saralasin and Hemorrhage

Four groups of Sprague-Dawley rats were anaesthetized with isoflurane (ISO) (1.7% end-tidal concentration) in 40% oxygen, and mechanically ventilated. The animals were bled 15 mL kg-1 b.w. from the femoral vein over 10 min, followed by an observation period of 30 min. Ten minutes before haemorrhage each group of animals was pre-treated with intravenous injection/infusion of either: isotonic saline (Group B; CON; n=7), vasopressin V1-receptor antagonist [d(CH2)5Tyr(Me)AVP; 10 microg kg-1] (Group C; AVP-a; n=7), the non-selective angiotensin II receptor antagonist saralasin (10 microg kg-1 min-1) (Group D; SAR; n=7) or hexamethonium (10 mg kg-1) (Group E; HEX; n=7). A separate group of conscious animals were pre-treated with isotonic NaCl and subjected to the same haemorrhage protocol (Group A; AW; n=7). Mean arterial pressure (MAP), heart rate (HR) and blood gases were observed during the experiments. Only pre-treatment with SAR and HEX reduced MAP significantly. The pre-haemorrhage HR was only affected by HEX, which caused a reduction by 17%. The HR was significantly lower at the end of haemorrhage compared with pre-haemorrhage levels in all groups except that group treated with HEX. In that group the HR changed in the opposite direction. The ability to maintain MAP during haemorrhage, and the post-haemorrhage period, was significantly impaired in the groups treated with AVP-a, SAR or HEX compared with the group receiving NaCl. It is concluded that autonomic nervous activity is of major importance for the maintenance of MAP during isoflurane anaesthesia, whereas circulating angiotensin II and vasopressin levels contribute to a much smaller degree in this regard. General anaesthesia in combination with different degrees of neurohumoral blockade impairs the haemodynamic responses to blood loss, seen in conscious individuals. The impairment involves both the early and late phases during haemorrhage, as well as the post-bleeding recovery period. All three neurohumoral systems (autonomic nervous activity, angiotensin II and vasopressin) are of importance for regulating MAP during and after haemorrhage, although the autonomic nervous outflow appears to contribute to a larger extent.

Topics: Anesthesia; Anesthetics, Inhalation; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Blood Gas Analysis; Blood Pressure; Ganglionic Blockers; Heart Rate; Hemorrhage; Hexamethonium; Hydrogen-Ion Concentration; Isoflurane; Male; Neurotransmitter Agents; Rats; Rats, Sprague-Dawley; Saralasin

The role of brain angiotensin II (ANG II) in mediating cardiovascular, vasopressin, and renin responses to hemorrhage was assessed in conscious spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto (WKY) and Wistar rats. Intracerebroventricular administration of losartan (10 micrograms) and saralasin (1 microgram.microliter-1.min-1) produced a markedly greater fall in blood pressure and a reduced tachycardia during and after hemorrhage (15 ml/kg) compared with the artificial cerebrospinal fluid control in SHR and Wistar rats but not in WKY rats. Vasopressin release after hemorrhage was also impaired, but renin release was enhanced by intracerebroventricular ANG II antagonists in SHR and Wistar rats but not in WKY rats. Losartan and saralasin produced remarkably similar effects on the cardiovascular, vasopressin, and renin responses to hemorrhage. These data suggest that brain ANG II acting through AT1 receptors plays an important physiological role in mediating rapid cardiovascular regulation and vasopressin release in response to hemorrhage. The relative importance of brain angiotensin system may vary in different strains of rate.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Arginine Vasopressin; Biphenyl Compounds; Blood Pressure; Cerebral Ventricles; Heart Rate; Hemodynamics; Hemorrhage; Homeostasis; Imidazoles; Injections, Intraventricular; Losartan; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Wistar; Reference Values; Renin; Saralasin; Species Specificity; Tetrazoles; Time Factors

