-transparent.png){kind=logo}
BACKGROUND Plasma levels of adrenomedullin are increased in patients with congestive heart failure, but there has been no report concerning the effects of adrenomedullin on the heart. We investigated the effects of adrenomedullin on NO synthase activity in cardiac myocytes. RESULTS We measured the production of nitrite, a stable metabolite of NO, in cultured neonatal rat cardiac myocytes with the Griess reagent. Inducible NO synthase mRNA and protein expression were assayed by Northern and Western blotting, respectively. Incubation of the cultures with interleukin-1 beta (10 ng/mL) for 24 hours caused a significant increase in nitrite accumulation. Adrenomedullin significantly augmented nitrite production by interleukin-1 beta-stimulated but not by unstimulated cardiac myocytes in a dose-dependent manner (10(-10) to 10(-6) mol/L). The adrenomedullin-induced nitrite production by interleukin-1 beta-stimulated cells was accompanied by increased inducible NO synthase mRNA and protein expression. In the presence of dibutyryl cAMP, the interleukin-1 beta-induced nitrite accumulation was increased further, but the stimulatory effect of adrenomedullin on nitrite production was abolished. Adrenomedullin dose-dependently increased intracellular cAMP levels in cardiac myocytes. Addition of the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP[8-37] to the culture dose-dependently inhibited both cAMP and NO generation stimulated by adrenomedullin. CONCLUSIONS These results indicate that adrenomedullin acts on cardiac myocytes and augments NO synthesis in these cells under cytokine-stimulated conditions, at least partially through a cAMP-dependent pathway.
U Ikeda, and
T Kanbe, and
Y Kawahara, and
M Yokoyama, and
K Shimada
October 2002,
Cardiovascular research,
U Ikeda, and
T Kanbe, and
Y Kawahara, and
M Yokoyama, and
K Shimada
July 2001,
Journal of cardiovascular pharmacology,
U Ikeda, and
T Kanbe, and
Y Kawahara, and
M Yokoyama, and
K Shimada
November 1995,
Circulation,
U Ikeda, and
T Kanbe, and
Y Kawahara, and
M Yokoyama, and
K Shimada
April 1996,
Journal of molecular and cellular cardiology,
U Ikeda, and
T Kanbe, and
Y Kawahara, and
M Yokoyama, and
K Shimada
January 1998,
The American journal of physiology,
U Ikeda, and
T Kanbe, and
Y Kawahara, and
M Yokoyama, and
K Shimada
May 1998,
The Journal of biological chemistry,
U Ikeda, and
T Kanbe, and
Y Kawahara, and
M Yokoyama, and
K Shimada
September 1997,
Circulation,
U Ikeda, and
T Kanbe, and
Y Kawahara, and
M Yokoyama, and
K Shimada
October 1999,
Cardiovascular research,
U Ikeda, and
T Kanbe, and
Y Kawahara, and
M Yokoyama, and
K Shimada
March 2004,
Biochemical pharmacology,
U Ikeda, and
T Kanbe, and
Y Kawahara, and
M Yokoyama, and
K Shimada
December 2000,
Hypertension (Dallas, Tex. : 1979),
