title: Neurohumoral regulation of the pulmonary circulation during circulatory hypotension in conscious dogs.
abstract: We investigated the effects of circulatory hypotension (HYPO) on the left pulmonary vascular pressure-flow relationship in chronically instrumented conscious dogs and the role of five neurohumoral mechanisms in either mediating or modulating the response to this stimulus. HYPO was induced by acute (approximately 15-min) inflation of a hydraulic occluder implanted around the thoracic inferior vena cava, which decreased systemic arterial pressure to approximately 55 mmHg. HYPO resulted in active pulmonary vasoconstriction (53-66%; P < 0.01) in intact conscious dogs. Sympathetic alpha 1-adrenoreceptor block reduced (P < 0.01) the magnitude of HYPO-induced pulmonary vasoconstriction by 91-99%. Neither sympathetic beta-adrenoreceptor block nor cholinergic muscarinic receptor block had any significant effect on the magnitude of HYPO-induced pulmonary vasoconstriction. Surprisingly, angiotensin II receptor block increased (P < 0.05) HYPO-induced pulmonary vasoconstriction by 69-91%. In contrast, arginine vasopressin V1-receptor block reduced (P < 0.05) HYPO-induced pulmonary vasoconstriction by 34-41%. These results indicate that the pulmonary circulation of intact conscious dogs is actively regulated by three distinct neurohumoral mechanisms during HYPO. Sympathetic alpha 1-adrenoreceptor activation is the primary mediator of HYPO-induced pulmonary vasoconstriction. Angiotensin II and arginine vasopressin exert opposing pulmonary vasodilator and vasoconstrictor effects during HYPO, whereas sympathetic beta-adrenoreceptor and cholinergic muscarinic receptor activation do not appear to modulate the pulmonary vascular response to HYPO.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-4961.
authors.forename: W P
authors.initials: WP
authors.lastname: Peterson
authors.forename: G A
authors.initials: GA
authors.lastname: Trempy
authors.forename: K
authors.initials: K
authors.lastname: Nishiwaki
authors.forename: D P
authors.initials: DP
authors.lastname: Nyhan
authors.forename: P A
authors.initials: PA
authors.lastname: Murray
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D004285:Dogs; D007022:Hypotension / Q000503:physiopathology*; D008297:Male; D018727:Muscarinic Antagonists; D018377:Neurotransmitter Agents / Q000502:physiology*; D010276:Parasympatholytics / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D018727:Muscarinic Antagonists; D018377:Neurotransmitter Agents; D010276:Parasympatholytics; D018340:Receptors, Adrenergic, alpha-1; D011945:Receptors, Angiotensin; D011976:Receptors, Muscarinic; D017483:Receptors, Vasopressin; D000804:Angiotensin II; D001127:Arginine Vasopressin