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At least 19 recordsLinked to original sources
PubMed1979

Brain angiotensin II binding and central [Sar1,Ala8]angiotensin responses in normal rats and the New Zealand strain of genetically hypertensive rats.

1. Specific angiotensin II (ANGII) receptor binding was measured in regions of the brains of the New Zealand gentically hypertensive and normal rats. 2. ANGII receptor binding was consistently lower in the septum, midbrain, thalamus and posterior medulla of the genetically hypertensive rats than in normal rats. 3. Blood pressure responses to intraventricular injections of ANGII and an ANGII antagonist [Sar1,Ala8]angiotensin were studied in conscious and pentobarbitone-anaesthetized genetically hypertensive and normal rats. In conscious rats no significant difference between the two strains of rat was detected. 4. In pentobarbitone-anaesthetized rats intraventricular injection of 40 microgram of [Sar1,Ala8]angiotensin had a hypotensive effect which was three times greater in the genetically hypertensive rats than that observed in normal rats. The latency of this hypotensive effect was longer than the latency of the hypertensive effect of ANGII. 5. The drinking responses to intraventricular injections of ANGII were similar in genetically hypertensive and normal rats. 6. The physiological role of the ANGII system is discussed and it is concluded that an abnormality of this system in the brain may well be responsible for the hypertension found in the genetically hypertensive rat.

Angiotensin II↗
PubMed1976

Effect of an angiotensin antagonist, Sar1-Ala8-angiotensin II on physiological thirst.

Initially it was shown that infusion of Sar1-Ala8-angiotensin II (P113) into the third ventricle (50-100 mug/ml at 1.1 ml/hr) effectively abolished the large water intake induced 1-2 min after beginning an intracarotid infusion of angiotensin II at 800 ng/min which causes an unphysiologically high concentration of angiotensin II in cerebral arterial blood. Infusion of P113 (50-100 mug/ml at 1.1 ml/hr) into the third brain ventricle for 20 min prior to and during presentation of water to sheep after 48 hr water deprivation did not reduce water intake. Water intake associated with rapid food intake or carotid artery infusion of hypertonic NaC1 was similarly unaffected by intraventricular administration of P113. While high concentrations of angiotensin II are dipsogenic in sheep, these results cast doubt on a contributory role for angiotensin II in thirst caused by water depletion or rapid food intake in the sheep.

Angiotensin II↗
PubMed1977

The course of arterial pressure and the effect of Sar1-Thr8-angiotensin II in a new model of two-kidney hypertension in conscious dogs.

1. We describe a new method of producing two-kidney hypertension in dogs by a two-step procedure with complete occlusion of a renal artery 2 weeks after it was partially constricted. 2. Control mean arterial pressure (96 +/- 3 mmHg) of nine conscious, trained dogs rose to 107 +/- 3 mmHg 2 weeks after partial constriction of a renal artery, and it stabilized at a sustained hypertensive plateau (124 +/- 7 mmHg) 3 weeks after complete occlusion. 3. Intravenous infusion of an angiotensin II antagonist (Sar1-Thr8-angiotensin II) caused arterial pressure to fall during the acute but not the chronic phase of renal hypertension. In this latter phase plasma renin activity had returned to control values. 4. We conclude that the renin-angiotensin system appears not to be directly involved in the chronic phase of two-kidney hypertension in the dog.

Angiotensin II↗
PubMed1977

Plasma catecholamines and the pressor response to Sar1-Ala8-angiotensin II in man.

1. The initial blood pressure response to saralasin (Sar1-Ala8-angiotensin II) infusion was examined in 15 normal subjects, eight patients with untreated essential hypertension and 65 patients established on chronic haemogialysis (including six anephric patients), and related to measurements of plasma renin activity (PRA), angiotensin II, plasma catecholamines (noradrenaline and adrenaline), blood volume and extracellular fluid volume ([35S]sulphate space or exchangeable sodium). 2. A transient rise in arterial pressure, maximum after 5-6 min, occurred in all normal subjects, patient with essential hypertension and anephric patients, and in 41 of the 59 dialysis patients with kidneys. 3. In the normal subjects, saralasin infusion resulted in a significant rise in plasma noradrenaline (mean increase 360%, P less than 0-02) without change in plasma adrenaline concentration. The change in noradrenaline was significantly related to the change in mean blood pressure (P less than 0-05) and was similar to the response to 5 min of a 40 degree head-up tilt. 4. An increase in plasma noradrenaline also occurred in dialysis patients (P less than 0-005) but the change in mean blood pressure with saralasin in this group was inversely related to PRA (P less than 0-001) and angiotensin II (P less than 0-001), directly related to blood volume (P less than 0-001), but unrelated to the change in plasma noradrenaline. 5. The pressor response to saralasin may be mediated not only by angiotensin-like action on vascular receptors but also by an action on the central or peripheral autonomic nervous system.

