Dissertation/Thesis Abstract

Relaxin regulates systemic hemodynamics and arterial wall mechanical properties
by Debrah, Dan Onwona, Ph.D., University of Pittsburgh, 2008, 222; 3335720
Abstract (Summary)

Relaxin is a peptide hormone emanating from the corpus luteum of the ovary which circulates during pregnancy. Although traditionally associated with female reproductive processes, recent evidence has suggested relaxin may play a vital role in regulating renal and cardiovascular function. Analogous to pregnancy, chronic administration of recombinant human relaxin (rhRLX) to nonpregnant female or male rats induces renal vasodilation and reduces the myogenic reactivity of small renal arteries (SRA). Additionally, elimination of circulating relaxin in pregnant rats with specific antibodies prevents the pregnancy associated changes in the renal circulation.

Based on these findings we postulated that relaxin exerts similar vasodilatory effects in the systemic circulation and examined its role in modulating systemic hemodynamics and vascular wall mechanical properties. Analogous to pregnancy, administration of rhRLX to nonpregnant female or male rats elicited increases in cardiac output and global arterial compliance, as well decreases in systemic vascular resistance. Additionally, neutralizing circulating relaxin in midpregnant rats eliminated the pregnancy associated changes in the systemic circulation.

In order to understand the mechanistic bases for the relaxin-induced increase in global arterial compliance, we examined the hormone’s effects on vascular wall remodeling. From a geometric perspective, SRA isolated from rhRLX-treated rats and mice were characterized by larger wall area resulting from relaxin-mediated smooth muscle cell (SMC) hyperplasia, and not hypertrophy. From a compositional perspective, these arteries were characterized by decreased collagen. Opposite results were obtained with removal of endogeneous relaxin: SRA from relaxin knock-out mice exhibited increased collagen content and decreased SMC density compared to wild-type mice. Finally, from a tissue mechanics perspective, SRA from rhRlx-treated mice exhibited strain-dependent reductions in tissue strain energy such that the greatest reduction was observed at the highest circumferential and axial strains.

We conclude that relaxin exerts systemic vasodilatory effects in both pregnant and nonpregnant states and in a gender-independent manner. Our findings indicate that the relaxin-induced increase in global arterial compliance is, at least in part, due to vascular wall compositional and geometric remodeling. Finally, our data indicate that the relaxin-induced compositional remodeling of SRA contributes to tissue mechanical properties under conditions of high circumferential and axial loads.

Indexing (document details)
Advisor:
Commitee:
School: University of Pittsburgh
School Location: United States -- Pennsylvania
Source: DAI-B 69/11, Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Physiology
Keywords: Arterial wall, Collagen, Elastin, Relaxin, Smooth muscle cells
Publication Number: 3335720
ISBN: 9780549894971
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