Cardiovascular responses to vasoactive intestinal contractor, a novel endothelin-like peptide.
Cardiovascular and pulmonary responses to vasoactive intestinal contractor (VIC), an endothelin (ET)-like peptide from the murine gastrointestinal tract, were investigated in the cat. VIC (0.1-1.0 nmol/kg iv) decreased or elicited biphasic changes in arterial pressure (AP) and increased central venous pressure, cardiac output, pulmonary arterial pressure, and left atrial pressure. VIC produced biphasic changes in systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR). VIC increased heart rate (HR) and, at the 1 nmol/kg dose, a secondary decrease was observed. Hexamethonium blocked the changes in HR in response to VIC, whereas the ganglionic blocker, meclofenamate, or glybenclamide had no effect on changes in AP, SVR, and PVR elicited by the peptide. VIC caused small changes in right ventricular contractile force and increased distal aortic and carotid artery blood flow at all doses, with secondary decreases at the higher doses. VIC decreased superior mesenteric artery flow and decreased renal blood flow at the 1 nmol/kg dose. The changes in AP in response to VIC, ET-1, and ET-2 were similar, whereas those elicited by ET-3 and sarafotoxin 6b were similar. The present data show that VIC can produce both vasodilation and vasoconstriction in the systemic vascular bed and biphasic changes in PVR in the cat. These data show that VIC can produce complex cardiovascular responses similar to those elicited by the ET peptides and that these responses are largely independent of autonomic reflexes, release of cyclooxygenase products, and activation of ATP-regulated potassium channels. We conclude that VIC may act as an ET-like peptide.
Minkes
R K
RK
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Higuera
T R
TR
Rogers
G F
GF
Sheldon
E A
EA
Langston
M A
MA
Kadowitz
P J
PJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D002415:Cats; D002496:Central Venous Pressure / Q000187:drug effects; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D016232:Endothelins; D006584:Hexamethonium Compounds; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C059568:vasoactive intestinal constrictor; D018738:Hexamethonium; D008469:Meclofenamic Acid; D005905:Glyburide