Adolescent↗
PubMed1978

Effect of administration of Sar1-Ala8-angiotensin II during the development and maintenance of renal hypertension in the rat.

1. Sar1-Ala8-Angiotensin II (an angiotensin antagonist) was infused in rats during the development and maintenance of renal hypertension produced by aortic ligation between renal arteries. 2. In the early phase (5 and 12 days after ligation), infusion of the antagonist markedly decreased blood pressure although it did not reach normal pressures. Later (day 40) only a modest decrease in blood pressure was noted. 3. Removal of the small left kidney always decreased the blood pressure to normal pressures. 4. It is concluded that the renin-angiotensin system is the major pressor component in the initiation of this hypertension. Later, other factors of renal origin assume a pressor function.

Angiotensin II↗
PubMed1979

The influence of sar1 ala8 angiotensin II (saralasin) on plasma aldosterone in hypertensive patients.

The effect of a 4-hour infusion of the angiotensin II analogue sar1 ala8 angiotensin II (saralasin) on plasma aldosterone concentration (PAC) was assessed in relation to plasma renin activity (PRA) in 12 patients, both on normal sodium intake and after marked sodium depletion. On normal sodium intake the response of PAC to saralasin was variable; following sodium depletion saralasin induced a marked decrease in PAC in 11 of 12 patients. The extent of the change in PAC induced by saralasin correlated closely with log PRA. The data indicate that saralasin is also a competitive antagonist of the effect of the endogenous renin-angiotensin system (RAS) on the adrenal cortex, with agonistic activity appearing at low levels of PRA. The effect of sodium depletion on AC appears to be mediated to a major degree by the RAS.

Adrenal Cortex↗
PubMed1976

Agonist and antagonist effects of Sar1-ala8--angiotensin II in salt-loaded and salt-depleted normal man.

1 Three normal subjects were infused with Sar1-ala8-angiotensin II (Saralasin, P113) whilst on a high sodium (200 mEq + normal diet) and a low sodium (10 mEq diet) intake. 2 On the high sodium intake when angiotensin II and plasma renin activity (PRA) were suppressed, P113 infusion (5-10 mug kg-1 min-1) caused a slight rise in BP and a marked drop in urine flow and sodium excretion, with a fall in glomerular filtration rate, and effective renal plasma flow. 3 On the low sodium intake, when angiotensin II and PRA were increased, P113 infusion (5-10 mugkg-1 min-1) caused no change in blood pressure, urine flow or sodium excretion. However, when P113 was infused at an incremental rate starting at 0.25 mug kg-1 min-1 there was a fall in standing BP, which was maximal at an infusion rate of 1 mug kg-1 min-1, and this fall in standing BP was largely abolished as the rate of infusion was increased to 10 mug kg-1 min -1. 4 These results show firstly that angiotension II is involved in maintaning standing blood pressure during dietary sodium depletion in normal man and secondly that P113 does have agonist as well as antagonist activity in normal man, the effect depending on the level of angiotension II and sodium intake. When looking for angiotensin II mediated hypertension it may ne important to use an incremental rate of infusion of P113 as the agonist activity of larger doses may mask its hypotensive action.

Angiotensin II↗
PubMed1978

The half-lives of angiotensin II, angiotensin II-amide, angiotensin III, Sar1-Ala8-angiotensin II and renin in the circulatory system of the rat.

