Human RFamide-related peptide-1 diminishes cellular and integrated cardiac contractile performance.

Peptides influence cardiac dysfunction; however, peptidergic modulation of contractile performance remains relatively uncharacterized. We identified a novel human peptide that modulates mammalian contractile performance. Members of the FMRFamide-related peptide (FaRP) family contain a C-terminal RFamide but structurally variant N-terminal extension. We report human RFamide-related peptide-1 (hRFRP-1) and rat RFRP-1 rapidly and reversibly decreased shortening and relaxation in isolated mammalian cardiac myocytes in a dose dependent manner. The mammalian FaRP, 26RFa, structurally related to RFRP-1 by only an RFamide did not influence myocyte contractile function. The protein kinase C (PKC) inhibitor bisindolylmaleimide-1 blocked hRFRP-1 activity. Pretreatment with pertussis toxin (PTX) did not diminish hRFRP-1 influence on contractile function. In addition, intravenous injection of hRFRP-1 in mice decreased heart rate, stroke volume, ejection fraction, and cardiac output. Collectively these findings are consistent with the conclusion RFRP-1 is an endogenous signaling molecule that activates PKC and acts through a PTX-insensitive pathway to modulate cardiac contractile function. Taken together these negative chronotropic, inotropic, and lusitropic effects of hRFRP-1 are significant; they suggest direct acute cellular and organ-level responses in mammalian heart. This is the first known study to identify a mammalian FaRP with cardio-depressant effects, opening a new area of research on peptidergic modulation of contractile performance. The high degree of RFRP structure conservation from amphibians to mammals, and similarity to invertebrate cardioinhibitory peptides suggests RFRP-1 is involved in important physiological functions. Elucidation of mechanisms involved in hRFRP-1 synthesis, release, and signaling may aid the development of strategies to prevent or attenuate cardiac dysfunction.

Encouraging results. We will certainly continue to use the same basic strategy of national execution and program approach, aiming at sustainable output and process.

PIP: The UN Population Fund (UNFPA) has supported the government of Vietnam's population and family planning efforts since 1978. This support has produced encouraging results over the period. International experience has shown that government commitment is a key factor for the success of population programs. The government of Vietnam is very committed to population issues. For example, since 1992, a minister of population has been nominated, the National Committee for Population and Family Planning (NCPFP) has been strengthened, and the national budget allocated to the population sector has increased by almost ten-fold. This strong national-level commitment is also often seen at the local level. The author notes that UNFPA is no longer the only major international donor to Vietnam for population programs and highlights some recent population-related achievements in the country to which UNFPA contributed in recent years.^ieng