Angiotensin II In Rats Research Articles

Micro-lightguide spectrophotometry assessment of hepatic and intestinal microcirculation in endotoxemic rats during intravenous treatment with angiotensin II

IntroductionDuring septic shock, impairment of microcirculation leads to enhanced permeability of intestinal mucosa triggered by generalized vasodilation and capillary leak. Intravenous angiotensin II (AT-II) has been approved for the treatment of septic shock; however, no in-vivo data exist on the influence of AT-II on hepatic and intestinal microcirculation. Material and methodsSixty male Lewis rats were randomly assigned to six study groups (each n = 10): sham, lipopolysaccharide-induced septic shock, therapy with low- or high-dose AT-II (50 or 100 ng/kg/min, respectively), and septic shock treated with low- or high-dose AT-II. After median laparotomy, hepatic and intestinal microcirculation measures derived from micro-lightguide spectrophotometry were assessed for 3 h and included oxygen saturation (SO2), relative blood flow (relBF) and relative hemoglobin level (relHb). Hemodynamic measurements were performed using a left ventricular conductance catheter, and blood samples were taken hourly to analyze blood gasses and systemic cytokines. ResultsAT-II increased mean arterial pressure in a dose-dependent manner in both septic and non-septic animals (p < 0.001). Lower hepatic and intestinal SO2 (both p < 0.001) were measured in animals without endotoxemia who received high-dose AT-II treatment, however, significantly impaired cardiac output was also reported in this group (p < 0.001). In endotoxemic rats, hepatic relBF and relHb were comparable among the treatment groups; however, hepatic SO2 was reduced during low- and high-dose AT-II treatment (p < 0.001). In contrast, intestinal SO2 remained unchanged despite treatment with AT-II. Intestinal relBF (p = 0.028) and interleukin (IL)-10 plasma levels (p < 0.001) were significantly elevated during treatment with high-dose AT-II compared with low-dose AT-II. ConclusionsA dose-dependent decrease of hepatic and intestinal microcirculation during therapy with AT-II in non-septic rats was observed, which might have been influenced by a corresponding reduction in cardiac output due to elevated afterload. While hepatic microcirculation was reduced during endotoxemia, no evidence for a reduction in intestinal microcirculation facilitated by AT-II was found. In contrast, both intestinal relBF and anti-inflammatory IL-10 levels were increased during high-dose AT-II treatment.

Neurons of the median preoptic nucleus contribute to chronic angiotensin II-salt induced hypertension in the rat.

Experiments were designed to test the hypothesis that median preoptic (MnPO) neurons are necessary for the full hypertensive response to chronic angiotensin II (AngII) in rats consuming a high salt diet. The MnPO is implicated in many of the physiologic actions of AngII, primarily acting as a downstream nucleus to AngII binding at circumventricular organs such as the organum vasculosum of the lamina terminalis (OVLT). We have previously shown a prominent effect of lesion of the OVLT on the chronic hypertensive effects of AngII in rats consuming high salt. Additionally, we have shown that lesion of the MnPO attenuated the hypertensive response to chronic intravenous infusion of AngII in rats. However, whether MnPO neurons or fibers of passage contribute to this response is not clear. Male Sprague Dawley rats were randomly assigned to either sham (SHAM; n=8) or ibotenic acid lesion of the MnPO (MnPOx; n=6). In the MnPOx group, 200 nl of ibotenic acid in phosphate buffer saline (5 μg/μl) was injected into each of 3 predetermined coordinates targeted at the entire MnPO. After a week of recovery, rats were instrumented with radiotelemetric pressure transducers, provided 2.0% NaCl diet and distilled water ad libitum and given another week to recover. After 3 days of baseline measurements, osmotic minipumps were implanted subcutaneously in all rats for administration of AngII at a rate of 150 ng/kg/min. Blood pressure measurements were made for 14 days after minipump implantation. By day 7 of AngII treatment, blood pressure responses appeared to plateau in both groups while the hypertensive response was markedly attenuated in MnPOx rats (MnPOx, 122 ± 6 mmHg; SHAM, 143 ± 8 mmHg). These results support the hypothesis that neurons of the MnPO are involved in the central pathway mediating the chronic hypertensive effects of AngII in rats consuming a high salt diet.