1. Methods are described for estimating the half-life of angiotensin analogues and renin in the rat, from the time course of the blood pressure changes they evoke. 2. The following half-life values were measured: angiotensin II, 16 +/- 1 sec; angiotensin III, 14 +/- 1 sec; angiotensin II-amide, 15 +/- 1 sec; Sar1-Ala8-angiotensin II, 6.4 +/- 0.6 min; renin, 3.0 +/- 0.4 min. The distribution volume of angiotensin was found to be 18 ml./kg body wt. 3. It is inferred that the Asp1 residue does not reduce the rate of angiotensin II catabolism, but that substitution of this residue by sarcosine may inhibit catabolism while substitution by asparagine has no effect. 4. Five experimental criteria were identified which indicate that these methods give reliable estimates of the half-life. It is suggested that these results are more accurate than most previous half-life estimates. 5 When tachyphylaxis to angiotensin II-amide occurs, the pressor activity of the plasma is not reduced.

Angiotensin Amide↗
PubMed1976

Effect of (Sar1, Ala8)-angiotensin II and hypophysectomy on the intestinal resistance vessels and blood pressure following furosemide-induced volume depletion.

Intravenous administration of furosemide (2 mg/kg) caused intestinal vasoconstriction in various groups of pentobarbital-anesthetized cats. (Sar1, Ala 8)-angiotensin II, a specific competitive antagonist of angiotensin II, was infused 60 min after administration of furosemide, a time when the intestinal vasoconstrictor response to the diuretic was maximal or near maximal. In hypophysectomized animals, infusion of the antagonist abolished the intestinal vasoconstriction and caused a significant fall in arterial pressure even when the intestinal nerves and adrenal glands remained intact. In contrast, the antagonist had little effect when the pituitary gland remained intact. The results suggest that endogenous angiotensin and vasopressin are overlapping mechanisms which constrict the intestinal resistance vessels and support arterial pressure following furosemide-induced volume depletion. In the absence of one control system, the other compensates to maintain the responses.

Adrenal Glands↗
PubMed1978

Hypotensive effect of [Sar1,Thr8]angiotensin II in spontaneously hypertensive sodium-depleted rats.

Under inactin anesthesia, intravenous infusion of [Sar1,Thr8]angiotensin II produced a hypotensive effect in young spontaneously hypertensive rats (SHR) treated with furosemide and in mature SH rats fed a low-sodium diet. The angiotensin antagonist also lowered blood pressure of young and mature SH rats receiving a normal diet. Deoxycorticosterone acetate (DOCA) plus saline reversed the hypotensive effect of [Saru,Thr8]angiotensin II in young SH rats, but did not do so in mature SH rats. Plasma renin activity (PRA) was not significantly changed by anesthesia. Furosemide or the low-sodium diet significantly increased PRA in young and mature SH rats. In contrast, DOCA plus saline significantly reduced PRA in both young and mature SH rats. However, there was no correlation between PRA and the action of the angiotensin II antagonist. These data suggest that the renin-angiotensin system is involved in genetic hypertension.

Aging↗
PubMed1979

Effect of angiotensin II receptor blockade by [Sar1-Ala8]angiotensin II in hemorrhagic shock.

An angiotensin II receptor antagonist, [Sar1-Ala8]angiotensin II (saralasin), was infused at 60 (microgram/kg)/h into cats to examine its effect in hemorrhagic shock. Aprotinin (1,000 (KIU/kg)/h) was also administered to cats to determine how kinin inhibition effects angiotensin receptor blockade in shock. Saralasin was infused into shocked and sham-shocked cats. Aprotinin was administered to additional cats receiving either saralasin or its vehicle. Hemorrhaged cats treated with saralasin revealed a postoligemic preservation of mean arterial bloood pressure and superior mesenteric artery blood flow (SMAF). Final pressures were 48 +/- 12 mmHg and 81 +/- 9 mmHg with vehicle and saralasin treatment, respectively, and final SMAF were 2.5 +/- 0.5 (ml/kg)/min in cats receiving vehicle and 5.5 +/- 0.6 (ml/kg)/min in those receiving saralasin. Total plasma proteolysis was diminished by both saralasin and aprotinin, exhibiting elevations of free amino-nitrogen groups of 2.5-fold and 2-fold over initial as compared to a 3.5-fold elevation in vehicle-treated shocked cats. Myocardial depressant factor (MDF) activities were also suppressed by saralasin compared to shocked cats receiving vehicle (24 +/- 4 units vs. 59 +/- 3 units). These results indicate that blockade of angiotensin II actions in hemorrhagic shock is beneficial.

