Profile of circulating vasoactive substances in hemorrhagic shock and their pharmacologic manipulation.
(a) Hemorrhage in dogs (to 45-50 mm Hg) was associated with a 10-fold increase in plasma renin activity (PRA) which remained elevated throughout the time-course of shock including the irreversible (decompensation) stage. The presence of angiotensin II (AII) in arterial blood was demonstrated by the bloodbathed organ technique and confirmed by blockade with specific AII antagonists (cysteine(8)-AII or isoleucine(8)-AII). The contribution of AII to systemic peripheral resistance during hemorrhage shock in dogs was established by administering AII antagonists which immediately cause a further fall in blood pressure.(b) Plasma catecholamines (CA) steadily increased during hemorrhage and peaked during compensation (a 100-fold increase). The CA decreased progressively during decompensation.(c) Prostaglandin (PG) E-like material was observed in arterial blood for 15-60 min (after hemorrhage); the peak arterial concentration was 2.6 ng/ml blood. Indomethacin (i.v., before 80% of maximum bleedout): (i) confirmed the presence of PGE, (ii) increased blood pressure, and (iii) increased blood loss.(d) Thus: peripheral resistance during hemorrhagic shock seems temporally correlated with blood CA levels (and not PRA), and the renin-AII system contributes to the maintenance of vascular resistance and may markedly decrease perfusion of organs, such as kidney; the administration of the proper combination of specific antagonists of vasoconstrictor humoral substances may radically improve organ perfusion and could contribute to ultimate recovery from hemorrhagic shock.
D000804:Angiotensin II / Q000097:blood* / Q000502:physiology; D000818:Animals; D001794:Blood Pressure; D002339:Carotid Arteries; D002395:Catecholamines / Q000097:blood*; D004285:Dogs; D006439:Hemodynamics; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D010643:Phenoxybenzamine / Q000494:pharmacology; D011453:Prostaglandins / Q000097:blood; D011863:Radioimmunoassay; D012083:Renin / Q000097:blood*; D012771:Shock, Hemorrhagic / Q000097:blood* / Q000503:physiopathology; D014655:Vascular Resistance; D014666:Vasomotor System
D002395:Catecholamines; D011453:Prostaglandins; D010643:Phenoxybenzamine; D000804:Angiotensin II; D012083:Renin; D007213:Indomethacin