The present study examined the roles of the renin-angiotensin and autonomic nervous systems in cardiovascular homeostasis during slow progressive haemorrhage (20% of measured blood volume over 1h) in fetal (128-132 and 143-148 days gestation) and neonatal (5-9 and 12-20 days post-natal) sheep. Basal plasma renin activity (PRA) was not significantly different in the 4 sheep groups and increased to a similar degree (approximately 2 to 3-fold) during haemorrhage. Mean arterial pressure (MAP) exhibited modest falls in response to haemorrhage in all sheep groups and while heart rate (HR) was well maintained in the fetal groups there was a tendency to bradycardia in neonates. None of these responses was significantly different in age-matched fetal sheep subjected to bilateral vago-sympathectomy, cervical cord transection or bilateral nephrectomy, with the exception of PRA in the latter group which was close to zero throughout. Treatment with the angiotensin II (AII) antagonist, (Sar1-Ala8) AII (Saralasin), significantly increased basal PRA in both fetal and neonatal sheep (approximately 5 to 7-fold). The PRA response to haemorrhage was absent in neonatal sheep treated with Saralasin but significantly increased in fetal sheep. Saralasin significantly reduced resting MAP in both sheep groups and increased the hypotensive and bradycardic effects of haemorrhage in neonatal (approximately 3 to 5-fold) but not fetal sheep. It is concluded that in the perinatal period studied, fetal and neonatal sheep are equally well able to maintain cardiovascular homeostasis in response to moderate haemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analysis of Variance; Animals; Animals, Newborn; Autonomic Nervous System; Blood Pressure; Blood Volume; Cardiovascular Physiological Phenomena; Cardiovascular System; Fetal Diseases; Fetus; Heart Rate; Hematocrit; Hemorrhage; Homeostasis; Renin; Renin-Angiotensin System; Saralasin; Sheep; Sympathectomy

The contribution of the autonomic nervous system, angiotensin II (ANG II), and arginine vasopressin (AVP) to the control of blood pressure (BP) was examined in 12 chronically instrumented tethered monkeys. The vasopressin antagonist, [d(CH2)5AVP] (Manning Compound, MC), the ANG II antagonist, saralasin (SAR), and the ganglionic blocking drug, hexamethonium (Hx), were injected in a random sequence into the left atrium (LA) while BP and heart rate (HR) were monitored. When given as the first antagonist, MC caused a slight decrease in BP; SAR did not significantly decrease BP regardless of the sequence of administration, whereas Hx caused a consistent decrease in blood pressure of 35-50 mmHg. Seven (4 intact and 3 with renal denervation) additional animals were involved in hemorrhage experiments. Blood pressure was reduced to 50-60 mmHg by hemorrhage and then allowed to return spontaneously. Ten to 15 min after the end of the hemorrhage, MC was given. When blood pressure had stabilized, SAR was given. Blood pressure returned to 80-90 mmHg after the hemorrhage. MC did not affect the blood pressure recovery; however, saralasin reduced it to the post-hemorrhage levels. We would conclude that the sympathetic nervous system is the primary controlling mechanism for BP in the conscious primate, with AVP making a minor contribution. The release of renin would appear to be primarily under the control of the sympathetic nervous system.

Topics: Animals; Antihypertensive Agents; Arginine Vasopressin; Autonomic Nervous System; Blood Pressure; Denervation; Female; Hemorrhage; Hexamethonium; Hexamethonium Compounds; Kidney; Macaca mulatta; Male; Renin-Angiotensin System; Saralasin

Single injections of 4 ml/kg hypertonic NaCl (7.5%) resuscitate dogs from severe blood loss (40-45 ml/kg). Mechanisms involve osmolarity-dependent volume expansion, increased myocardial contractility, and vasodilation. The role of central angiotensinergic pathways in the hemorrhage-hypertonic resuscitation interaction was investigated through experiments performed on male pentobarbital sodium-anesthetized dogs bled to, and held at, 40 mmHg for 30 min. Dogs were treated with 4 ml/kg of 7.5% NaCl or 32 of 0.9% NaCl iv preceded by intracerebroventricular (ICV) injections of 150 micrograms saralasin, 20 micrograms arginine vasopressin inhibitor (AVPI), or 10 micrograms morphine. ICV saralasin and morphine inhibited the full recovery response to hypertonic NaCl, whereas AVPI had no such effect. Saralasin did not inhibit the recovery from hemorrhagic shock produced by large volume isotonic saline reexpansion. These data demonstrate an interaction between the central angiotensin system and small volume hypertonic resuscitation from severe hemorrhagic shock but not between this central system and large volume isotonic reexpansion of circulatory volume. In contrast, the central vasopressinergic system does not appear to be similarly involved.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Blood Volume; Brain; Dogs; Hemodynamics; Hemorrhage; Injections, Intraventricular; Male; Morphine; Osmolar Concentration; Resuscitation; Saline Solution, Hypertonic; Saralasin; Survival Analysis