Angiotensin type 1 receptor blockage reduces l-dopa-induced dyskinesia in the 6-OHDA model of Parkinson's disease. Involvement of vascular endothelial growth factor and interleukin-1β

Non-neuronal factors such as angiogenesis and neuroinflammation may play a role in l-dopa induced dyskinesias (LID). Vascular endothelial growth factor (VEGF) and proinflammatory cytokines such as interleukin-1β (IL-1β) have been found to be involved in LID. The renin–angiotensin system (RAS) is involved in the inflammatory response and VEGF synthesis via type 1 (AT1) receptors. However, it is not known whether the RAS plays a role in LID and whether AT1 antagonists could constitute a useful therapy against LID. In this study, we investigated whether manipulation of brain RAS is effective in preventing LID. Blocking AT1 receptors with candesartan significantly reduces LID in the 6-OHDA rat model. Chronic dopaminergic denervation induces an increase in striatal levels of VEGF and IL-1β. Dyskinetic animals showed significantly higher levels of VEGF and IL-1β in the lateral striatum and the substantia nigra, as revealed by western blot and real time-PCR analyses. Interestingly, animals treated with both candesartan and l-dopa displayed significantly lower levels of VEGF, IL-1β and dyskinesia than those treated with l-dopa alone. The stimulatory effect of angiotensin II (AII) on VEGF expression was confirmed by the addition of AII to primary mesencephalic cultures and intraventricular administration of AII in rats. The results of the present study reveal for the first time that blockage of AT-1 receptors reduces LID. A candesartan-induced decrease in VEGF and IL-1β may be responsible for the beneficial effects, suggesting the brain RAS as a new target for LID treatment in PD patients.

The neurogenic phase of angiotensin II-salt hypertension is prevented by chronic intracerebroventricular administration of benzamil.

Hypertension induced by chronic administration of angiotensin II (AngII) is exacerbated by high‐salt intake. Previous studies have demonstrated that this salt‐sensitive component is due to increased activity of the sympathetic nervous system, suggesting an interaction of plasma AngII with sodium‐sensitive regions of the brain. This study tested the hypothesis that the salt‐sensitive component of AngII‐induced hypertension would be prevented by intracerebroventricular (ICV) administration of the sodium channel/transporter blocker benzamil. Male Sprague Dawley rats were instrumented to measure mean arterial pressure (MAP) by radio telemetry and for ICV administration of benzamil or vehicle and placed in metabolic cages for measurement of sodium and water intake and excretion. In rats consuming a high‐salt diet (2.0% NaCl) and treated with ICV vehicle, administration of AngII (150 ng/kg/min, sc) for 13 days increased MAP by ~30 mmHg. ICV administration of benzamil (16 nmol/day) had no effect during the first 5 days of AngII, but returned MAP to control levels by Day 13. There were minimal or no differences between ICV vehicle or benzamil groups in regards to sodium and water balance. A lower dose of ICV benzamil administered ICV at 8 nmol/day had no effect on the MAP response to AngII in rats on a high‐salt diet. Finally, in contrast to rats on a high‐salt diet, AngII had negligible effects on MAP in rats consuming a low‐salt diet (0.1% NaCl) and there were no differences in any variable between ICV benzamil (16 nmol/day) and ICV vehicle‐treated groups. We conclude that the salt‐sensitive component of AngII‐induced hypertension is dependent on benzamil blockable sodium channels or transporters in the brain.

OVLT lesion decreases basal arterial pressure and the chronic hypertensive response to AngII in rats on a high-salt diet.

We have reported that lesion of the organum vasculosum of the lamina terminalis (OVLT) has no effect on basal levels of mean arterial pressure (MAP) but abolishes the hypertensive effects of angiotensin II (AngII) in rats consuming a normal-salt diet. These results suggest that the OVLT does not contribute to regulation of MAP under conditions of normal salt intake, but it is an important brain site for the hypertensive actions of AngII. The OVLT has been proposed as a major sodium sensor in the brain and the hypertensive effects of AngII are exacerbated by high-salt intake. Therefore, the objective of this study was to investigate the role of the OVLT during AngII-induced hypertension in rats fed a high-salt diet. Male Sprague-Dawley rats underwent sham (Sham; n = 9) or OVLT lesion (OVLTx; n = 8) surgery and were placed on a high-salt (2% NaCl) diet. MAP was measured by radio telemetry during three control days, 10 days of AngII infusion (10 ng/kg/min, i.v.), and a 3-day recovery period. MAP was significantly lower in OVLTx (97 ± 2 mmHg) compared to Sham (106 ± 1 mmHg) rats during the control period (P < 0.05). Moreover, the chronic pressor response to AngII was markedly attenuated in OVLTx rats. MAP increased 58 ± 3 mmHg in Sham rats by Day 10 of AngII compared to a 40 ± 7 mmHg increase in OVLTx rats (P < 0.05). We conclude that (1) the OVLT regulates the basal levels of MAP in rats consuming a high-salt and (2) the OVLT is an important brain site of action for the pathogenesis of AngII-salt hypertension in the rat. Supported by HL076312.

