Escape of Intestinal Resistance Vessels to Angiotensin II

1974 ◽  
Vol 52 (3) ◽  
pp. 458-464 ◽  
Author(s):  
J. Robert McNeill
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Intravenous Administration ◽  
Low Doses ◽  
Peak Response ◽  
Resistance Vessel ◽  
Resistance Vessels ◽  
Vessel Response ◽  
High Doses

The escape phase of the intestinal resistance vessel response to infusions of angiotensin II was studied in pentobarbital-anesthetized cats using a technique which did not involve cannulation of the arterial supply to the intestine. During intravenous infusions of angiotensin, the escape was 30% of the peak response. The escape was not related to the increase in arterial pressure. In low doses, the escape during intra-arterial infusions was similar to that observed during intravenous administration. Graded increases in the infusion dose of angiotensin produced increasing vasoconstriction except at high doses. The results indicate that escape of the intestinal resistance vessels to angiotensin is only partial and that a significant vasoconstriction is maintained. The results are consistent with the postulated role of endogenous angiotensin in the mechanism of the intestinal vasoconstriction following hemorrhage.

Response of rat jejunum to angiotensin II: role of norepinephrine and prostaglandins

1981 ◽  
Vol 240 (1) ◽  
pp. G17-G24 ◽  
Author(s):  
N. R. Levens ◽  
M. J. Peach ◽  
R. M. Carey ◽  
J. A. Poat ◽  
K. A. Munday
Keyword(s):  
Angiotensin Ii ◽  
Water Absorption ◽  
Rapid Onset ◽  
Inhibitory Response ◽  
High Dose ◽  
Low Doses ◽  
Slow Decay ◽  
High Doses ◽  
Stimulation Of

At low doses, angiotensin II (AII) stimulates jejunal sodium and water absorption in the pentobarbital sodium-anesthetized rat. This response to the hormone can be blocked by cycloheximide and has a rapid onset and decay, indicating that any protein involved must have a short half-life and/or fast turnover. At high doses, AII inhibits jejunal absorption by a process that does not involve protein synthesis and has a rapid onset but slow decay. The AII-induced inhibition of water absorption can be abolished, and a net stimulation ensues after pretreatment of the animals with meclofenamate or indomethacin, suggesting that at high doses AII stimulates intestinal prostaglandin biosynthesis. The AII analogue, [Sar1,Leu8]AII, significantly stimulated jejunal water absorption and was devoid of any inhibitory response at any dose administered. Simultaneous infusion of low doses of [Sar1,Leu8]AII and AII resulted in a stimulation of water transport, while simultaneous infusion of high dose [Sar1,Leu8]AII and AII also stimulated water absorption. It is suggested that the AII analogue is a full agonist with regard to stimulation of jejunal transfer but antagonizes the inhibitory response to high doses of AII. A model consistent with these data is discussed.

scholarly journals Decitabine: A Historical Review of the Development Process of an Epigenetic Drug

2020 ◽  
Vol 7 ◽  
Author(s):  
Cihan Zamur ◽  
Uğur Topal
Keyword(s):  
Development Process ◽  
Historical Review ◽  
Low Doses ◽  
Combination Therapies ◽  
Action Mechanism ◽  
Epigenetic Effect ◽  
Epigenetic Drug ◽  
Patient Responses ◽  
High Doses

Decitabine (5-aza-2p-deoxycytidine) is a hypomethylation agent with a double-action mechanism, these are the reactivation of silenced genes; exhibiting differentiation at low doses and showing cytotoxicity at high doses. Decitabine was used as a classic anticancer drug in the original studies in the 1980s, 1500 to 2500 mg/m2 per cycle was the maximum clinically tolerated dose. The dosage was reassessed after a better understanding of epigenetics in cancer and the role of decitabine in epigenetic (hypomethylation) therapy was obtained, in about 1/20th of the previous doses (i.e., 'optimal biological' doses modulating hypomethylation). It has been found that decitabine (100 to 150 mg / m2 per cycle) can be used in patients with myelodysplastic syndromes (MDS) and other myeloid tumors, with manageable side effects. Combination therapies which amplify the epigenetic effect of decitabine will most likely improve the patient responses and allow it to be used in the treatment of other malignancies.