The purpose of this study is to determine whether locally acting angiotensin II (ANG II) plays a direct role in the control of mesenteric blood flow after volume depletion in the anesthetized dog. Infusion of the ANG II receptor antagonist saralasin into the mesenteric artery at doses between 0.05 and 0.1 microgram.kg-1.min-1 attenuated the reduction in renal blood flow produced by intrarenal injection of ANG II. In contrast, infusion of saralasin at 0.01 microgram.kg-1.min-1 did not affect the change in renal blood flow produced by ANG II, indicating that at this dosage the antagonist did not leave the mesenteric circulation in pharmacologically significant quantities. ANG II produced a dose-dependent decrease in splanchnic blood flow when injected into the mesenteric artery. Simultaneous infusion of 0.01 microgram.kg-1.min-1 saralasin into the mesenteric artery blocked the action of up to 1 ng ANG II by 80%. Infusion of saralasin at 0.01 microgram.kg-1.min-1 into the mesenteric artery of hemorrhaged animals increased mesenteric blood flow without significantly affecting renal blood flow, blood pressure, or plasma renin activity. These data demonstrate that saralasin can be localized to the mesenteric circulation at a dose capable of inhibiting angiotensin action and that endogenous ANG II plays a direct, physiologically important local role in controlling splanchnic resistance after volume depletion.

Topics: Angiotensin II; Animals; Blood Pressure; Dogs; Dose-Response Relationship, Drug; Female; Hemorrhage; Male; Reference Values; Regional Blood Flow; Renal Circulation; Renin-Angiotensin System; Saralasin; Splanchnic Circulation

Naloxone reverses hemorrhagic hypotension in the conscious guinea-pig. Captopril and saralasin impede this naloxone effect, suggesting that angiotensin II is involved in naloxone action. This is compatible with previous work which has shown that B-endorphin inhibits the centrally mediated pressor action of angiotensin II, and that naloxone blocks this effect. Naloxone may be interacting with the postulated brain renin-angiotension II system or may be blocking the action of shock-induced circulating angiotensin II on a centrally located area such as the hypothalamus.

Topics: Animals; Blood Pressure; Captopril; Guinea Pigs; Hemorrhage; Hypotension; Hypothalamus; Naloxone; Neural Inhibition; Receptors, Opioid; Renin-Angiotensin System; Saralasin

This study was performed to assess the possible contribution of endogenous angiotensin II (AII) to the regulation of urinary kallikrein excretion. The AII antagonist saralasin or the saline vehicle was infused into the aorta above the renal arteries of pigs under halothane-O2/N2O anaesthesia. Systemic and renal functional parameters were followed for 140 min and during stimulation of the reninangiotensin system by haemorrhage. Urinary kallikrein excretion, determined as kininogenase activity, was increased immediately upon both initiation and termination of the 2 h saralasin infusion into pigs not subjected to haemorrhage. Renal cortical blood flow (RCBF) was maintained, in both saline and saralasin-treated animals at blood pressures as low as 70 mm Hg, while glomerular filtration rate was dissociated during saralasin infusion. As long as RCBF was maintained, urinary kallikrein excretion rate was elevated during the progressive hypotension in both saline and saralasin-treated animals. These findings confirm a close relationship between the maintenance of RCBF and increased activity of the kallikrein-kinin system whether or not AII is antagonized, and indicate that during haemorrhage the kallikrein-kinin system is stimulated by a mechanism not involving AII.

Topics: Angiotensin II; Animals; Glomerular Filtration Rate; Hemorrhage; Hypotension; Kallikreins; Renal Circulation; Saralasin; Swine; Time Factors

Angiotensin II (ANG II) is required for unimpaired adrenal reflex secretion of catecholamines after hemorrhage in the dog. To test if ANG II acts centrally, experiments were performed under general anesthesia on bilaterally or sham-nephrectomized dogs hemorrhaged at 25 ml/kg. Ventriculocisternal perfusion of ANG II or its antagonist saralasin was accomplished via needles inserted in the left lateral cerebral ventricle and cisterna magna. Mean arterial pressure and adrenal secretion of catecholamines were measured before and after hemorrhage. Nephrectomized dogs receiving only artificial cerebrospinal fluid (CSF) by ventriculocisternal perfusion had a very small adrenal response to hemorrhage compared with animals receiving ANG II intraventricularly (IVT) (at 10 and 100 pg . kg-1 . min-1). This effect of ANG II IVT also depended on the rate of IVT infusion. Peripheral infusion of ANG II (10 pg . kg-1 . min-1) had no effect on adrenal catecholamine secretion. Animals with intact kidneys given saralasin IVT (0.06 ng/min) responded similarly to nephrectomized dogs receiving only CSF IVT. Intravenous saralasin did not blunt the response to hemorrhage. Thus ANG II appears to support catecholamine secretion via a central mechanism. This mechanism is physiologically significant because either nephrectomy or functional elimination of ANG II by saralasin greatly attenuates the adrenal medullary response to hemorrhage in vivo.

