vasopressin--1-(1-mercaptocyclohexaneacetic-acid)-2-(o--methyl-l-tyrosine)-8-l-arginine- and Shock--Septic

We have demonstrated decreased microvascular sensitivity to norepinephrine during endotoxin shock possibly related to reduced sympathetic receptor activity (Baker et al.: Circ Shock 12:165-176, 1984). The response to other vascular controls such as arginine vasopressin (AVP) may also be altered. Reactivity of the left cremaster muscle microvessels of pentobarbital anesthetized Wistar rats was studied using videomicroscopy and videodensitometry. Femoral arterial pressure (Pm), dose response curves of vessel diameters to topical arginine vasopressin (10(-15) to 10(-6) M), FITC-albumin mean transit times, and plasma velocities were obtained. Escherichia coli endotoxin (6 mg/kg i.v., LD100) was infused over a 1-hr period. Parameter measurements were repeated at 30 min and 90 min post-endotoxin. Both Pm and plasma velocities progressively decreased. Arteriolar constriction and the mean transit times of FITC-labeled albumin progressively increased. The threshold dose for AVP averaged 10(-9) M at control and decreased to 10(-14) M post-endotoxin. Venular diameters were not altered by AVP. The AVP antagonist did not alter the microvascular diameter response to endotoxin but did block the responses to topical and endogenous AVP since arterial pressure and flow velocity decreased at a significantly greater rate than in rats without antagonist. Plasma AVP levels were significantly increased by endotoxin. Reduced alpha adrenergic sensitivity may unmask the responsiveness to AVP or increase the sensitivity of AVP receptors. Increased endogenous AVP may require a smaller exogenous concentration of AVP for constriction.

Topics: Animals; Arginine Vasopressin; Blood Flow Velocity; Blood Pressure; Endotoxins; Escherichia coli; Male; Microcirculation; Rats; Rats, Inbred Strains; Shock, Septic; Vasoconstriction

Chemical antagonists were used to assess the role of beta-endorphin and arginine-vasopressin (AVP) in canine endotoxin shock. Fifteen awake dogs were given Escherichia coli endotoxin IV. Within 5 min, CO decreased to 28%, LV dP/dt to 46%, and MAP to 52% baseline. Fifteen minutes after endotoxin, five dogs each received naloxone, AVP antagonist, or no treatment. Control (untreated) animals exhibited persistent cardiovascular depression, with CO 49%, LV dP/dt 69%, and MAP 91% of baseline after 45 min. Naloxone improved CO to 69%, LV dP/dt to 94%, and MAP to 91% by 30 min after treatment. AVP blockade improved CO to 105%, LV dP/dt to 107%, and MAP to 95% of baseline by 30 min after treatment, and caused significant tachycardia. Plasma cortisol and AVP increased markedly in all groups after endotoxin administration. AVP antagonist treatment increased mean survival from 1.4 to 4 days. These data suggest that abnormally elevated AVP contributes to cardiovascular depression in canine endotoxin shock and that AVP blockade is therapeutic in the animal model studied.

Topics: Animals; Arginine Vasopressin; beta-Endorphin; Blood Pressure; Cardiac Output; Cardiovascular Diseases; Dogs; Endorphins; Endotoxins; Escherichia coli; Female; Heart Rate; Hydrocortisone; Kinetics; Male; Naloxone; Shock, Septic

The role of the sympathetic nervous system, angiotensin II (ANG II), and arginine vasopressin (AVP) in maintaining blood pressure (BP) during endotoxic shock was investigated in 117 conscious male Wistar rats. After intravenous injection of 2 mg Escherichia coli endotoxin, mean BP fell within 5 min by approximately 50 mmHg and rose again to approach base-line levels within 90 min. At that time, plasma renin activity, plasma norepinephrine (NE), and vasopressin levels of the endotoxin-treated animals were, respectively, 12-, 10-, and 54-fold (P less than 0.001) higher than those of the controls. The BP effect of either prazosin (0.125 mg iv), captopril (2.5 mg iv), or d(CH2)5Tyr(Me)AVP (5 micrograms iv), a specific antagonist of the vascular effect of AVP, was evaluated over a 30-min observation period starting 90 min after administration of endotoxin or its vehicle. Captopril reduced mean BP from 116 +/- 1.8 to a low of 109 +/- 2.1 (SE) mmHg (P less than 0.05, n = 8) only in rats pretreated with endotoxin, whereas the vasopressin antagonist had no depressor effect even during endotoxemia. The BP drop induced by prazosin in rats exposed to endotoxin (-21 +/- 3.3 mmHg, n = 6) did not significantly differ from that observed in control rats (-14 +/- 3.4 mmHg, n = 6). A dose-response curve to NE, ANG II, and lysine vasopressin was also performed. In endotoxin-treated rats the mean BP response to all agonists was markedly suppressed (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin II; Animals; Arginine Vasopressin; Blood Pressure; Captopril; Endotoxins; Epinephrine; Male; Norepinephrine; Pentobarbital; Prazosin; Rats; Rats, Inbred Strains; Renin; Shock, Septic; Sympathetic Nervous System; Vasopressins