SUMMARY1. The possible pressor effect of vasopressin immediately after acute haemorrhage has been studied using anaesthetized Brattleboro rats with diabetes insipidus and rats of the Long Evans parent strain.2. A blood loss of 0.5 % of the body weight caused a significant decrease in mean arterial blood pressure, measured 10 min later, in Brattleboro rats, whereas this degree of haemorrhage was non-hypotensive in the control Long Evans rats.Following subsequent blood losses (each of 0-5 % of the body weight), mean arterial blood pressure in Brattleboro rats was always significantly lower than in Long Evans rats.3. While no antidiuretic activity was at any time found in the plasma of Brattleboro rats, haemorrhages greater than 1 % of the body weight were associated with marked increases in plasma arginine vasopressin (AVP) of Long Evans rats. 4. When Brattleboro and Long Evans rats were subjected to a single haemorrhage of 2 % of the body weight, the immediate decrease in arterial blood pressure was similar in the two groups. However, 5 and 10 min after the haemorrhage the arterial blood pressure was significantly higher in the Long Evans rats. When vasopressin was infused into Brattleboro rats so that plasma levels of the hormone approached those found in Long Evans rats, the mean arterial blood pressure 0, 5 and 10 min after haemorrhage was similar to that in the Long Evans animals. 5. It is concluded that in the anaesthetized rat, vasopressin plays an important role in the regulation of arterial blood pressure during the period immediately following acute haemorrhage.

We re-examined, in the context of modern practice, plasma insulin and stress hormone concentrations in patients admitted to hospital with acute coronary syndromes. Venous blood sampling was carried out prior to anti-thrombotic therapy in 148 patients with myocardial infarction (MI); 76 patients with unstable angina (UA) pectoris were also studied, together with 27 patients with non-cardiac chest pain (NCP). There were significant progressive increases in the concentrations of catecholamines, cortisol, glucose and insulin from NCP to UA to MI patients. Hyperglycaemia (glucose >8 mmol/l) was present in over 50% of MI patients. The plasma cortisol and insulin levels were both significantly positively correlated with the glucose concentration on admission. Only the cortisol concentration was correlated with peak cardiac enzyme levels. The glucose and insulin concentrations on admission in 141 MI and UA patients were related to insulin resistance, as judged from subsequent insulin and glucose concentrations measured while fasting and during a glucose tolerance test. The product of admission insulinxglucose (divided by 25; the admission insulin-resistance index, or AIRI) was significantly correlated with indices of insulin resistance, and was significantly higher (approximately double) in the MI group (7. 81+/-0.76) and the UA group (6.88+/-1.19) than in the control NCP group (3.59+/-0.06; Kuskul-Wallis: P=0.0001), implying that the insulin levels in the first two groups were approximately twice as high as is appropriate for the glucose levels. The ethnic origin of 20% of the patients was the Indian subcontinent; admission insulin and glucose levels in this subgroup were higher than in the non-Asians across all the groups with chest pain. Cortisol was the only stress hormone that was raised in proportion to the size of the infarct, and is a likely partial cause of the elevation in blood glucose. The high insulin levels were related to the prevalence of insulin resistance, and this was particularly important in the Asian subgroup presenting with MI and UA. Thus it appears feasible to identify acute coronary syndrome patients who are insulin-resistant at a time (on admission) when alternative early therapeutic strategies can be instituted.

1. Renal function in anaesthetized Brattleboro rats with hereditary hypothalamic diabetes insipidus was studied with micropuncture techniques before, and 1-3 h after, a single injection of hydrochlorothiazide.2. In rats given hydrochlorothiazide and kept in sodium and water balance, total glomerular filtration rate and superficial nephron filtration rate were similar to values in control animals, whereas fractional fluid reabsorption in the proximal tubule (as evidenced by tubular fluid/plasma inulin concentration ratios) was slightly, but significantly, reduced. This suggests that hydrochlorothiazide may have a small direct inhibitory effect on proximal tubular reabsorption.3. When rats were given hydrochlorothiazide and the resultant extra urinary sodium losses were not replaced, there was a marked antidiuresis. In these animals total glomerular filtration rate was reduced by 23% and superficial nephron filtration rate by 27% when compared with values in control rats. Fractional proximal tubular fluid reabsorption increased significantly whereas absolute proximal fluid reabsorption was unaffected.4. It is concluded that the reduction in body sodium which follows acute hydrochlorothiazide administration over-rides any inhibitory effect of the drug on proximal tubular reabsorption, and leads instead to an increase in fractional fluid reabsorption at this site. This effect, combined with the fall in glomerular filtration rate, results in a greatly reduced delivery of fluid to the more distal nephron segments, and is probably largely responsible for the observed antidiuresis.

1. Brattleboro rats with hereditary diabetes insipidus were maintained in metabolism cages for 12-14 days. During the final 5-7 days hydrochlorothiazide was added to the food of half the animals, resulting in a sustained antidiuresis. At the end of this time all rats were anaesthetized and their renal function was investigated.2. Water, sodium and potassium excretion rates during anaesthesia were similar to their respective values during the final period in metabolism cages.3. Total glomerular filtration rate and superficial nephron filtration rate were similar in untreated and thiazide-treated animals. Fractional fluid reabsorption in proximal convoluted tubules, as measured by tubular fluidlplasma inulin concentration ratios in late surface convolutions, was moderately increased in the thiazide-treated rats, and was associated with a small reduction in the volume of fluid delivered to more distal nephron segments.4. The osmolality of renal papillary interstitial fluid from thiazide-treated rats was considerably greater than that from untreated animals. There was also a small increase in papillary fluid sodium concentration.5. It is concluded that the mechanism of the sustained antidiuresis during chronic hydrochlorothiazide administration in diabetes insipidus differs from that of the acute response.The changes in proximal tubular function during chronic thiazide treatment only partially account for the reduction in urine volume; it seems probable that the raised papillary osmolality, by enhancing water reabsorption at sites beyond the proximal tubule, makes a greater contribution to the antidiuresis.

SUMMARY1. The cardiovascular effects of an acute haemorrhage (2 % of the body weight)were studied over a 60 min period in three groups of rats: (a) Brattleboro rats with hereditary hypothalamic diabetes insipidus (b.d.i.) lacking circulating vasopressin, (b) control rats of the parent Long Evans (l.e.) strain, and (c) l.e. rats treated with an antagonist of the vascular action of vasopressin.2. Prior to the haemorrhage there were no significant differences between the three groups of rats with respect to mean arterial blood pressure, cardiac output, stroke volume or total peripheral resistance.3. Following the haemorrhage cardiac output and stroke volume were severely reduced in all three groups of rats. Total peripheral resistance was relatively unaffected in antagonist-treated l.e. rats and b.d.i. rats, but rose substantially in response to the loss of blood in the control l.e. group. Both total peripheral resistance and mean arterial blood pressure were markedly greater in the untreated l.e. control rats than in the other two groups of animals during the first 20 min after haemorrhage.4. The mean heart rate measured in Brattleboro rats was elevated compared with that of control l.e. rats throughout the experiment and, in addition, significantly greater than that of antagonist-treated l.e. rats during the first 40 min after the haemorrhage.5. Survival rate for the b.d.i. rats following the 2 % haemorrhage was lower than that for l.e. control rats and antagonist-treated l.e. rats.6. The results indicate that the recovery of the blood pressure following an acute arterial haemorrhage is significantly influenced by vasopressin, particularly during the first 20 min, and that the predominant effect of the hormone is to increase the total peripheral resistance. The higher mortality associated with volume depletion in the b.d.i. rats is unlikely to be directly related to the absence of the vascular action of vasopressin, since administration of the vasopressin antagonist to normal l.e. rats does not reduce their survival rate.