Effect of baroreceptor denervation on stimulation of drinking by angiotensin II in conscious dogs

1991 ◽  
Vol 260 (3) ◽  
pp. E333-E337 ◽  
Author(s):  
C. K. Klingbeil ◽  
V. L. Brooks ◽  
E. W. Quillen ◽  
I. A. Reid
Keyword(s):  
Blood Pressure ◽  
Drinking Water ◽  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Carotid Sinus ◽  
Plasma Osmolality ◽  
Plasma Angiotensin ◽  
High Doses ◽  
Stimulation Of

Angiotensin II causes marked stimulation of drinking when it is injected centrally but is a relatively weak dipsogen when administered intravenously. However, it has been proposed that the dipsogenic action of systemically administered angiotensin II may be counteracted by the pressor action of the peptide. To test this hypothesis, the dipsogenic action of angiotensin II was investigated in dogs, in which low and high baroreceptor influences had been eliminated by denervation of the carotid sinus, aortic arch, and heart. In five sham-operated dogs, infusion of angiotensin II at 10 and 20 ng.kg-1.min-1 increased plasma angiotensin II concentration to 109.2 +/- 6.9 and 219.2 +/- 38.5 pg/ml and mean arterial pressure by 20 and 29 mmHg, respectively, but did not induce drinking. In four baroreceptor-denervated dogs, the angiotensin II infusions produced similar increases in plasma angiotensin II concentration and mean arterial pressure but, in contrast to the results in the sham-operated dogs, produced a dose-related stimulation of drinking. Water intake with the low and high doses of angiotensin II was 111 +/- 44 and 255 +/- 36 ml, respectively. The drinking responses to an increase in plasma osmolality produced by infusion of hypertonic sodium chloride were not different in the sham-operated and baroreceptor-denervated dogs. These results demonstrate that baroreceptor denervation increases the dipsogenic potency of intravenous angiotensin II and provides further support for the hypothesis that the dipsogenic action of intravenous angiotensin II is counteracted by the rise in blood pressure.

scholarly journals Acute sympathoexcitatory action of angiotensin II in conscious baroreceptor-denervated rats

2002 ◽  
Vol 283 (2) ◽  
pp. R451-R459 ◽  
Author(s):  
Ling Xu ◽  
Alan F. Sved
Keyword(s):  
Heart Rate ◽  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Sympathetic Nerve Activity ◽  
Baroreceptor Reflex ◽  
Ang Ii ◽  
Nerve Activity ◽  
Induced Hypotension ◽  
Baroreceptor Reflexes

Angiotensin II (ANG II) has complex actions on the cardiovascular system. ANG II may act to increase sympathetic vasomotor outflow, but acutely the sympathoexcitatory actions of exogenous ANG II may be opposed by ANG II-induced increases in arterial pressure (AP), evoking baroreceptor-mediated decreases in sympathetic nerve activity (SNA). To examine this hypothesis, the effect of ANG II infusion on lumbar SNA was measured in unanesthetized chronic sinoaortic-denervated rats. Chronic sinoaortic-denervated rats had no reflex heart rate (HR) responses to pharmacologically evoked increases or decreases in AP. Similarly, in these denervated rats, nitroprusside-induced hypotension had no effect on lumbar SNA; however, phenylephrine-induced increases in AP were still associated with transient decreases in SNA. In control rats, infusion of ANG II (100 ng · kg−1 · min−1 iv) increased AP and decreased HR and SNA. In contrast, ANG II infusion increased lumbar SNA and HR in sinoaortic-denervated rats. In rats that underwent sinoaortic denervation surgery but still had residual baroreceptor reflex-evoked changes in HR, the effect of ANG II on HR and SNA was variable and correlated to the extent of baroreceptor reflex impairment. The present data suggest that pressor concentrations of ANG II in rats act rapidly to increase lumbar SNA and HR, although baroreceptor reflexes normally mask these effects of ANG II. Furthermore, these studies highlight the importance of fully characterizing sinoaortic-denervated rats used in experiments examining the role of baroreceptor reflexes.

