Relaxin increases rat heart rate by a direct action on the cardiac atrium.
Relaxin (Rlx) is best understood as a protein hormone of pregnancy that can influence pelvic and cervical connective tissue as well as uterine smooth muscle activity. Thus, it was unexpected that dense Rlx binding sites would be found in the rat cardiac atrium. To functionally characterize this finding, isolated rat atria were challenged with Rlx (0.3 to 30 ng/ml), and they responded with an increased rate (+36%) and force (+38%) of contraction Further studies in conscious normotensive and spontaneously hypertensive rats established by minipump circulating Rlx levels of about 0.5 and 5 ng/ml over 1 to 2 wks. There were significant increases in heart rate of 10-15%, with no consistent changes in blood or urine volume, water or food intake, and mean arterial pressure. We conclude that Rlx can directly stimulate rat cardiac atrial activity in vitro and cause chronotropy in vivo.
Ward
D G
DG
Endocrine Research Department Genentech, Inc., South San Francisco, California 94080.
Thomas
G R
GR
Cronin
M J
MJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005813:Genes, Synthetic; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D012065:Relaxin / Q000235:genetics / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000187:drug effects
D011994:Recombinant Proteins; D012065:Relaxin