angiotensin-i and Shock--Septic

Classic and nonclassic renin-angiotensin systems (RAS) are 2 sides of an ubiquitous endocrine/paracrine cascade regulating blood pressure and homeostasis. Angiotensin II and angiotensin-converting enzyme (ACE) levels are associated with severity of disease in the critically ill, and are central to the physiology and the pathogenesis of circulatory shock. Angiotensin (1-7) and ACE2 act as an endogenous counterregulatory arm to the angiotensin II/ACE axis. The tissue-based RAS has paracrine effects dissociated from those of the circulating RAS. Exogenous angiotensin II or ACE2 may improve the outcome of septic shock and acute respiratory distress syndrome, respectively.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Angiotensin I; Angiotensin II; Blood Pressure; Critical Illness; Female; Homeostasis; Humans; Male; Middle Aged; Peptide Fragments; Renin-Angiotensin System; Respiratory Distress Syndrome; Shock, Septic; Vasoconstrictor Agents

The pressor and intra-renal actions and effects of octa - and deca-peptides angiotensins II and I and of the catecholamine noradrenaline, in anaesthetized and conscious sheep, are considered. The halothane anaesthetic substantially lowers pressor sensitivity to both peptides but does not influence their ability to liberate K(+) ions into the circulating plasma. In comparison with angiotensin II, both angiotensin I and noradrenaline -- with direct presentation to the kidney -- are ineffective in decreasing intra-renal blood flow. However, with left ventricular injection, both pressor compounds immediately increase the blood pressure, as does angiotensin II. Combined doses of the decapeptide and catecholamine are thus highly effective in raising the blood pressure while having a minimal effect on blood flow through the kidney. This overall situation could provide a basis for treating clinical shock, especially regarding septicaemia and septic shock. The lowered hind-limb blood flow, with administration of the pressor compounds into the femoral artery, contrasts strongly with the raised flow resulting from intravenous injection. Experimental procedures to establish, or otherwise, relevant hypothetical situations are detailed.

Topics: Angiotensin I; Angiotensin II; Animals; Electrolytes; Halothane; Kidney; Norepinephrine; Sepsis; Sheep; Shock, Septic

he intermediate and latter stages of canine endotoxin shock are characterized by a progressive decrease in cardiac output, increase in total peripheral resistance, and hypoglycemia. We have hypothesized that the renin-angiotensin system and glucagon may mediate the loss of cardiovascular and glucose homeostasis. E. Coli endotoxin shock (1 mg/kg; 055:B5) was induced in three groups of dogs and systemic hemodynamics, angiotensin I activity, and glucagon were monitored for 5 hr; endotoxin shock (n = 13); endotoxin shock + prior immunization with J5 mutant of E coli 0111 (n = 5); Endotoxin + captopril (20 micrograms/kg/hr; n = 9); and sham-operated time-matched controls (n = 8). Thirty minutes postshock, angiotensin I and glucagon began to increase. Angiotensin I activity reached a peak at 60 min postendotoxin (90 +/- 25 vs 5 +/- ng/ml/hr; p less than 0.001) and plateaued. Increased glucagon levels plateaued at 3.5 hr postshock (1500 +/- 200 vs 155 +/- 77 pg/ml; p less than 0.001). Cardiac output began to progressively decrease, total peripheral resistance began to increase, and persistent hypoglycemia developed at 3 hr postshock. Captopril inhibited the increase in total peripheral resistance and had no effect on the decrease in cardiac output or the hypoglycemia. The initial glucagon response was attenuated but there was no difference at 5 hr (950 +/- 150 vs 1200 +/- 200 pg/ml). Prior immunization significantly preserved cardiac output, total peripheral resistance, plasma glucose levels, glucagon levels, and angiotensin I activity. It is concluded that 1) the renin-angiotensin system is a physiologic and not a pathophysiologic compensatory mechanism during the course of endotoxin shock and that inhibition of this system is deleterious; 2) glucagon may serve as an important mediator of both the myocardial dysfunction and glucose dyshomeostasis of endotoxin shock; and 3) immunological inhibition of the initial phase of endotoxin shock significantly preserves cardiovascular and glucose homeostasis and adds support to the concept that the initial vascular phase of endotoxin shock plays a primary role in determining the severity of the endotoxin/septic shock syndrome.

Topics: Angiotensin I; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animals; Blood Glucose; Blood Pressure; Captopril; Cardiac Output; Dogs; Endotoxins; Escherichia coli; Female; Glucagon; Hemodynamics; Male; Proline; Renin; Renin-Angiotensin System; Shock, Septic; Vascular Resistance