Salusins promote cardiomyocyte growth but does not affect cardiac function in rats.
Salusin-alpha and -beta are newly found polypeptides that stimulate proliferation, hypotension and bradycardia in vascular smooth muscle cells (VSMCs) and fibroblasts. Propresalusin mRNA is widespread, and positive stains for salusins have been observed in many human tissues such as endothelium and ventricular tissue. To investigate the bio-effect of salusins on cardiovascular function, 20 nmol/kg salusin-alpha or 2 nmol/kg salusin-beta was intravenously (i.v.) injected into rats, and isolated rat hearts were perfused with 10(-12) to 10(-7) mol/l salusin-alpha or -beta. (45)Ca(2+) uptake and (3)H-Leucine incorporation were determined in cultured neonatal rat cardiomyocytes. Neither salusin-a nor -beta affected cardiac function in vivo or in vitro but salusin-beta decreased mean arterial blood pressure (MAP). The polypeptides' stimulation of (45)Ca(2+) uptake and (3)H-Leucine incorporation was concentration-dependent, and the incorporation was inhibited by nicardipine (Nic) and FK-506 [FK; an inhibitor of calcineurin (CaN)]. PD(98059) [PD; inhibitor of mitogen-activated protein kinase (MAPK)] and chelerythrine [inhibitor of protein kinase C (PKC)] inhibited salusin-stimulated (3)H-Leucine incorporation. Endothelin-1 (ET) synergistically increased salusin-induced (45)Ca(2+) uptake. Our results suggest that salusin-alpha and -beta did not directly affect cardiac function in the rat heart but that they improved calcium uptake and protein synthesis in neonatal rat cardiomyocytes through the calcium, calcineurin, MAPK and PKC signal pathways. Salusins may be regulatory factors for myocardial growth and hypertrophy.
Yu
Fang
F
Department of Physiology, Health Science Center, Peking University, Beijing 100083, PR China.
Zhao
Jing
J
Yang
Jinghui
J
Gen
Bin
B
Wang
Shuheng
S
Feng
Xinheng
X
Tang
Chaoshu
C
Chang
Lin
L
D000251:Adenosine Triphosphatases / Q000008:administration & dosage*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004452:Echocardiography; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008934:Mitogens / Q000008:administration & dosage*; D032383:Myocytes, Cardiac / Q000502:physiology*; D010455:Peptides / Q000008:administration & dosage*; D010477:Perfusion; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000959:Antihypertensive Agents; D036341:Intercellular Signaling Peptides and Proteins; D008934:Mitogens; D010455:Peptides; C478739:TOR2A protein, human; D000251:Adenosine Triphosphatases; D002118:Calcium