The effect of urocortin II administration on the coronary circulation and cardiac function in the anaesthetized pig is nitric-oxide-dependent.
We planned to determine the primary effects and mechanisms of urocortin II, a member of the corticotrophin-releasing factor (CRF) family highly expressed in the cardiovascular system, on coronary blood flow and myocardial function in vivo. Urocortin II was infused into the left anterior descending coronary artery in 25 anaesthetized pigs whilst measuring haemodynamic variables, coronary blood flow, ventricular dP/dt(max) cardiac output and percentage of segmental shortening. This infusion was repeated after blockade of the autonomic nervous system, nitric-oxide synthase (NOS) or subtype 2 of the CRF receptors. In all experiments changes in heart rate and aortic blood pressure were prevented. Intra-coronary urocortin II increased, within 60 s, coronary blood flow (15+/-3.2%, P<0.05), dP/dt(max) (12.7+/-2.6%, P<0.05), cardiac output (16+/-2.3%, P<0.05) and percentage of segmental shortening (19.8+/-3.8%, P<0.05). Blockade of NOS abolished only the coronary effects whereas blockade of subtype 2 of the CRF receptors abolished all cardiac and coronary effects. It was shown for the first time that urocortin II administration primarily increases coronary blood flow and myocardial function through the release of nitric oxide and activation of subtype 2 of the CRF receptors in the anaesthetized pig. This provides a mechanism through which a local increase of urocortin II levels can help improve a compromised cardiovascular function.
Grossini
Elena
E
Laboratorio di Fisiologia, Dipartimento di Medicina Clinica e Sperimentale, Facoltà di Medicina e Chirurgia, Università del Piemonte Orientale A. Avogadro, via Solaroli 17, I-28100 Novara, Italy. grossini@med.unipmn.it
Molinari
Claudio
C
Mary
David A S G
DA
Marino
Paolo
P
Vacca
Giovanni
G
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000768:Anesthesia, General; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects; D002302:Cardiac Output; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000294:innervation; D007261:Infusions, Intra-Arterial; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012039:Regional Blood Flow; D034421:Sus scrofa; D054832:Urocortins / Q000008:administration & dosage / Q000378:metabolism*; D014664:Vasodilation; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; C101531:CRF receptor type 2; D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C116607:antisauvagine 30; D009569:Nitric Oxide; D001285:Atropine; D011433:Propranolol; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D010646:Phentolamine