Long-lasting inhibition of angiotensin response in rats by depot administration of octanoyl-[Leu8]-angiotensin II.

Depot administration of a lipophilic angiotensin II (AII) antagonist was tested for obtaining prolonged inhibition of the pressor response to AII in rats. Intramuscular injections of 1.5 or 5.0 mg of octanoyl-[Leu8]AII (oct-LAII), in oil solution produced the same degree of AII inhibition either 6 h or 24 h after the injection. The inhibition was comparable to that expected from the continuous intravenous infusion of oct-LAII at the rate of 1.2 microgram kg-1 min-1. The prolonged effect of intramuscular injections of oct-LAII in oil solution may be useful for chronic studies of physiopathological states involving the renin-angiotensin-aldosterone system.

Mesenteric vascular resistance responses to chronic angiotensin II (AngII) are dependent on dietary salt intake

We previously reported that total peripheral resistance is increased by AngII in rats consuming a high salt diet, and that this response is attenuated by denervation of the mesenteric vascular bed. Based on these observations, we hypothesize that mesenteric vascular resistance (MVR) is increased in AngII rats consuming a high salt diet. In this study, rats on either a high (2%) or low (0.1%) NaCl diet were chronically instrumented for continuous measurement of MAP and superior mesenteric artery blood flow (MBF). AngII was infused (150 ng/kg/min, sc) for 14 days preceded by 4 days of control. MVR was calculated as MAP/MBF. 0.1% NaCl rats showed minimal responses to AngII. MAP during the control period, and Days 1 and 14 of AngII were 100±2, 103±4 and 104±4 mm Hg respectively. In contrast, in 2% NaCl rats, MAP was 111±3 during control and 126±5 and 140±10, on Days 1 and 14 of AngII. MBF was fairly constant within the two groups. In 0.1% NaCl rats MBF was 12.5±0.9, 12±1, 12.5±0.4 mL/min during control and Days 1 and 14 of AngII. In 2% NaCl rats, MBF averaged 10±1, 8±1, 10±2 mL/min over the same time period. MVR remained stable in 0.1%NaCl rats during control and Days 1 and 14 of AngII (8.0±0.7, 8.6±0.9, 8.3 ±0.6 a.u. respectively). In contrast, MVR increased from a control level of 11±1, to 16±3 on Day 1, and 14±4 a.u. on Day 14 of AngII. We conclude that AngII increases MVR in rats consuming a high salt diet but not those on a low salt diet. HL064178.

Renal angiotensin II concentration and interstitial infiltration of immune cells are correlated with blood pressure levels in salt-sensitive hypertension

Renal immune cell infiltration and cells expressing angiotensin II (AII) in tubulointerstitial areas of the kidney are features of experimental models of salt-sensitive hypertension (SSHTN). A high-salt intake tends to suppress circulating AII levels, but intrarenal concentrations of AII have not been investigated in SSHTN. This study explored the relationship between these features to gain insight into the pathophysiology of SSHTN. Plasma angiotensin II (AII) and renal interstitial AII (microdialysis technique) and the infiltration of macrophages, lymphocytes, and AII-positive cells were determined in SSHTN induced by 5 wk of a high-salt diet (HSD) after short-term infusion of AII in rats with (n = 10) and without (n = 11) treatment with mycophenolate mofetil (MMF) and in control rats fed a high- (n = 7) and normal (n = 11) salt diet. As in previous studies, MMF did not affect AII-associated hypertension but reduced the interstitial inflammation and the SSHTN in the post-AII-period. During the HSD period, the AII group untreated with MMF had mean +/- SD) low plasma (2.4 +/- 1.4 pg/ml) and high interstitial AII concentration (1,310 +/- 208 pg/ml); MMF treatment resulted in a significantly lower interstitial AII (454 +/- 128 pg/ml). Renal AII concentration and the number of tubulointerstitial AII-positive cells were correlated. Blood pressure correlated positively with interstitial AII and negatively with plasma AII, thus giving compelling evidence of the paramount role of the AII within the kidney in the AII-induced model of salt-driven hypertension.

