R. T. Mason

Effect of Angiotensin Converting Enzyme Inhibition with SQ 14 225 on Blood Pressure in Sheep

The effect of intravenous injection of the angiotensin converting enzyme inhibitor SQ 14 225 on blood pressure, heart rate and plasma renin concentration (PRC) was investigated in 15 intact conscious ewes as follows: sodium replete during angiotensin I infusion (n = 4); sodium replete (n = 6); sodium deplete (n = 5); chronic water deprivation (n = 5); AcTH treated sodium replete (n = 6). Following SQ 14 225 mean arterial pressure fell 5 +/- 1 mmHg in sodium replete, 20 +/- 4 mmHg in acutely sodium deplete, 7 +/- 2 mmHg in chronic water deprivation and 6 +/- 2 mmHg in ACTH treated sodium replete sheep. This suggests that the renin-angiotensin system plays no significant role in maintaining the elevated blood pressure of sheep with ACTH induced hypertension. Heart rate rose in all groups except the water deprived animals following SQ 14 225. PRC rose from 5.1 +/- 2.1 pmo1AI/ml plasma/h. to 12.4 +/- 2.0 in sodium replete sheep, from 11.9 +/- 1.0 to 68 +/- 13 in acutely sodium deficient animals, and from 13.3 +/- 4.3 to 32.9 +/- 0.6 in chronically water deprived animals, but showed little change in ACTH treated sheep, falling from 2.3 +/- 0.5 to 1.7 +/- 0.2 pmo1AI/ml plasma/h.

Prostaglandin synthesis inhibition with indomethacin in ACTH-induced hypertension.

The short- and long-term effects of indomethacin administration were examined in normotensive and ACTH-induced hypertensive conscious sheep. Indomethacin, 1 mg/kg/h for 60 min, caused a transient rise in mean arterial pressure (MAP) and calculated total peripheral resistance (CTPR) and a fall in cardiac output in normotensive sheep. In sheep with ACTH hypertension, these haemodynamic effects were prolonged. Indomethacin infusion at 3 mg/kg/day for 3 days had no observable haemodynamic or metabolic effects. Concomitant infusion of ACTH increased MAP and CTPR. These studies suggest prostaglandins play only a minor role in regulation of blood pressure in normal conscious sheep, but modulate the blood pressure rise in ACTH hypertension in sheep.

EFFECT OF ACTH ADMINISTRATION ON THE HAEMODYNAMIC RESPONSE TO ARGININE-VASOPRESSIN IN SHEEP

1. Blood pressure, heart rate and cardiac output were studied in intact conscious sheep during AVP infusion at 0.1, 0.25, 0.5 and 10 μg/min for 30 minutes to determine whether pressor responsiveness to AVP was altered in ACTH‐induced hypertension.

The Baroreceptor-Heart Rate Reflex in Acth Hypertension in Sheep

ACTH administration in sheep produces an adrenally dependent rise in blood pressure. Cardiac output and heart rate are usually increased. The precise mechanisms involved in the genesis of the hypertension are unclear. This study examines the sensitivity of the baroreflex heart rate response to phenylephrine hydrochloride and sodium nitroprusside before, during and after ACTH administration in sheep. During ACTH administration there was a sustained rise in blood pressure within 24 hours, whereas heart rate rose gradually. There was a sustained fall in baroreflex sensitivity to sodium nitroprusside within 24 hours, whereas baroreflex sensitivity to phenylephrine fell gradually over the first three days. The different time course of the change in sensitivity suggests that two different mechanisms are influenced by ACTH administration, for instance, changes in function in both cardiac vagal efferents and sympathetic pathways.

ACTH hypertension modifies the haemodynamic effects of prostacyclin infusions in sheep.

1. The haemodynamic effects of short‐term prostacyclin infusions (0.05‐0 50 /μg/kg per min) were investigated in conscious adult sheep.

Effects of converting enzyme inhibition with captopril on renal function in normal and ACTH treated sheep.

1. The effect on renal function in sheep of inhibiting converting enzyme with captopril was examined before and after 5 days ACTH administration.

Prostacyclin infusion does not prevent ACTH-induced hypertension in sheep

The present experiments examine the hemodynamic effects of an intravenous infusion of prostacyclin on the development of ACTH-induced hypertension in conscious sheep. Prostacyclin was infused at either 0.01 microgram/kg min-1 for 9 days or 0.25 microgram/kg min-1 for 4 days. At 0.01 microgram/kg min-1 prostacyclin had no effect on blood pressure in normotensive sheep or on the development of ACTH hypertension. Infusion at 0.25 microgram/kg min-1 increased heart rate, cardiac output and plasma renin concentration and decreased stroke volume and peripheral resistance in normotensive sheep. Despite these effects it did not prevent development of ACTH-induced hypertension. It is unlikely on the basis of these results that glucocorticoid-induced inhibition of vasodepressor prostacyclin and resulting increase in pressor responsiveness to circulating agonists is the primary cause of ACTH induced hypertension in sheep.

Haemodynamic and renin responses to prostacyclin infusion in Na depleted and Na restricted sheep

The haemodynamic and renin responses to prostacyclin (PGI2) infusion were examined in sheep during sodium depletion and dietary sodium restriction. The haemodynamic effects of PGI2 infusion in sodium depleted and sodium restricted sheep were similar to those obtained in the sodium replete animal. The renin proportionate response to PGI2 was not altered by sodium restriction but blunted by sodium depletion, compatible with the hypothesis that endogenous PGI2 is high in Na depletion.

A COMPARISON OF THE HAEMODYNAMIC EFFECTS OF DIETARY SODIUM RESTRICTION AND ACUTE SODIUM DEPLETION IN THE CONSCIOUS SHEEP

1. The use of a low Na, low K sorghum grain diet supplemented with intraruminal electrolyte infusions has enabled dietary manipulation of sodium status to be studied in the sheep.

EFFECTS OF β‐ADRENOCEPTOR BLOCKADE ON PROSTACYCLIN MEDIATED RENIN RELEASE IN SHEEP

1. The effect of prostacyclin (PGI2) infusion on plasma renin concentration (PRC) was examined before and after propranolol treatment in sheep.