Oxidants and antioxidative defense

2002 ◽  
Vol 21 (2) ◽  
pp. 61-62 ◽  
Author(s):  
T Grune
Keyword(s):  
Free Radicals ◽  
Oxygen Free Radicals ◽  
Expression Patterns ◽  
Signal Transduction Pathways ◽  
Low Doses ◽  
The Past ◽  
Small Doses ◽  
Long Time ◽  
High Doses

The role of oxygen free radicals and other oxidants in several diseases has been well established over the past decade. Whereas it was long known that high doses of oxidants may damage or kill cells, the effect of low doses or long-time exposure to small flux rates of oxidants have been the focus of the free radical research until now. Here one has to take into account that most physiological and pathophysiological actions of oxidants and free radicals are based on the permanent action of small doses and flux rates. This includes effects of oxidants on signal transduction pathways and gene expression patterns. Therefore, only a few answers can be given today on the relevance of the effects of low doses of oxidants.

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

1976 ◽  
Vol 54 (3) ◽  
pp. 373-380 ◽  
Author(s):  
J. Robert McNeill ◽  
William C. Wilcox ◽  
Raoul Regnault
Keyword(s):  
Blood Pressure ◽  
Control System ◽  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Adrenal Glands ◽  
The Other ◽  
Volume Depletion ◽  
Competitive Antagonist ◽  
Vasoconstrictor Response ◽  
Resistance Vessels

Intravenous administration of furosemide (2 mg/kg) caused intestinal vasoconstriction in various groups of pentobarbital-anesthetized cats. [Sar1, Ala8]-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.

Role of angiotensin II in experimental renal hypertension in the rabbit

1975 ◽  
Vol 228 (1) ◽  
pp. 11-16 ◽  
Author(s):  
JA Johnson ◽  
JO Davis ◽  
B Braverman
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Renal Artery ◽  
Renal Hypertension ◽  
Plasma Renin ◽  
Control Group ◽  
Left Renal Artery ◽  
Chronic Hypertension ◽  
Group Of Seven

Hypertension was produced in rabbits by constricting the left renal artery; in nine rabbits the opposite kidney was removed and in eight rabbits the opposite kidney was left intact. To investigate the role of angiotensin II (A-II), 1-sarcosine-8-alanine angiotensin II, a competitive antagonist of A-II, was infused at 6 mug/min per kg body wt for 30 min. In a control group of seven unilaterally nephrectomized rabbits mean arterial pressure averaged 81 mmHg and infusion of the A-II antagonist did not alter the arterial pressure. In a group of Na-depleted rabbits, arterial pressure decreased from 81 to 63 mmHg (P less than 0.01) in response to the A-II analogue. Thirty days after renal artery constriction, seven of the nine one-kidney hypertensive rabbits had normal values for plasma renin activity (PRA) and during infusion of the A-II antagonist arterial pressure was unchanged. However, two rabbits had elevated PRA and the arterial pressure decreased during infusion of the angiotension analogue. In the two-kidney hypertensive rabbits, PRA was normal and arterial pressure was unchanged by infusion of the A-II antagonist. These studies provide evidence that hypertension developed with either a high or normal A-II plasma level in the one-kidney animals; the two-kidney rabbits developed chronic hypertension in which no role for A-II could be demonstrated.

Influence of Angiotensin II, Ouabain and Hydrostatic Pressure on Inulin and Electrolyte Concentration of Fluid Perfusing Pig Carotid Arteries in Vitro

1979 ◽  
Vol 56 (5) ◽  
pp. 445-453 ◽  
Author(s):  
J. K. Healy ◽  
A. J. Elliott ◽  
I. J. Oweczkin
Keyword(s):  
Angiotensin Ii ◽  
Hydrostatic Pressure ◽  
Arterial Pressure ◽  
Carotid Arteries ◽  
Sodium Concentration ◽  
High Dose ◽  
Electrolyte Homeostasis ◽  
Arterial Contraction ◽  
High Doses

