Vasoactive intestinal peptide has a direct positive inotropic effect on isolated human myocardial trabeculae.
The aim of the present study was to assess the inotropic effects of vasoactive intestinal peptide (VIP) on isolated myocardial trabeculae from the right atrium and the left ventricle of human hearts. Furthermore, using reverse transcriptase-PCR, we wanted to determine the presence of mRNAs encoding the three cloned human VIP receptors, VPAC(1), VPAC(2) and PAC(1). The trabeculae were paced at 1.0 Hz in tissue baths, and changes in isometric contractile force upon exposure to agonist were studied. VIP had a potent positive inotropic effect in some of the atrial and ventricular trabeculae tested. This effect was almost completely blocked by the VIP-receptor antagonist VIP-(6-28). mRNAs encoding the human VPAC(1), VPAC(2) and PAC(1) receptors were detected in human myocardial trabeculae from both the right atrium and the left ventricle. In conclusion, VIP has a direct positive inotropic effect in both the atria and the ventricles of the human heart. The presence of mRNAs for the VPAC(1), VPAC(2) and PAC(1) receptors suggest that VIP may mediate its effect via these receptors.
Saetrum Opgaard
O
O
Department of Pharmacology, Erasmus University, 3000 DR Rotterdam, The Netherlands. osaetrum@uci.edu
Knutsson
M
M
de Vries
R
R
Tom
B
B
Saxena
P R
PR
Edvinsson
L
L
D000293:Adolescent; D000328:Adult; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D002316:Cardiotonic Agents; D010446:Peptide Fragments; D012333:RNA, Messenger; D018005:Receptors, Vasoactive Intestinal Peptide; C113198:vasoactive intestinal peptide (6-28); D014660:Vasoactive Intestinal Peptide