Time-dependent changes in pulmonary vascular responses to acute hypoxia during and after cold exposure in rats

This study evaluated time-dependent alterations in pulmonary vascular reactivity to acute hypoxia and to the administration of angiotensin II (AT-II) during and after chronic exposure to cold using isolated perfused lung specimens from rats. Animals were exposed to a cold environment (3.5 (mean) +/- 1.0 (SD) degrees C) or to a normal temperature (24.0 +/- 1.0 degrees C) for 7 days. The isolated lungs were taken serially and pulmonary vascular responses to acute hypoxia and AT-II were examined. Both the pulmonary vascular responses to acute hypoxia and to AT-II were significantly reduced 9 h after the exposure to cold. The diminished vascular response to AT-II was restored to the pre-exposure level after 5 days of cold exposure and then sustained. On the other hand, the reduced response to acute hypoxia was sustained for the first 7 days during exposure to cold and then returned to the pre-exposure level during sustained exposure to cold. After removal from the 7 days of cold exposure, the pulmonary vascular response to acute hypoxia was immediately restored. Thus, during exposure to cold, pulmonary vascular response to acute hypoxia was more sustained than the AT-II-induced vasoconstriction. We concluded that cold exposure alters pulmonary vascular responses to acute hypoxia and AT-II in rats, but that the response to acute hypoxia is more sustained than that of AT-II.

Characterization of the angiotensin II (AngII) model of hypertension for inter‐laboratory investigation±

A recent report showed that in a well established model of salt-dependent hypertension—the AngII-induced model—arterial pressure (AP) did not increase in when AngII was given intravenously (iv) by osmotic minipumps and AP was measured by telemetry in rats on a normal salt diet (Hypertension 42: 798, 2003). To address this controversy we assessed the AP responses to AngII in rats on three levels of dietary salt (0.1%, 0.4% and 2.0% NaCl) in one laboratory, and determined the reproducibility of the model in four separate laboratories. AP was measured by telemetry for 7 control days and 14 days of AngII by osmotic minipump. Initial studies showed that minipumps were unreliable for iv AngII; therefore AngII was given subcutaneously (150 ng/kg/min). Control AP was similar between groups but the response to AngII was directly related to salt intake. By Day 14 of AngII AP increased 10 + 3 (n=6), 27 + 7 (n=6) and 44 + 9 (n=6) mmHg in 0.1%, 0.4% and 2.0% NaCl rats respectively in one laboratory. Moreover, the responses to AngII in rats consuming 0.4% and 2.0% NaCl diets were similar in 4 laboratories. By Day 14 of AngII AP increased 17 + 3 (n=27) and 33 + 4 mm Hg (n=26) for 0.4% and 2.0% NaCl rats respectively. We conclude that the AngII-induced model is salt-sensitive and is reproducible among different laboratories when AngII is infused subcutaneously by osmotic minipumps. NIH Grant HL 076312

Differential Regulation of Angiotensin II-induced Expression of Connective Tissue Growth Factor by Protein Kinase C Isoforms in the Myocardium

Protein kinase C (PKC) and angiotensin II (AngII) can regulate cardiac function in pathological conditions such as in diabetes or ischemic heart disease. We have reported that expression of connective tissue growth factor (CTGF) is increased in the myocardium of diabetic mice. Now we showed that the increase in CTGF expression in cardiac tissues of streptozotocin-induced diabetic rats was reversed by captopril and islet cell transplantation. Infusion of AngII in rats increased CTGF mRNA expression by 15-fold, which was completely inhibited by co-infusion with AT1 receptor antagonist, candesartan. Similarly, incubation of cultured cardiomyocytes with AngII increased CTGF mRNA expression by 2-fold, which was blocked by candesartan and a general PKC inhibitor, GF109203X. The role of PKC isoform-dependent action was further studied using adenoviral vector-mediated gene transfer of dominant negative (dn) PKC or wild type PKC isoforms. Expression of dnPKCalpha, -epsilon, and -zeta isoforms suppressed AngII-induced CTGF expression in cardiomyocytes. In contrast, expression of dominant negative PKCdelta significantly increased AngII-induced CTGF expression, whereas expression of wild type PKCdelta inhibited this induction. This inhibitory effect was further confirmed in the myocardium of transgenic mice with cardiomyocyte-specific overexpression of PKCdelta (deltaTg mice). Thus, AngII can regulate CTGF expression in cardiomyocytes through a PKC activation-mediated pathway in an isoform-selective manner both in physiological and diabetic states and may contribute to the development of cardiac fibrosis in diabetic cardiomyopathy.

