The 5-hydroxytryptamine1A receptor agonist, (+)-8-hydroxy-2-(di-n-propylamino)-tetralin, increases cardiac output and renal perfusion in rats subjected to hypovolemic shock.
The 5-hydroxytryptamine(1A) receptor agonist, (+)-8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), raises blood pressure (BP) and venous tone in rats subjected to hemorrhagic shock. Here, BP, ascending aortic blood flow [i.e., estimate of cardiac output (CO)] and venous blood gases were measured to determine the hemodynamic effects of 8-OH-DPAT (30 nmol/kg i.v., n = 10), saline (n = 10), or an equipressor infusion of epinephrine (n = 10) in unanesthetized rats subjected to hemorrhagic shock (25 min of hypotensive hemorrhage, approximately 50 mm Hg). Renal and iliac blood flow were measured in separate groups of similarly hemorrhaged rats given the same dose of 8-OH-DPAT (n = 7) or saline (n = 6). Compared with saline treatment, 8-OH-DPAT produced a sustained rise in BP (+32 +/- 4 versus +9 +/- 2 mm Hg, 15 min after injection, P < 0.01) and CO (+27 +/- 5 versus +4 +/- 6 ml/min/kg, P < 0.01) but did not affect total peripheral resistance (TPR). Infusion of epinephrine reduced CO (-12 +/- 6 ml/min/kg, P < 0.01) and dramatically increased TPR [+0.37 +/- 0.11 versus +0.05 +/- 0.05 log (mm Hg/ml/min/kg), P < 0.01]. 8-OH-DPAT increased renal conductance (+7 +/- 1 versus +4 +/- 1 microl/min/mm Hg, P < 0.01) but did not significantly affect iliac conductance. 8-OH-DPAT attenuated further development of acidosis compared with either saline or epinephrine (-5.6 +/- 1.6 versus -13.0 +/- 2.0 versus -11.3 +/- 2.6 mmol/liter base excess 45 min after start of hemorrhage, both P < 0.01 versus 8-OH-DPAT). These data demonstrate that 8-OH-DPAT improves hemodynamics during circulatory shock, in part, through renal vasodilation and mobilizing of blood stores.
Tiniakov
Ruslan
R
Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, IL, USA
Osei-Owusu
Patrick
P
Scrogin
Karie E
KE
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects*; D004837:Epinephrine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007085:Ilium / Q000098:blood supply / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012769:Shock / Q000503:physiopathology*
D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D002245:Carbon Dioxide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D009638:Norepinephrine; D004837:Epinephrine