Topics: Adrenal Glands; Angiotensin II; Animals; Brain; Dogs; Dopamine; Epinephrine; Hemorrhage; Kidney; Male; Nephrectomy; Norepinephrine; Renin-Angiotensin System; Saralasin; Time Factors

Patterns of vascular plasminogen activator activity (PAA) and of blood flow were compared in the renal cortex of pigs. The comparison was made in pigs with or without induction of hemorrhagic hypotension and continuous infusion of indomethacin (prostaglandin synthetase inhibitor) or saralasin (competitive inhibitor of angiotensin II). Blood flow was measured by radiolabelled microspheres. A significant decrease in the vascular PAA was observed only in saralasin treated animals (15% in not hemorrhaged pigs and 30% in the inner and 45% in the outer half of the renal cortex in hemorrhaged pigs). Changes in plasmin inhibitor activity in the renal cortex were not noted. No correlation could be seen between vascular PAA and changes in blood flow in the renal cortex or changes in the mean arterial blood pressure. The vascular fibrinolytic response to saralasin should be due to an effect of saralasin independent of the changes in blood flow induced by this agent.

Topics: Angiotensin II; Animals; Blood Pressure; Fibrinolysis; Hemorrhage; Indomethacin; Kidney Cortex; Plasminogen Activators; Prostaglandins; Saralasin; Swine

The participation of angiotensin II (ANG II) in the maintenance of arterial blood pressure during hypotensive hemorrhage was examined in unanesthetized, baroreceptor-denervated dogs. When mean aortic blood pressure was reduced to 69.0 +/- 2.2 mmHg, plasma renin activity increased from 0.6 +/- 0.3 ng ANG I X ml-1 X h-1 during the prehemorrhage control period to 4.5 +/- 1.6. Twenty minutes after the hemorrhage, mean aortic blood pressure rose to 78.9 +/- 3.1 mmHg. Subsequent infusion of the angiotensin II antagonist saralasin (5.2-14.0 micrograms X kg-1 X min-1) decreased mean aortic pressure to 59.6 +/- 3.3 mmHg. When 5% dextrose was infused in place of saralasin, mean aortic pressure was 79.3 +/- 4.3 mmHg. The lower aortic blood pressure caused by saralasin infusion was the result of a significant decrease in total peripheral resistance. Resistance was 10.3 +/- 3.2 mmHg X l-1 X min lower during saralasin infusion than during dextrose infusion. We conclude that baroreceptor reflexes are not essential for the elevation of plasma renin activity during hemorrhage. In baroreceptor-denervated dogs subjected to hypotensive hemorrhage, the increased formation of ANG II has a vasoconstrictor action that contributes to the maintenance of arterial blood pressure.

Topics: Angiotensin II; Animals; Aorta; Blood Pressure; Cardiac Output; Carotid Sinus; Denervation; Dogs; Heart Rate; Hemorrhage; Hypotension; Pressoreceptors; Renin-Angiotensin System; Saralasin; Vascular Resistance; Vasoconstriction

The effects of hemorrhagic hypotension on mean arterial pressure (MAP), cardiac output (CO), and its distribution were investigated in halothane-anesthetized rats using the radioactive microsphere technique. Hemorrhage (12 ml/kg) decreased MAP and CO, increased total peripheral resistance (TPR), and decreased blood flow (BF) to the heart, stomach, intestine, kidneys, skin, cecum, and colon. The effects of antagonists of vasopressin and the renin-angiotensin system on peripheral circulation following hypotensive hemorrhage were also examined using d(CH2)5Tyr(Me)AVP and saralasin, respectively. Injection of the vasopressin antagonist caused a reduction of MAP by reducing TPR and caused an increase of percent distribution of CO to the stomach, skin, cecum, and colon. Intravenous infusion of saralasin caused significant reductions of MAP by reducing TPR. Saralasin caused an increase of percent distribution of CO to the kidneys. The results show that both vasopressin and the renin-angiotensin systems participate in the control of MAP and peripheral vascular resistance following hypotensive hemorrhage in anesthetized rats.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Cardiac Output; Hemorrhage; Organ Specificity; Rats; Rats, Inbred Strains; Regional Blood Flow; Saralasin; Vascular Resistance

