Analysis of cardiovascular and pulmonary responses to endothelin-1 and endothelin-3 in the anesthetized cat.
Cardiovascular and pulmonary responses to endothelin (ET)-1, ET-3 and neuropeptide Y (NPY) were investigated in the anesthetized cat. ET-1, 0.1 to 1 nmol/kg i.v., decreased or elicited biphasic changes in arterial pressure (AP), whereas ET-3, in the same doses, decreased AP. Both ETs increased cardiac output (CO) and, at the highest doses, a secondary decrease in CO was observed. NPY, 0.3 to 3 nmol/kg i.v., increased AP and at the highest dose decreased CO. All three peptides had inconsistent effects on right ventricular contractile force and increased central venous pressure. ET-1 at lower doses increased heart rate (HR) and, at 1 nmol/kg, caused a biphasic change. ET-3 increased HR, whereas NPY decreased HR. Systemic vascular resistance (SVR) was increased by NPY and decreased by ET-3, whereas ET-1 elicited biphasic changes. ET-1 and ET-3 increased pulmonary arterial pressure, left atrial pressure and caused biphasic changes in pulmonary vascular resistance (PVR). NPY had no significant effect on PAP or PVR. When pulmonary blood flow was maintained constant, ET-1 and ET-3 had only pulmonary vasoconstrictor activity, whereas NPY and the ET analog had no significant effect. The increase in SVR in response to NPY, the decrease in response to ET-3 or the biphasic change in response to ET-1 were not modified by meclofenamate, hexamethonium or propranolol. Increases in HR in response to ET-1 and ET-3 were reduced by the beta receptor and ganglionic blocking agents.(ABSTRACT TRUNCATED AT 250 WORDS)
Minkes
R K
RK
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
Bellan
J A
JA
Saroyan
R M
RM
Kerstein
M D
MD
Coy
D H
DH
Murphy
W A
WA
Nossaman
B D
BD
McNamara
D B
DB
Kadowitz
P J
PJ
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002415:Cats; D004305:Dose-Response Relationship, Drug; D016232:Endothelins; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D018738:Hexamethonium; D006584:Hexamethonium Compounds; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects*; D008469:Meclofenamic Acid / Q000494:pharmacology; D009478:Neuropeptide Y / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology
D000959:Antihypertensive Agents; D016232:Endothelins; D006584:Hexamethonium Compounds; D009478:Neuropeptide Y; D010455:Peptides; D018738:Hexamethonium; D008469:Meclofenamic Acid; D011433:Propranolol