angiotensin-i and Hemorrhage

Angiotensin II, the biologically active component of the renin-angiotensin system, acts throughout the body to produce an impressive number of cardiovascular, endocrine, metabolic, and behavioral effects. Major actions include elevation of arterial pressure, stimulation of aldosterone secretion, and a variety of effects on the kidneys, brain, and pituitary. Investigation of the role of the renin-angiotensin system in physiological regulation has been greatly facilitated by the availability of specific inhibitors of the formation or actions of angiotensin II, most notably converting-enzyme inhibitors and angiotensin receptor antagonists. Studies with these agents have clearly shown that the renin-angiotensin system plays an important role in the defense of body balance and blood pressure in hypovolemic state, including sodium deficiency and hemorrhage. The inhibitors also lower blood pressure in some forms of hypertension, and converting-enzyme inhibitors are proving to be effective antihypertensive agents.

Topics: Aldosterone; Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Animals; Blood Pressure; Brain; Hemorrhage; Humans; Hypertension; Kidney; Peptidyl-Dipeptidase A; Pituitary Gland; Renin; Renin-Angiotensin System; Water-Electrolyte Balance

Angiotensin II (AngII) immunoreactive cells, fibers and receptors, were found in the parvocelluar region of paraventricular nucleus (PVNp) and AngII receptors are present on vasopressinergic neurons. However, the mechanism by which vasopressin (AVP) and AngII may interact to regulate arterial pressure is not known. Thus, we tested the cardiovascular effects of blockade of the AngII receptors on AVP neurons and blockade of vasopressin V1a receptors on AngII neurons. We also explored whether the PVNp vasopressin plays a regulatory role during hypotension in anesthetized rat or not. Hypovolemic-hypotension was induced by gradual bleeding from femoral venous catheter. Either AngII or AVP injected into the PVNp produced pressor and tachycardia responses. The responses to AngII were blocked by V1a receptor antagonist. The responses to AVP were partially attenuated by AT1 antagonist and greatly attenuated by AT2 antagonist. Hemorrhage augmented the pressor response to AVP, indicating that during hemorrhage, sensitivity of PVNp to vasopressin was increased. By hemorrhagic-hypotension and bilateral blockade of V1a receptors of the PVNp, we found that vasopressinergic neurons of the PVNp regulate arterial pressure towards normal during hypotension. Taken together these findings and our previous findings about angII (Khanmoradi and Nasimi, 2017a) for the first time, we found that a mutual cooperative system of angiotensinergic and vasopressinergic neurons in the PVNp is a major regulatory controller of the cardiovascular system during hypotension.

Topics: Angiotensin I; Angiotensin II; Angiotensin II Type 2 Receptor Blockers; Animals; Arterial Pressure; Hemorrhage; Hypotension; Hypovolemia; Male; Nerve Net; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Vasopressins

Angiotensin-(1-7) (Ang-[1-7]) is present in the brain of normotensive Sprague Dawley (SD) rats, and its hypothalamic content is elevated in TGRmRen2(27) rats (TGR) with renin dependent transgenic hypertension. The purpose of the present study was to determine the role of intrabrain Ang-(1-7) in the regulation of cardiovascular functions in SD and TGR rats under resting conditions and during haemodynamic challenge produced by rapid bleeding. Two groups of experiments were performed on conscious SD and TGR rats that were chronically instrumented with a lateral cerebral ventricle (LCV) cannula and an intraarterial catheter. Blood pressure (MAP) and heart rate period (Hp=distance between two systolic peaks) were continuously monitored: 1) under resting conditions during an LCV infusion of either artificial cerebrospinal fluid (aCSF, 5 microl/hr) or Ang-(1-7) in aCSF (100 pmol/5 microl/hr), and 2) before and after haemorrhage performed during LCV infusion of either aCSF or Ang-(1-7) antagonist (A-779, 4 nmol/5 microl/hr). Cerebroventricular infusion of Ang-(1-7) did not affect baseline MAP in the SD rats but it caused a significant decrease in blood pressure in the TGR rats. In the control experiments, haemorrhage significantly reduced MAP in the SD and TGR rats and heart rate in the TGR rats. Cerebroventricular infusion of Ang-(1-7) antagonist eliminated posthaemorrhagic hypotension in both strains and bradycardia in the TGR rats. The results indicate that intrabrain Ang-(1-7) may contribute to posthaemorrhagic hypotension and bradycardia. Moreover, the manner in which it centrally regulates the cardiovascular functions in the SD and TGR rats may be considerably different.