Alpha receptor and angiotensin II blockade were used to study renal cortical vasoconstrictor mechanisms during hemorrhage to 70 mmHg in chloralose-urethane anesthetized dogs. A freeze-dissection 133Xe disappearance technique was utilized to assess renal blood flow patterns. Hemorrhage alone caused a 30% decrease in total renal blood flow (TRBF) and a 50% decrease in outer cortical blood flow. Inner cortical flow decreased approximately 30%. Outer medullary blood flow decreased 25%. Renal arterial infusion of phentolamine beginning 20 min posthemorrhage produced no alteration in the expected posthemorrhage TRBF or its distribution. Plasma renin activity increased 6-7 fold in the hemorrhage group as well as in the hemorrhage with phentolamine group. Saralasin treatment beginning 20 min posthemorrhage produced a pattern in which neither TRBF nor cortical blood flow was significantly reduced by the hemorrhage. It therefore appears that angiotensin II is a renal cortical vasoconstrictor during hemorrhage. These data demonstrate that during the first 30 minutes of hemorrhage the renal cortical vasoconstriction is mediated by angiotensin II and appears to be independent of alpha-adrenergic mechanisms.

Topics: Angiotensin II; Animals; Dogs; Hemorrhage; Kidney Cortex; Phentolamine; Receptors, Adrenergic; Receptors, Adrenergic, alpha; Renal Circulation; Renin-Angiotensin System; Saralasin; Vasoconstriction

During fetal life, the autonomic nervous system is not fully mature, and it is likely that hormonal mechanisms play an important role in controlling cardiovascular function. In chronically instrumented fetal sheep, hemorrhage increased plasma renin activity and plasma angiotensin concentration significantly from 6.7 +/- 2.5 to 15.2 +/- 3.1 ng.ml-1.h-1 and from 74 +/- 19 to 182 +/- 43 pg/ml, respectively. Both mean arterial and venous blood pressures decreased initially from 45 to 35 Torr and from 3.5 to 2.5 Torr, respectively; then both returned to control values. Fetal heart rate decreased initially from 174 beats/min and then increased to 186 beats/min. To determine whether angiotensin had a role in mediating these responses to hemorrhage, we hemorrhaged a second group of fetuses before and during infusion of saralasin, a competitive antagonist of angiotensin. Hemorrhage during infusion of saralasin decreased heart rat from 170 to 145 beats/min and further decreased mean arterial pressure to 30 Torr. Cardiac output decreased from 436 +/- 25 to 368 +/- 30 ml.min-1.kg-1, and umbilical-placental blood flow decreased from 205 +/- 20 to 145 +/- 10 ml.min-1.kg-1. We conclude that the renin-angiotensin system plays a major role in the response to hemorrhage in fetal sheep.

Topics: Angiotensin II; Animals; Blood Pressure; Disease Models, Animal; Female; Fetal Blood; Fetal Diseases; Fetus; Heart Rate; Hematocrit; Hemorrhage; Pregnancy; Renin; Saralasin; Sheep

Topics: Angiotensin II; Animals; Dogs; Hemodynamics; Hemorrhage; Kidney; Pentobarbital; Prostaglandins; Regional Blood Flow; Saralasin; Sympathetic Nervous System; Synapses; Synaptic Transmission; Teprotide

Anesthetic agents have been shown to alter survival in animals subjected to hemorrhage. Since survival after hemorrhage is increased by inhibitors of the renin-angiotensin system, we asked whether anesthetic agents altered renin release during hemorrhage. We studied 33 rats which were subjected to one hour of hemorrhagic hypotension at a mean arterial pressure of 40 mm Hg. Animals were either awake or anesthetized with halothane or ketamine. Anesthesia alone did not alter plasma renin activity (PRA), whereas hemorrhage resulted in approximately a ten-fold increase in PRA in both awake and anesthetized animals. After the shed blood was returned to the animal, intravenous saralasin, an angiotensin II competitive inhibitor, produced a 21-24 mm Hg decrease in blood pressure in all animals, regardless of the severe hemorrhage is unaltered by halothane or ketamine anesthesia, that the renin-angiotensin system provides a similar amount of blood pressure support in both awake and anesthetized animals, and that the anesthetic influence on survival following severe hemorrhage does not result from anesthetic-induced alterations of the renin-angiotensin system.

