Capsaicin prevents the adrenocorticotropin-induced improvement of cardiovascular function and survival in hemorrhage-shocked rats.
A volume-controlled hemorrhagic shock was produced in anesthetized rats by intermittent bleeding from an iliac vein over a period of 20-30 min, until the carotid mean arterial pressure (MAP) stabilized around 20-24 mmHg. In this condition, which caused the death of all saline-treated animals within 25-30 min, the intravenous (i.v.) bolus injection of the adrenocorticotropin fragment 1-24 (ACTH(1-24)) at a dose of 160 micrograms/kg promptly restored MAP, as well as pulse pressure, heart rate and respiratory function, and greatly prolonged the survival time. Capsaicin (125 mg/kg cumulatively, s.c., 1 week before) completely prevented the anti-shock effect of ACTH(1-24), which, on the other hand, was shared by i.v. [Nle11]-substance P (SP) (200-300 micrograms/kg). Finally the SP-antagonist [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP prevented the effect of ACTH(1-24). These results suggest that SP-containing nerve fibers are required for the effect of ACTH in hemorrhagic shock.
D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology* / Q000633:toxicity; D003366:Cosyntropin / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D004723:Endorphins / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D012771:Shock, Hemorrhagic / Q000188:drug therapy / Q000503:physiopathology*; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D015996:Survival Rate
D004723:Endorphins; D011994:Recombinant Proteins; D003366:Cosyntropin; D013373:Substance P; C050702:substance P, Arg(1)-Pro(2)-Trp(7,9)-Leu(11)-; D000324:Adrenocorticotropic Hormone; D002211:Capsaicin