Topics: Adaptation, Physiological; Angiotensin I; Angiotensin II; Animals; Animals, Genetically Modified; Blood Pressure; Cerebral Ventricles; Cerebrospinal Fluid; Heart Rate; Hemorrhage; Hypertension; Hypotension; Hypothalamus; Injections, Intraventricular; Peptide Fragments; Rats; Rats, Sprague-Dawley; Renin; Shock, Hemorrhagic; Species Specificity

To evaluate the effects of angiotensins acting at the rostral ventrolateral medulla (RVLM) on the cardiovascular adjustments following haemorrhage.. Changes in mean arterial pressure (MAP) and heart rate (HR) produced by micro-injections of angiotensin II (Ang II) and angiotensin (Ang)-(1-7) and different angiotensin antagonists into the RVLM of anaesthetized rats submitted to haemorrhage, were determined.. Experiments were performed in 79 urethane-anaesthetized male Wistar rats. Ang-(1-7) (2.5 and 25 pmol), Ang II (25 pmol), [Sar1,Thr8]-Ang II (non-selective angiotensin antagonist, 0.2 nmol), A-779 (Ang-(1-7) antagonist, 0.1 nmol), losartan (AT1 Ang II receptor antagonist, 0.2 nmol) or vehicle (200 nl) were bilaterally micro-injected into the RVLM under basal conditions or 30 min after blood withdrawal (0.6 ml/100 g bodyweight). In additional groups, [Sar1,Thr8]-Ang II, A-779, losartan or vehicle were micro-injected into the RVLM 10 min before bleeding to uncover a possible role of endogenous peptides during haemorrhage.. The pressor effect produced by Ang II micro-injection was not altered by haemorrhage. Conversely, haemorrhage significantly increased the magnitude and duration of the pressor effect of Ang-(1-7) at the RVLM. The fall in MAP induced by haemorrhage was similar after micro-injection of vehicle or A-779. However, micro-injection of [Sar1,Thr8]-Ang II significantly reduced the fall in MAP after haemorrhage. A similar finding was obtained with micro-injection of losartan. In addition, while RVLM micro-injection of [Sar1,Thr8]-Ang II or losartan 30 min after blood withdrawn produced MAP changes that were similar to that observed in control animals, micro-injection of A-779 did not significantly alter baseline MAP.. These results suggest that changes in the RVLM reactivity to Ang-(1-7) but not Ang II may contribute to the haemodynamic adjustments triggered by acute reductions in blood volume. The data obtained with [Sar1,Thr8]-Ang II and losartan suggest a primary inhibitory role for endogenous Ang II at the RVLM during haemorrhage.

Topics: Angiotensin I; Angiotensin II; Animals; Blood Pressure; Heart Rate; Hemorrhage; Male; Peptide Fragments; Pressoreceptors; Rats; Rats, Wistar; Sympathetic Nervous System

To investigate the role of renal sympathetic nerves in modulating cardiovascular and endocrine responses to hemorrhage early in life, we carried out three experiments in conscious, chronically instrumented lambs with intact renal nerves (intact; n = 8) and with bilateral renal denervation (denervated; n = 5). Measurements were made 1 h before and 1 h after 0, 10, and 20% hemorrhage. Blood pressure decreased transiently after 20% hemorrhage in intact lambs and returned to control levels. In denervated lambs, however, blood pressure remained decreased after 60 min. After 20% hemorrhage, heart rate increased from 170 +/- 16 to 207 +/- 18 beats/min in intact lambs but not in denervated lambs, in which basal heart rates were already elevated to 202 +/- 21 beats/min. Despite an elevated plasma renin activity (PRA) measured in denervated (12.0 +/- 6.4 ng ANG I . ml-1 . h-1) compared with intact lambs (4.0 +/- 1.1 ng ANG I . ml-1 . h-1), the increase in PRA in response to 20% hemorrhage was similar in both groups. Plasma levels of arginine vasopressin increased from 11 +/- 8 to 197 +/- 246 pg/ml after 20% hemorrhage in intact lambs but remained unaltered in denervated lambs from baseline levels of 15 +/- 10 pg/ml. These observations provide evidence that in the newborn, renal sympathetic nerves modulate cardiovascular and endocrine responses to hemorrhage.

