Prostacyclin reduces "preload" in conscious dogs via a vagal reflex mechanism.
The purpose of this study was to determine the effects of prostacyclin on left ventricular (LV) preload in conscious dogs. LV end-diastolic diameter (LV EDD) was used as an index of preload. Because prostacyclin reduces arterial pressure, data were sampled when mean arterial pressure, heart rate, and first derivative of LV pressure (dP/dt) had returned to control levels. There was no dose-response relationship in the preload reduction to prostacyclin, the threshold dose being 0.1 microgram/kg. Intravenous prostacyclin (2.0 micrograms/kg) reduced LV EDD 2.9 +/- 0.5% from 36 +/- 2.2 mm, (P less than 0.01). With heart rate held constant (146 +/- 2.5 beats/min) by electrical pacing, prostacyclin still reduced LV EDD by 4.0 +/- 1.0% from 32 +/- 2.5 mm (P less than 0.05). Intravenous administration of arachidonic acid (500 micrograms/kg) gave similar results. The magnitude of the preload response to prostacyclin was similar to that of nitroglycerin (25 micrograms/kg). Prazosin (1 mg/kg) or bilateral cervical vagal section completely abolished the preload response to prostacyclin but not to nitroglycerin. We, therefore, propose a mechanism where prostacyclin activates cardiopulmonary receptors with vagal afferents that results in a withdrawal of peripheral sympathetic tone to capacitance vessels to reduce preload, in contrast to nitroglycerin, whose mechanism of action is most probably a direct effect on capacitance vessels.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008955:Models, Cardiovascular; D005996:Nitroglycerin / Q000494:pharmacology; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D001095:Arachidonic Acids; D016718:Arachidonic Acid; D011464:Epoprostenol; D005996:Nitroglycerin