1. Angiotensin II was infused into isolated, perfused pig carotid arteries. The perfusate leaving the arteries was sampled into an Auto-analyzer system which continuously monitored its composition. Arterial pressure was recorded. 2. Low, subpressor doses of angiotensin II raised the perfusate potassium concentration, whereas high doses, which produced contraction, lowered perfusate potassium and sodium concentrations. Inulin and chloride concentrations did not change. 3. The elevation of perfusate potassium with low angiotensin II dosage was appreciable compared with that caused by high doses of ouabain. 4. Neurotransmitter blockade did not alter the low- and high-dose angiotensin II effects. In other sequential dose studies, valine5-angiotensin II and isoleucine5-angiotensin II did not differ in their effects on perfusate composition or arterial contraction. 5. Mechanically increased hydrostatic pressure lowered perfusate sodium concentration, so that increased arterial pressure might have contributed to this aspect of high-dose angiotensin II effects. 6. These effects of angiotensin II might have physiological significance in relation to arterial smooth muscle and to electrolyte homeostasis.

Hypophysectomy and saralasin on mesenteric vasoconstrictor response to vasopressin

1979 ◽  
Vol 236 (2) ◽  
pp. H200-H205
Author(s):  
C. C. Pang ◽  
W. C. Wilcox ◽  
J. R. McNeill
Keyword(s):  
Angiotensin Ii ◽  
Plateau Phase ◽  
Dose Response Relationship ◽  
Competitive Antagonist ◽  
Stressed Animal ◽  
Vasoconstrictor Response ◽  
Resistance Vessels ◽  
Before And After ◽  
High Doses ◽  
Relationship Of

The dose-response relationship of the mesenteric resistance vessels to vasopressin was studied in anesthetized laparotomized cats before and after hypophysectomy and again during the plateau phase of the response to a prolonged infusion of [Sar1-Ala8] angiotensin II (saralasin), a competitive antagonist of angiotensin II. Hypophysectomy and saralasin each caused an increase in superior mesenteric arterial conductance. Before hypophysectomy infusion of 0.5 mU/(min.kg) of vasopressin caused mesenteric conductance to decrease from 0.168 to 0.156 ml/(min.kg.mmHg), a change of only 0.012 units. After hypophysectomy, the same dose reduced conductance from 0.227 to 0.179 mU/(min.kg.mmHg), a change of 0.048 units. During the plateau phase of the response to saralasin, 0.5 mU/(min.kg) of vasopressin reduced conductance from 0.281 to 0.201 ml/(min.kg.mmHg), a change of 0.079 units. Hypophysectomy and saralasin had little effect on the mesenteric vasoconstrictor response to high doses of vasopressin (2.0-10 mU/(min.kg). The ineffectiveness of low doses of vasopressin on the mesenteric resistance vessels of the intact anesthetized, surgically stressed animal may be due in part to the already constricted state of the bed caused by endogenous vasopressin and angiotensin and in part due to an opposing vasodilator influence, the reflex withdrawal of the vasoconstrictor effect of endogenous vasopressin.

Brain angiotensin II tonically modulates sympathetic baroreflex in rabbit ventrolateral medulla

1996 ◽  
Vol 271 (3) ◽  
pp. H1015-H1021 ◽  
Author(s):  
T. Saigusa ◽  
M. Iriki ◽  
J. Arita
Keyword(s):  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Inhibitory Effect ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Renal Sympathetic Nerve Activity ◽  
Baroreflex Function ◽  
Renal Sympathetic

The role of endogenous angiotensin II (ANG II) at the level of the rostral (RVLM) and caudal ventrolateral medulla (CVLM) in the control of sympathetic baroreflex function was investigated in urethan-anesthetized rabbits. The baroreflex relationship between mean arterial pressure and integrated renal sympathetic nerve activity (RSNA) was compared before and during microinfusion of saralasin, an ANG II receptor antagonist into RVLM or CVLM. The infusion of saralasin (20 pmol/min) into RVLM reduced the upper plateau, the range, and the range-dependent gain of the baroreflex, as well as the resting level of RSNA. The infusion of saralasin into CVLM augmented the upper plateau, the reflex range, and the range-dependent gain, whereas it did not alter the resting level of RSNA or mean arterial pressure. These results suggest that 1) the ANG II networks in RVLM are tonically active, influencing the resting level of the sympathetic outflow and facilitating the sympathetic baroreflex function, and 2) the ANG II networks in CVLM do not significantly influence the sympathetic activity in the resting state but exert an inhibitory effect on the baroreflex response when arterial pressure falls below the resting level.

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