Topics: Angiotensin I; Animals; Animals, Newborn; Arginine Vasopressin; Blood Pressure; Denervation; Heart Rate; Hemodynamics; Hemorrhage; Kidney; Renal Circulation; Renin; Renin-Angiotensin System; Sheep; Time Factors; Vascular Resistance

In this study we investigated the effects of dehydration and hemorrhage on circulating levels of the heptapeptide, angiotensin(1-7). In water-deprived rats, a twofold increase in plasma angiotensin(1-7) was associated with similar increases in plasma renin activity, and angiotensin I and angiotensin II levels. In salt-loaded rats, plasma angiotensin(1-7) levels increased fourfold; however, other components of the renin-angiotensin system were suppressed or unchanged. In salt-loaded rats, increases in plasma angiotensin II levels in response to hemorrhage in normal rats were severely blunted, whereas angiotensin(1-7) plasma levels increased proportionately to the loss of blood volume. These results suggest that angiotensin(1-7) plasma concentration can be selectively regulated during dehydration and hemorrhage.

Topics: Angiotensin I; Angiotensin II; Animals; Hemorrhage; Male; Peptide Fragments; Radioimmunoassay; Rats; Rats, Wistar; Sodium Chloride; Water Deprivation; Water-Electrolyte Imbalance

Ac3-Proteinase from the venom of Agkistrodon acutus was isolated in a homogeneous form by a previously published method. Ac3-Proteinase possessed lethal, hemorrhagic, caseinolytic, azocaseinolytic, dimethylcaseinolytic and hide powder azure hydrolytic activities. These activities were inhibited when Ac3-Proteinase was incubated with the metal chelators ethylenediaminetetraacetic acid (EDTA), ethyleneglycol-bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA), tetraethylenepentamine (TEP), 1,10-phenanthroline, phosphoramidon or beta-mercaptoethanol. The toxin also hydrolyzed the oxidized A and B chains of both insulin and fibrinogen. The cleavage sites in the oxidized B chain of insulin were identified as His(10)-Leu(11), Ala(14)-Leu(15), Tyr(16)-Leu(17) and Phe(24)-Phe(25). The A alpha chain of fibrinogen was digested first followed by hydrolysis of the B beta chain. Toxicological and biochemical properties of Ac3-Proteinase were investigated further and are reported in this paper.

Topics: Angiotensin I; Animals; Caseins; Creatine Kinase; Crotalid Venoms; Endopeptidases; Hemorrhage; Mice; Necrosis; Peptides; Substrate Specificity; Thrombin

Topics: Angiotensin I; Angiotensin II; Animals; Brain; Female; Goats; Hemorrhage; Rana temporaria; Reflex; Renin-Angiotensin System; Thirst; Vasopressins; Water; Water-Electrolyte Balance

The effects of angiotensin converting enzyme inhibitor (CEI) upon blood pressure and plasma aldosterone (PA) were studied in rabbits with a simultaneous infusion of angiotensin I (ANG I) or with hemorrhagic hypotension. Pretreatment with CEI (SQ 20881), 1.0 mg/Kg, inhibited the effects of infused ANG I, 30 ng/Kg/min, upon PA and blood pressure at 30 min of the infusion, but the inhibition on PA was not significant at 60 min of the infusion. The same dose of CEI was ineffective in blocking the effect of 100 ng/Kg/min of ANG I on PA and blood pressure even at 30 min of the infusion. In rabbits with hemorrhagic hypotension, injection of CEI resulted in the decrement in blood pressure, whereas no decrement in blood pressure was observed in normal control rabbits. This study suggests that CEI exerts it's effect in part by inhibiting conversion of ANG I to angiotensin II (ANG II), but this can't exclude other mechanisms.

Topics: Aldosterone; Angiotensin I; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animals; Blood Pressure; Bradykinin; Female; Hemorrhage; Hypotension; Oligopeptides; Rabbits; Teprotide

1. Renin activity in rabbit plasma increases after acidification (pH 3.3), probably due to activation of an inactive form of renin. 2. Both active and inactive renin in plasma increase after haemorrhage. This stimulus does not change the relative proportions of the two forms. 3. After ligation of the renal blood vessels neither form of renin increases in response to haemorrhage. 4. One day after bilateral nephrectomy no inactive renin could be demonstrated in plasma. 5. In the rabbit, therefore, the kidney is a major source of the inactive renin in plasma.

Topics: Angiotensin I; Animals; Female; Hemorrhage; Kidney; Male; Rabbits; Renin