From the Departments of Human Anatomy and Histology (D.B., T.B.S.) and of
Preclinical and Clinical Pharmacology (P.F., M.G.B., E.M.), University of
Florence; the Prosperius Institute (M.B.), Florence, Italy; and the William
Harvey Research Institute, London, UK (C.T.).
Correspondence to Prof Tatiana Bani Sacchi, Dipartimento di Anatomia Umana e Istologia, Sezione di Istologia, Viale G. Pieraccini 6, I-50139 Firenze, Italy. E-mail histology{at}cesit1.unifi.it
Abstract—The peptide hormone relaxin
(RLX) has been shown to elicit a powerful vasodilatory response in
several target organs. This response is mediated by the stimulation of
intrinsic nitric oxide (NO) generation. The present study was
designed to clarify whether RLX directly promotes the relaxation of
vascular smooth muscle cells through stimulation of NO generation.
Vascular smooth muscle cells from bovine aortas were incubated with RLX
at concentrations ranging from 1 nmol/L to 1 µmol/L. The
expression and activity of NO synthase, production of NO, and
the intracellular levels of cGMP and Ca2+ were determined.
The cell morphology and signal transduction mechanisms of these bovine
aortic smooth muscle cells in response to RLX were also studied. RLX
stimulated the expression of immunoreactive inducible NO synthase and
increased significantly and in a concentration-related fashion
inducible NO synthase activity, NO generation, and intracellular cGMP
levels. Concurrently, RLX significantly decreased cytosolic
Ca2+ concentrations and caused changes in cell shape and
the actin cytoskeleton that were consistent with cell
relaxation. The signal transduction mechanisms leading to the enhanced
expression of inducible NO synthase protein and activity caused by RLX
involve the activation of tyrosine kinase,
phosphatidylcholine–phospholipase C, and the transcription factor
nuclear factor-
© 1998 American Heart Association, Inc.
Scientific Contributions
Relaxin Activates the L-Arginine–Nitric Oxide Pathway in Vascular Smooth Muscle Cells in Culture
B, similar to bacterial endotoxins and
proinflammatory cytokines. This study suggests that RLX is an
endogenous agent capable of regulating vascular tone by
activation of the L-arginine–NO pathway in vascular smooth
muscle cells.
Key Words: muscle, smooth, vascular • relaxin • nitric oxide
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