Release of beta-lipotropin- and beta-endorphin-like material induced by angiotensin in the conscious rat.
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1 The influence of the renin-angiotensin system on plasma beta-endorphin-like immunoreactivity (beta-EI) was investigated in the conscious rat by use of a radioimmunoassay for beta-endorphin without prior extraction.2 Intravenous infusion of angiotensin I, II or (des-1-Asp)angiotensin II (angiotensin III) caused a dose-dependent increase in plasma beta-EI, angiotensin III infusion being less effective than angiotensin I or II. The plasma adrenocorticotrophin (ACTH) levels too were elevated by angiotensin II. The receptor antagonist, saralasin, prevented the angiotensin II-induced beta-EI release as did dexamethasone pretreatment.3 Both the release of beta-EI and the pressor response to angiotensin I were abolished by the converting enzyme inhibitor, captopril (SQ 14225). In contrast, captopril did not affect the action of angiotensin II.4 In view of the appreciable cross-reactivity of beta-lipotropin (beta-LPH) in our assay, plasma beta-EI was analysed by Sephadex G-50 chromatography. In plasma extracts of angiotensin II-infused rats, immunoreactivity corresponding to human beta-endorphin comprised about 49% of the total immunoreactivity, whereas 51% co-migrated with human beta-LPH.5 The increase in plasma levels of beta-EI elicited by angiotensin II was diminished by about 35% in rats with a hereditary absolute lack of vasopressin (Brattleboro rats), when compared to normal rats.6 These results suggest that the renin-angiotensin system can stimulate the secretion of beta-LPH and beta-endorphin with ACTH from rat anterior pituitary. One link in mediating the response appears to be vasopressin. The physiological function remains to be defined. (+info)
The half-lives of angiotensin II, angiotensin II-amide, angiotensin III, Sar1-Ala8-angiotensin II and renin in the circulatory system of the rat.
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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. (+info)
Inhibition of the vagal component of the baroreceptor-cardioinhibitory reflex by angiotensin III in dogs and sheep.
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Angiotensin II inhibits baroreceptor-evoked activity in cardiac vagal motoneurones. Because angiotensin III [( des-1-Asp ]angiotensin II) is a less potent pressor agent than angiotensin II, and has been reported not to share some of the actions of angiotensin II within the central nervous system, its influence on central vagal pathways was examined here. In unanaesthetized sheep equipressor doses of angiotensins II and III similarly inhibited the baroreceptor-cardioinhibitory reflex, a reflex which is almost wholly dependent on cardiac vagal activity. In anaesthetized dogs, equipressor doses of angiotensin II and III were equally effective in inhibiting the cardiac vagal activity usually evoked by rises in arterial pressure. This was established by direct recordings of activity in single cardiac vagal efferent nerve fibres. Direct recordings from single baroreceptor nerves in anaesthetized dogs showed that the angiotensins do not depress the receptor responses to elevations in blood pressure. It is concluded that equipressor doses of angiotensin III and angiotensin II inhibit central vagal pathways to the same extent. (+info)
Angiotensin I, II, and III in sheep. A model of angiotensin production and metabolism.
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The arterial and central venous concentrations of angiotensin I (AI), Val5-angiotensin II ([Val5]AII), and Val5-angiotensin III ([Val5]AIII(2-8)) were quantitatively determined in conscious sheep before and after sodium depletion. All three angiotensins were elevated in blood with progressive sodium loss. During sodium deficiency the arteriovenous concentration ratios (A:V) of AI, [Val5]AII, and [Val5]AIII(2-8) were found to be 0.48 +/- 0.03 (n = 9), 1.30 +/- 0.05 (n = 16), and 1.52 +/- 0.05 (n = 11) respectively. Intravenous infusion of [Val5]AII or [Val5]AIII(2-8) significantly elevated the A:V of respective angiotensins, being 2.09 +/- 0.28 (n = 5) for [Val5]AII and 2.2 +/- 0.37 (n = 6) for [Val5]AIII(2-8). The blood clearance rates of exogenous [Val5]AII and [Val5]AIII(2-8) in sodium-depleted sheep were calculated to be 135 +/- 15 liter/hr (n = 10) and 140 +/- 13 liter/hr (n = 10) respectively. Based on these experimental data, a steady-state model of angiotensin metabolism was constructed. If it is assumed that endogenous arterial blood [Val5]AII and [Val5]AIII(2-8) cleared metabolically at a similar rate as exogenous arterial blood angiotensins, it can be calculated that at steady-state 55% of the arterial [Val5]AII concentration was derived from the peripheral vascular bed. For [Val5]AIII(2-8), 63% of the arterial concentration was derived from the pulmonary circulation. The concentration of [Val5]AIII(2-8) in arterial blood was 42% of [Val5]AII. (+info)
Angiotensin inhibits action of vagus nerve at the heart.
