The spleen is required for 5-HT1A receptor agonist-mediated increases in mean circulatory filling pressure during hemorrhagic shock in the rat.
The 5-HT(1A) receptor agonist, 8- OH-DPAT, increases whole body venous tone (mean circulatory filling pressure; MCFP), and attenuates metabolic acidosis in a rat model of unresuscitated hemorrhagic shock. To determine whether improved acid-base balance was associated with sympathetic activation and venous constriction, MCFP, sympathetic activity (SA), and blood gases were compared in hemorrhaged rats following administration of 5-HT(1A) receptor agonist 8-OH-DPAT, the arterial vasoconstrictor arginine vasopressin (AVP), or saline. To further determine whether protection of acid-base balance was dependent on splenic contraction and blood mobilization, central venous pressure (CVP), MCFP, and blood gases were determined during hemorrhage and subsequent 8-OH-DPAT-administration in rats subjected to real or sham splenectomy. Subjects were hemorrhaged to an arterial pressure of 50 mmHg for 25 min and subsequently were treated with 8-OH-DPAT (30 nmol/kg iv), AVP titrated to match the pressor effect of 8-OH-DPAT (approximately 2 ng/min iv), or infusion of normal saline. 8-OH-DPAT increased MAP, CVP, MCFP, and SA, and decreased lactate accumulation. AVP did not affect CVP or SA, but raised MCFP slightly to a level intermediate between 8-OH-DPAT- and saline-treated rats. Infusion of AVP also produced a modest protection against metabolic acidosis. Splenectomy prevented the rise in CVP, MCFP, and protection against metabolic acidosis produced by 8-OH-DPAT but had no effect on the immediate pressor response to the drug. Together, the data indicate that 8-OH-DPAT produces a pattern of cardiovascular responses consistent with a sympathetic-mediated venoconstriction that is, in part, responsible for the drug's beneficial effect on acid-base balance. Moreover, blood mobilization stimulated by the spleen is required for the beneficial effects of 8-OH-DPAT.
Tiniakov
Ruslan
R
Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA.
Scrogin
Karie E
KE
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001775:Blood Circulation / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D058825:Serotonin 5-HT1 Receptor Agonists; D018490:Serotonin Agents / Q000494:pharmacology; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D013154:Spleen / Q000502:physiology*; D013156:Splenectomy; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D058825:Serotonin 5-HT1 Receptor Agonists; D018490:Serotonin Agents; D014662:Vasoconstrictor Agents; D044282:Receptor, Serotonin, 5-HT1A; D001127:Arginine Vasopressin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin