saralasin and Shock

Topics: Animals; Captopril; Central Nervous System; Dogs; Fluid Therapy; Lung; Models, Biological; Resuscitation; Saline Solution, Hypertonic; Saralasin; Shock; Sodium Chloride

The interaction between hypoglycaemic stress and hypovolaemic stress in promoting adrenaline secretion from the adrenal medulla has been studied in anaesthetised and conscious rats. In anaesthetized rats, insulin (1 IU/kg, i.v.) markedly increased plasma adrenaline concentrations whereas blood sampling alone did not. The hypoglycaemic response to insulin was greatly reduced if donor blood was used instead of saline to replace the withdrawn blood. The hypoglycaemic response was abolished by captopril or saralasin. The results suggest that adrenaline secretion in response to hypoglycaemic stress in anaesthetized rats is potentiated by hypovolaemic activation of the renin-angiotensin system. In contrast, in fully conscious rats, the response to hypoglycaemia was not abolished by captopril, indicating that in the absence of barbiturate anaesthesia, the hypoglycaemic release of catecholamines is not potentiated by the renin-angiotensin system.

Topics: Adrenal Medulla; Animals; Epinephrine; Hypoglycemia; Male; Rats; Rats, Inbred BUF; Receptors, Angiotensin; Saralasin; Shock

Hypertonic saline resuscitation (HR, 7.5% NaCl, 4 ml/kg) effectively reverts severe hemorrhage, but a central neural component is probably involved in the survival response. This experiment examines the role of central angiotensinergic pathways in hemorrhage-hypertonic resuscitation interaction. Severely bled (43 +/- 2 ml/kg) pentobarbital-anesthetized dogs with chronically implanted cerebral ventricular cannulae were resuscitated with 4 ml/kg 7.5% NaCl, iv 10 min after intracerebroventricular injection of 0.5 ml normal saline (CT), 150 micrograms saralasin (in 0.5 ml saline, SR), or 10 mg captopril (in 0.5 ml saline, CP). All 10 SR-treated dogs died 2-6 h after HR. Their arterial pressure and cardiac index initially recovered to near pre-hemorrhage levels, but gradually decreased thereafter, base excess remaining at severe metabolic acidosis levels throughout. All CT- and 8/10 CP-treated dogs survived indefinitely, with near normal arterial pressure, cardiac index and base excess levels. It is therefore concluded that the inhibition of central angiotensinergic sites with the competitive antagonist saralasin effectively prevents survival after HR, whereas inhibition of angiotensin converting enzyme by captopril in cerebrospinal fluid is virtually ineffective.

Topics: Animals; Captopril; Cardiac Output; Dogs; Injections, Intraventricular; Male; Renin-Angiotensin System; Resuscitation; Saline Solution, Hypertonic; Saralasin; Shock

Both angiotensin and alpha-adrenergic blocking agents reduce arterial blood pressure in hypovolemic states. We have compared the effects of an angiotensin antagonist (saralasin) and an alpha-adrenergic blocking agent (phenoxybenzamine) in supramaximal dosage on cardiac output, total peripheral resistance, and venous tone in rabbits rendered hypovolemic by restriction of sodium intake, supplemented by a furosemide-induced diuresis 48 h prior to study. Saralasin (10 microgram/kg per min) reduced arterial blood pressure significantly (-15 +/- 1.2 mmHg) despite an unchanged cardiac output (P less than 0.025) due to a fall in total peripheral resistance. Phenoxybenzamine (5 mg/kg) induced a much larger fall in arterial blood pressure (-28 +/- 3.6 mmHg), despite an identical reduction in total peripheral resistance, because cardiac output also fell (+/- 9 ml/kg per min). The reduction in cardiac output was associated with a significant increase in hindlimb venous distensibility (P less than 0.001) after alpha-adrenergic blockade. Saralasin, conversely, had no influence on venous tone. Adrenergic mechanisms contribute to cardiovascular homeostasis through an influence on both arteriolar and venous tone, whereas the effect of angiotensin is directed entirely to the arteriolar side of the circulation.

Topics: Animals; Blood Pressure; Cardiac Output; Female; Phenoxybenzamine; Rabbits; Receptors, Adrenergic; Receptors, Adrenergic, alpha; Receptors, Angiotensin; Receptors, Cell Surface; Saralasin; Shock; Vascular Resistance