Topics: Animals; Blood Pressure; Halothane; Hemorrhage; Ketamine; Male; Rats; Renin; Saralasin

Adrenal epinephrine (E) release after hemorrhage in anesthetized dogs is blunted by acute nephrectomy and restored by angiotensin II infusion. In the present study, we report the effect of converting enzyme inhibition by SQ 20881, a decapeptide, and of competition inhibition of angiotensin II by saralasin (1-Sar-8-Ala-Ang-II) on reflexly stimulated adrenal release of E and norepinephrine (NE) in three groups of acutely anephric dogs. Aortic catheters and adrenal vein to femoral vein Silastic shunts were placed in dogs anesthetized with pentobarbital and mechanically ventilated. Adrenal secretion rates were calculated from adrenal vein to aorta catecholamine concentration differences divided by measured adrenal venous flow. Catecholamine concentrations were determined with trihydroxyindole technique. Blood samples were obtained before and 15, 30, and 60 min after rapid hemorrhage to a stable mean arterial pressure of 50 mm Hg. Saralasin infusion (10 microgram/kg/min) supported adrenal E release in anephric hemorrhaged dogs toward secretion rates comparable to those seen in intact dogs. Anephric SQ 20881 (approximately 0.5 microgram/kg) recipients had delayed (60 min) augmented adrenal E and NE release after hemorrhage. In resting animals not reflexly stimulated by hypovolemia, neither drug provoked adrenal E or NE release. These results suggest an agonist effect of saralasin on reflex adrenal E release and increased responsiveness of the stimulated adrenal medulla under the influence of converting enzyme inhibition.

Topics: Adrenal Medulla; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Dogs; Epinephrine; Hemorrhage; Kidney; Nephrectomy; Reflex; Saralasin; Teprotide

This report describes the response of the renal circulation to prolonged hemorrhagic hypotension and reinfusion of blood, and to the effect of a variety of drugs (saralasin, indomethacin, and 6-hydroxydopamine, 6-OH-DA). Plastic microspheres were used to measure blood flow perfusing the entire kidney and also the outer cortex, inner cortex, and medulla of the kidney. Cardiac output was determined with a Doppler flow probe, and total and regional flows were calculated. Redistribution of blood flow from outer cortex to inner cortex and medulla occurred during hemorrhage and after administration of saralasin and 6-hydroxy-dopamine, while indomethacin did not alter intrarenal flow distribution. Total renal flow increased after reinfusion of blood and saralasin, but decreased after indomethacin. It did not change after 6-hydroxydopamine. The results demonstrate that changes in total and intrarenal flow occur independently and are probably due to different mechanisms.

Topics: Angiotensin II; Animals; Blood Pressure; Cardiac Output; Cats; Hemodynamics; Hemorrhage; Hydroxydopamines; Indomethacin; Kidney; Kidney Cortex; Kidney Medulla; Microspheres; Regional Blood Flow; Saralasin; Vascular Resistance

The role of the renin-angiotensin system in the maintenance of arterial pressure following hemorrhage was studied in conscious dogs. Hemorrhage (20 ml/kg body wt) decreased the mean arterial pressure, but compensatory mechanisms partially restored the arterial pressure toward normal. Plasma renin activity increased more than twofold following hemorrhage. To evaluate the role of endogenous angiotensin II in this compensatory response, a specific competitive antagonist of angiotensin II, 1-sarcosine-8-alanine-angiotensin II, was infused intravenously at 6.0 mug/kg min-1 for 30 min; the mean posthemorrhage arterial pressure decreased from 102 plus or minus 7 mmHg to 80 plus or minus 6 mmHg after 15 and 30 min of analog infusion (P less than 0.01 for both values). After a recovery period of 60 min, arterial pressure returned to pre-infusion levels. These results suggest that angiotensin II plays an important role in the short-term maintenance of arterial pressure following hemorrhage in the conscious animal.

Topics: Angiotensin II; Animals; Blood Pressure; Carotid Arteries; Dogs; Female; Hemorrhage; Homeostasis; Renin; Saralasin