive, and the onset of action is more rapid than previously believed. These findings may be important to consider when evaluating relaxin in the treatment of renal disease.
glomerular filtration; renal circulation; pregnancy
This article has been cited by other articles:
|
|
 |
|
  T.-Y. Ho, W. Yan, and C. A. Bagnell Relaxin-induced matrix metalloproteinase-9 expression is associated with activation of the NF-{kappa}B pathway in human THP-1 cells J. Leukoc. Biol., May 1, 2007; 81(5): 1303 - 1310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jeyabalan, J. Novak, K. D. Doty, J. Matthews, M. C. Fisher, L. J. Kerchner, and K. P. Conrad Vascular Matrix Metalloproteinase-9 Mediates the Inhibition of Myogenic Reactivity in Small Arteries Isolated from Rats after Short-Term Administration of Relaxin Endocrinology, January 1, 2007; 148(1): 189 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Smith, Lee. A. Danielson, Kirk. P. Conrad, and J. M. Davison Influence of Recombinant Human Relaxin on Renal Hemodynamics in Healthy Volunteers J. Am. Soc. Nephrol., November 1, 2006; 17(11): 3192 - 3197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M Sasser, M. D. Lindheimer, and C. Baylis An Emerging Role for Relaxin as a Renal Vasodilator J. Am. Soc. Nephrol., November 1, 2006; 17(11): 2960 - 2961. [Full Text] [PDF]
|
|
|
|
|
|
L. A. Danielson, A. Welford, and A. Harris Relaxin Improves Renal Function and Histology in Aging Munich Wistar Rats J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1325 - 1333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. O. Debrah, K. P. Conrad, A. Jeyabalan, L. A. Danielson, and S. G. Shroff Relaxin Increases Cardiac Output and Reduces Systemic Arterial Load in Hypertensive Rats Hypertension, October 1, 2005; 46(4): 745 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Kerchner, J. Novak, K. Hanley-Yanez, K. D. Doty, L. A. Danielson, and K. P. Conrad Evidence against the Hypothesis that Endothelial Endothelin B Receptor Expression Is Regulated by Relaxin and Pregnancy Endocrinology, June 1, 2005; 146(6): 2791 - 2797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. O. Debrah, K. P. Conrad, L. A. Danielson, and S. G. Shroff Effects of relaxin on systemic arterial hemodynamics and mechanical properties in conscious rats: sex dependency and dose response J Appl Physiol, March 1, 2005; 98(3): 1013 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Bogzil, R. Eardley, and N. Ashton Relaxin-induced changes in renal sodium excretion in the anesthetized male rat Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2005; 288(1): R322 - R328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. P. Conrad and J. Novak Emerging role of relaxin in renal and cardiovascular function Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2004; 287(2): R250 - R261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. P. Conrad, D. O. Debrah, J. Novak, L. A. Danielson, and S. G. Shroff Relaxin Modifies Systemic Arterial Resistance and Compliance in Conscious, Nonpregnant Rats Endocrinology, July 1, 2004; 145(7): 3289 - 3296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Heringlake, C. Heide, L. Bahlmann, W. Eichler, H. Pagel, P. Schmucker, R. Wergeland, F. P. Armbruster, and S. Klaus Effects of tilting and volume loading on plasma levels and urinary excretion of relaxin, NT-pro-ANP, and NT-pro-BNP in male volunteers J Appl Physiol, July 1, 2004; 97(1): 173 - 179. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