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The effects of angiotensin II and angiotensin III (Des-Asp angiotensin II) on cardiac vagal nerve endings were studied in intact dogs and in isolated guinea-pig atria. Decreases in heart rate evoked by electrical stimulation of the peripheral end of the cut vagus were attenuated in the presence of angiotensin II and angiotensin III. (+info)
Effects of diltiazem hydrochloride on pressor and steroidogenic actions of angiotensins and norepinephrine in man.
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The effect of diltiazem hydrochloride (DTZ), a calcium-antagonist, on pressor and steroidogenic action of angiotensin II (AII), angiotensin III (AIII) and norepinephrine (NE) was studied in 5 normal men. AII, AIII and NE were infused intravenously for 50 min from 0900 hr at a rate of 20 ng/kg/min, 100 ng/kg/min and 200 ng/kg/min, respectively. DTZ was infused intravenously alone or in combination with each of these pressor substances at a rate of 1 mg/min from 0910 hr to 0930 hr. DTZ alone did not cause significant changes in blood pressure (BP) and plasma aldosterone concentration (P1 Aldo). On the other hand, DTZ combined with AII, AIII or NE significantly inhibited the rise in BP induced by these pressor substances. DTZ also inhibited the NE-induced increase in P1 Aldo, whereas it did dot alter AII-, or AIII-induced increase in P1 Aldo. These results indicate that in normal men pressor actions of AII, AIII and NE are calcium-dependent and calcium ions are also involved in NE-induced increase in P1 Aldo. (+info)
Contractile responses of isolated dog mesenteric arteries to angiotensin I, II and III.
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The addition of angiotensin (Ang-) I, II and III caused a dose-dependent contraction of helically cut strips of dog mesenteric arteries. Tachyphylaxis developed following repeated additions of angiotensins. Average median effective concentrations of Ang-I, II and III were 3.7, 0.8 and 2.5 X 10(-8) M, respectively. Contractile responses to the angiotensins were attenuated to a similar extent by Ang-II antagonists, Sar1 Ileu8 Ang-II and Sar1 Ala8 Ang-II, but were unaffected by phentolamine, methysergide and diphenhydramine. The response to Ang-I was significantly reduced by treatment with bradykinin-potentiator B, while the response to Ang-II was not influenced. It may be concluded that Ang-I, II and III produce contractions possibly by activation of same Ang-II receptors and that contractions induced by Ang-I are associated, to some extent, with a conversion to Ang-II in the arterial wall. (+info)
Increased sodium appetite in the rat induced by intracranial administration of components of the renin-angiotensin system.
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1. Intracranial injections of components of the renin-angiotensin system in rats in normal water and Na balance caused an immediate thirst followed by a progressive increase in Na appetite during a test session which lasted 18 h. The effect on water and Na intake was dose-dependent. 2. Long-term (7 day) infusions of angiotensin II into the third cerebral ventricle at rates of 1 or 10 pmol h-1 produced large and sustained increases in intake of water and 2 . 7% NaCl. Intakes sometimes exceeded 100 ml 2 . 7% NaCl per day but quickly fell to normal when the infusion was stopped. 3. Intracranial injection or infusion of carbachol caused a transient increase in water intake but had no effect on the intake of NaCl. 4. The Na appetite induced by intracranial injection of angiotensin was specific for Na since rats offered a choice of water and equimolar concentrations of NaCl and KCl took only water and NaCl. This resembles the pattern seen in Na-depleted rats. 5. Increased Na appetite was not secondary to increased water intake since it occurred when only 2 . 7% NaCl was available to drink. 6. Increased Na appetite was not secondary to natriuresis since, first, the angiotensin-stimulated rats went into positive Na balance, secondly, intracranial renin did not cause increased Na excretion in Na-loaded rats and thirdly, anureic rats showed a significant Na appetite in response to renin. 7. These results suggest that angiotensin in the brain may play a role in the development of Na appetite. (+info)