Amino Acids↗
PubMed1977

[Hemodynamic effects of sar1-ala8-angiotensin in patients with renovascular hypertension (author's transl)].

In 7 hypertensive patients with renal artery stenosis and in 1 patient with hypertension and unilateral pyelonephritic nephrophthisi the influence of the angiotensin II antagonist, saralasin on systemic hemodynamics was studied. In the patients with normal renin infusion of saralasin produced an increase in total peripheral resistance, in patients with elevated renin a decrease in peripheral resistance was observed. In 3 patients who had extremely high renin levels while under sodium saralasin produced a dangerous drop in blood pressure concomitant with a marked decrease in cardiac output and in central venous pressure, heart rate remained unchanged or increased just slightly. The findings suggest that in patients with high plasma renin peripheral resistance, venous tone, venous retrun, and cardiac output are to a large extent controlled by circulating angiotensin II.

Adult↗
PubMed1978

Effect of the specific angiotensin antagonist (Sar1) (Ala8) angiotensin II on blood pressure and the renin-angiotensin system in the conscious pregnant ewe and fetus.

A direct relationship was found between maternal diastolic blood pressure and simultaneously measured angiotensin II (All) levels (P less than 0.001) in chronically cannulated pregnant ewes. The infusion of Saralasin to the ewe resulted in a dose-dependent fall in blood pressure (P less than 0.005), the magnitude of which was proportional to the initial All levels (P less than 0.025). Plasma renin and All levels rose significantly during the infusion. No consistent fetal effects were seen. The infusion of normal saline had no effect on blood pressure or hormone levels. Thus it seems likely that the renin-angiotensin system is involved with the maintenance of normal blood pressure in the pregnant sheep. Fetal blood pressure either fell significantly or was unchanged following direct infusion of Saralasin. This may be related to development of the beta-adrenergic nervous system. The renin-angiotensin system may be more important in cardiovascular homeostasis in the immature than in the adult animal.

Aldosterone↗
PubMed1979

Absence of adrenergic mediation of agonist response to [Sar1,Ala8]angiotensin II in conscious normotensive and hypertensive dogs.

1. In the conscious normotensive and two-kidney Goldblatt hypertensive dog a transient agonist response to the intravenous infusion of saralasin (1 microgram min-1 kg-1)was manifested by a small increase in blood pressure (6-12) mmHg) and 28-30% increase in renal vascular resistance. 2. These increases in blood pressure and renal vascular resistance were unaffected by administration of either phentolamine or guanethidine. 3. The agonist response in the conscious dog is most likely accounted for by a direct action of saralasin on vascular angiotensin receptors.

Adrenergic alpha-Agonists↗
PubMed1979

Effect of Sar1-ala8-angiotensin II on blood pressure and renin in Bartter's syndrome, before and after treatment with prostaglandin synthetase inhibitors.

Three patients suffering from Bartter's syndrome were studied before and after 5 days of treatment with the prostaglandin synthetase inhibitors, aspirin and indomethacin. Saralasin was given by intravenous infusion in increasing doses from 0.6 to 42 micrograms/min.kg/BW. During saralasin infusion a blood pressure reduction was observed in all patients. Aspirin treatment did not affect this response and nor did it affect other manifestations of the syndrome. Indomethacin treatment changed the blood pressure response to saralasin in such a way that the blood pressure was increased in one patient and was unchanged in the other. Indomethacin also tended to normalize other features of Bartter's syndrome, such as the hyperreninaemia and angiotensin unresponsiveness, but did not affect the hypokalaemia. The saralsin effect on blood pressure is thus evidently inversely related to the prevailing activity of the renin-angiotensin system in this condition also, and the patients obviously depended on the renin-angiotensin system to maintain their blood pressure. Our findings, together with data in the literature, indicate that angiotensin unresponsiveness of the vascular bed is not a primary feature in Bartter's syndrome. Chloride loss is currently thought to be the basic abnormality and this may link the Bartter's syndrome with other diseased states characterized by chloride loss, such as the syndrome of habitual vomiting and chronic treatment with loop diuretics.

Adolescent↗