David T. W. Fei

[DES-ASP1] angiotensin II in the sheep: Blood levels and its effect on plasma renin concentration

Abstract The present study describes an improved method for measuring angiotensin III in arterial blood. This was accomplished by SE-sephadex column to separate angiotensin II from angiotensin III prior to radioimmunoassay. The arterial concentration of angiotensin III measured before and after 24 to 48 hours sodium depletion by acute cannulation of parotid gland was 12.4 ± 1.7 fmol/ml (SEM, n=7) and 49.8 ± 10.3 fmol/ml (SEM, n=7) respectively. The arterial concentration of Val 4 -angiotensin III obtained from continuous infusion of Val 4 -angiotensin III at rates of 24 and 48 nmol/h in sodium deficient sheep were 245 ± 32.5 fmol/ml (n=6) and 330 ± 11.4 fmol/ ml (n=7) respectively. The clearance rate of exogenous Val 4 -angiotensin III in sodium deficient sheep after correction for endogenous level was calculated to be 140 ± 13.6 L/h (SEM, n=13). This was in the same order as Ile 5 -angiotensin II and Ile 4 -angiotensin III reported earlier in sodium replete sheep. Prolonged intravenous infusion of Val 4 -angiotensin III at a rate of 48 nmol/h in sodium- deficient sheep suppressed plasma renin concentration to the same extent as equimolar infusions of angiotensin II. This suggests that angiotensin III may inhibit renin secretion by a similar mechanism to angiotensin II.

INTRACEREBROVENTRICULAR INFUSIONS OF CORTICOTROPHIN RELEASING FACTOR (CRF) AND ACTH RAISE BLOOD PRESSURE IN SHEEP

1. Infusion of synthetic ovine CRF (10 or 100 μg/h) into the lateral cerebral ventricle for 24 h increased mean arterial blood pressure of conscious sheep.

Blood clearance rates of angiotensin II and its metabolites in sheep: presence of immunoreacttve fragments in arterial blood

1. The blood clearance rates of exogenous (des‐1‐Asp)‐angiotensin II and (des‐1‐Asp‐2‐Arg)‐angiotensin II calculated from the arterial blood level during steady state infusion in conscious sodium‐replete sheep were found to be 125 litre/h (s.d. = 27, n= 18) and 188 litre/h (s.d. = 23, n= 18), respectively. These blood clearance rates were in the same order as values for angiotensin II previously reported.

Reduction of blood clearance rate of [Val5] angiotensin II by [Sar1, ILE8] angiotensin II in sheep

Abstract The present study examines the effect of [Sar1, Ile8] angiotensin II ([Sar1, Ile8] ANG II) on the blood clearance rate of [Val5] angiotensin II ([Val5] ANG II) in conscious, sodium-replete sheep. Animals were infused simultaneously with [Val5] ANG II and [Sar1, Ile8] ANG II at a rate of 42 nmol/h and 6 μmol/h respectively. Blood [Val5] ANG II was quantitatively determined with care taken in separating [Val5] ANG II from [Sar1, Ile8] ANG II prior to radioimmunoassay. The blood clearance rate of [Val5] ANG II calculated from infusion rate/blood concentration was significantly different before and during [Sar1, Ile8] ANG II infusion, being 141 ± 13 L/h (n = 12) and 95 ± 10 L/h (n = 12) respectively. Plasma renin concentration remained suppressed after the commencement of [Sar1, Ile8] ANG II infusion. In-vitro studies showed no significant decrease in the rate of degradation of [Val5] ANG II in blood in the presence of [Sar1, Ile8] ANG II. Possible interpretation of this reduction of blood clearance rate of [Val5] ANG II by 45 ± 15 L/h (n = 6) was discussed.

Angiotensin converting enzyme inhibition does not prevent development of ACTH-induced hypertension in sheep.

1. The role of the renin‐angiotensin system in the onset of ACTH‐induced hypertension was examined in five conscious sheep.

Renal autotransplants in sheep: investigation of renal function and renovascular hypertension.

1. A novel surgical preparation of sheep with a cervical renal autotransplant has been developed.

Active and inactive renin in critically ill patients

1. The relationship between active (A) and inactive (I) plasma renin concentrations (PRC) was examined in critically ill patients to test for intravascular renin activation in states of shock and tissue damage.

The hemodynamic effects of prostacyclin infusions in normotensive and ACTH induced hypertensive conscious sheep

The aim of this study was to determine the effect of ACTH-induced hypertension on the hemodynamic dose-response curves to intravenous infusion of prostacyclin (PGI2) in conscious sheep. PGI2 was infused for 10 minutes at doses of 0.05-0.50 micrograms/kg per min and hemodynamic dose-response curves were performed before, during and after ACTH-induced hypertension. Prior to ACTH administration prostacyclin infusions produced dose dependent decreases in mean arterial pressure (MAP), calculated total peripheral resistance (CTPR) and stroke volume (SV). These changes were accompanied by an increase in cardiac rate (CR) and cardiac output (CO). After five days of ACTH treatment MAP had risen from 72 +/- 1 to 91 +/- 2 mm Hg and infusions of PGI2 produced similar effects on MAP to those seen prior to ACTH. However the effects on CTPR, CO, SV and CR were all potentiated relative to normotensive animals. Three days after ACTH administration had ceased and basal pressure had returned to normotensive levels, the responses of CR, CO and SV to PGI2 infusions were similar to those seen prior to ACTH. However the exaggerated fall in CTPR seen during ACTH treatment was still present and this resulted in a very large decrease in MAP. These studies suggest that in this model of steroid-induced hypertension the resistance vessels are more sensitive to PGI2 and that the blood pressure response to PGI2 is regulated by different mechanisms to those seen prior to ACTH.

EFFECT OF CONVERTING ENZYME INHIBITION WITH CAPTOPRIL ON IN VITRO ANGIOTENSIN PRODUCTION IN SHEEP

1. The effect of captopril on in vitro production of angiotensin I (ANG I), [Val5] ‐angiotensin II ([Vals]‐ANG II) and [Val4]‐angiotensin III ([Val5]‐ANG‐(2–8)) in central venous blood taken from sodium‐deficient sheep was studied.