Cardiac and regional haemodynamic effects of endothelin-1 in rats subjected to critical haemorrhagic hypotension.
In the present study, we examined cardiac and regional haemodynamic effects of endothelin-1 (ET-1), a potent vasoconstrictive factor, in a rat model of pressure-controlled irreversible haemorrhagic shock resulting in the death of all control animals within 30 min. Experiments were carried out in male ethylurethane-anaesthetised Wistar rats subjected to hypotension of 20-25 mmHg, which resulted in bradycardia, an extreme decrease in cardiac index (CI) and an increase in total peripheral resistance index (TPRI), with reductions in renal (RBF), hindquarters (HBF) and mesenteric blood flow (MBF). ET-1 (50, 200 pmol/kg) administered intravenously at 5 min of critical hypotension produced increases in mean arterial pressure (MAP) and heart rate (HR), which were significantly higher than those in normotensive animals, and a 100% survival at 2 h after treatment. The effects were accompanied by a rise in CI, a decrease in TPRI, with increases in RBF and HBF and persistently lowered MBF, and an increase in circulating blood volume 20 min after treatment. The cardiovascular effects of ET-1 were inhibited by the ETA receptor antagonist BQ-123 (1 mg/kg), while the ETB receptor antagonist BQ-788 (3 mg/kg) had no effect. In conclusion, ET-1 acting via ETA receptors produces reversal of haemorrhagic hypotension in rats due to the mobilisation of blood from venous reservoirs, with the improvements in cardiac function and the perfusion of peripheral tissues.
Jochem
J
J
Department of Physiology, Medical University of Silesia, Zabrze, Poland.
Zwirska-Korczala
K
K
Gwóźdź
B
B
Walichiewicz
P
P
Jośko
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001919:Bradycardia / Q000150:complications / Q000188:drug therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006470:Hemorrhage / Q000150:complications; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects; D007022:Hypotension / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology*; D007275:Injections, Intravenous; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000493:pharmacokinetics; D010880:Piperidines / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000008:administration & dosage / Q000627:therapeutic use; D012079:Renal Circulation / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology*; D012965:Sodium Chloride / Q000008:administration & dosage; D013152:Splanchnic Circulation / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; C086539:BQ 788; D012965:Sodium Chloride; C072247:cyclo(Trp-Asp-Pro-Val-Leu)