argipressin--beta-mercapto-beta-beta-cyclopentamethylenepropionic-acid(1)-o-methyl-tyr(2)-val(4)- and Hemorrhage

The effect of separate and combined blockade of vasopressin (AVP) V1-receptors and angiotensin II formation on resistance to a slow venous haemorrhage (0.7 ml kg-1 min-1) was studied in six conscious adult sheep by bleeding to the point of an abrupt fall in the mean systemic arterial pressure (MSAP). Intravenous administration of the V1-receptor antagonist [d(CH2)5Tyr(Me)AVP] (10 micrograms kg-1) and/or the angiotensin I converting enzyme inhibitor captopril (20 mg + 1 mg h-1) did not cause any significant haemodynamic changes in the normovolaemic animal. The volume of haemorrhage necessary to induce acute hypotension (MSAP < 50 mmHg) was significantly smaller after AVP blockade alone (13.8 +/- 0.7 ml kg-1; P < 0.01) but not after captopril treatment (14.7 +/- 1.6 ml kg-1; n.s.) compared to control animals receiving no drug treatment (16.8 +/- 0.6 ml kg-1). The combined treatment with the AVP antagonist and captopril caused a further decrease in tolerance to haemorrhage (9.4 +/- 1.2 ml kg-1; P < 0.001). Blockade of AVP V1-receptors was associated with an attenuated increase in systemic vascular resistance immediately after the end of haemorrhage, concomitant with an accentuated lowering of the central venous pressure. In contrast, captopril treatment decreased the degree of vasoconstriction mainly during the second half of the posthaemorrhage observation period of 1 hour. It is concluded that both AVP and angiotensin II contribute to the maintenance of the MSAP during haemorrhage in conscious sheep.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Arginine Vasopressin; Blood Pressure; Captopril; Female; Hemorrhage; Receptors, Angiotensin; Receptors, Vasopressin; Sheep; Vascular Resistance; Vasoconstriction

In 8 chronically cannulated fetal lambs between 119 and 127 days gestation the resting plasma norepinephrine concentration was 528 +/- 77 pg X ml-1 and the resting plasma epinephrine concentration 159 +/- 42 pg X ml-1. Hemorrhage of 20% of estimated blood volume at 2% per min produced a 2.1-fold increase in plasma norepinephrine levels and a 3.4-fold increase in plasma epinephrine levels when the animals were pretreated with an injection of saline (1 ml). Plasma catecholamine levels returned toward control values following return of the shed blood. In contrast, hemorrhage of these animals following pretreatment with an antagonist of the pressor effect of vasopressin did not cause an increase in fetal plasma catecholamine levels. Thus, vasopressin may mediate the sympathetic responses to volume depletion in the fetus.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Epinephrine; Female; Fetal Diseases; Fetus; Hemorrhage; Norepinephrine; Pregnancy; Sheep; Vasopressins