Effects of atorvastatin on blood–brain barrier permeability during l-NAME hypertension followed by angiotensin-II in rats

Recent studies suggest that 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, can have direct effects on blood vessels beyond their cholesterol-lowering effects. We investigated the effects of atorvastatin on the functional and structural properties of blood–brain barrier (BBB) and the activity of astrocytes during the N ω-nitro- l-arginine methyl ester ( l-NAME) hypertension followed by angiotensin (ANG) II. We found that decreases in concentration of serum catalase and plasma nitric oxide (NO) induced by l-NAME were significantly ameliorated by atorvastatin, whereas l-NAME-induced serum malondialdehyde and cholesterol concentration increases were significantly reduced by atorvastatin. The content of Evans blue (EB) dye significantly increased in cerebellum, left cerebral cortex and diencephalon regions but atorvastatin markedly reduced the increased BBB permeability to EB in the brain regions of animals treated with l-NAME and l-NAME plus ANG II. Brain vessels of l-NAME-treated animals showed a considerable loss of immunoreactivity of tight junction proteins, zonula occludens (ZO)-1 and occludin. Immunoreactivity for ZO-1 and occludin increased in animals treated with atorvastatin and l-NAME plus atorvastatin. Glial fibrillary acidic protein (GFAP) immunoreactivity was seen in few astrocytes in the brain sections of l-NAME, but immunoreactivity for GFAP increased in l-NAME plus atorvastatin-treated animals. We suggest that long-term l-NAME treatment may affect BBB permeability through disruption of tight junction proteins, at least partly, via decreased NO concentration and increased oxidant capacity; the improvement of BBB integrity and astrocytic activity would be more closely associated with the action of atorvastatin favoring the increase in anti-oxidant capacity and expression of tight junction proteins and GFAP.

The AT2 receptor-mediated stimulation of adrenal catecholamine release may potentiate the AT1 receptor-mediated aldosterone secretagogue action of angiotensin-II in rats

The role played by AT1 and AT2 receptors in the mediation of angiotensin-II (ANG-II) aldosterone secretagogue action has been investigated in vitro using different types of rat adrenal preparations. ANG-II enhanced aldosterone secretion of dispersed zona glomerulosa (ZG) cells in a concentration-dependent manner (EC50, 3 × 10−10 M), and its effect was annulled by the AT1-receptor antagonist DuP753 and unaffected by the AT2-receptor antagonist PD123319. ANG-II was significantly more effective in stimulating aldosterone secretion when capsule-ZG and adrenal slices containing medullary chromaffin cells were used (EC50, 1 × 10−12 M and 7 × 10−12 M, respectively); moreover, both DuP753 and PD 123319 caused partial reversals (intense and moderate, respectively) of the responses to ANG-II, and when added together annulled them. The β-adrenoceptor antagonist l-alprenolol did not affect aldosterone response to ANG-II of dispersed ZG cells, but exerted a PD123319-like effect on the responses of capsule-ZG and adrenal slices In light of these findings we conclude that, when the integrity of adrenal tissue is preserved, ANG-II stimulates aldosterone secretion by activating both AT1 and AT2 receptors, the major role being played by AT1 receptors located on ZG cells. The activation of AT2 receptors probably elicits the local release of catecholamines, which in turn enhance aldosterone secretion in a paracrine manner acting through the β-adrenoceptors with which ZG cells are provided.

Potentiation by enalaprilat of fenoldopam-evoked natriuresis is due to blockade of intrarenal production of angiotensin-II in rats.

We have previously shown that the natriuretic response to DA-1 receptor agonist fenoldopam is markedly potentiated by angiotensin converting enzyme inhibitor captopril. Since inhibition of angiotensin converting enzyme can lead to decreased production of angiotensin-II and increased levels of kinins (e.g., bradykinin), it is likely that both of these mechanisms might be involved in this phenomenon. However, it is not known whether and to what degree the accumulation of kinins contributes to the overall potentiation of natriuretic response to fenoldopam seen during angiotensin converting enzyme inhibition. In the present study, we have examined the effect of angiotensin converting enzyme inhibitor enalaprilat and angiotensin-II receptor antagonist losartan as well as bradykinin-2 receptor antagonist HOE 140 on fenoldopam-induced natriuresis. Intravenous infusion of fenoldopam (1 microgram/kg/min) for 30 min produced significant increases in urine output and urinary sodium excretion without causing any changes in glomerular filtration rate, renal blood flow and mean arterial blood pressure, a phenomenon suggestive of a direct tubular site of action. In animals treated with either the angiotensin converting enzyme inhibitor enalaprilat or angiotensin-II receptor antagonist losartan, the diuretic and natriuretic effects of fenoldopam were potentiated to a similar degree. Whereas no significant changes in glomerular filtration rate occurred when fenoldopam alone was given to control rats, in animals treated with either enalaprilat or losartan, fenoldopam produced a modest but significant increase in glomerular filtration rate. In a separate group of animals, the effects of bradykinin-2 receptor antagonist HOE 140 on potentiation of fenoldopam-induced natriuresis by enalaprilat was examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal Proliferative and Phenotypic Changes in Rats With Two-Kidney, One-Clip Goldblatt Hypertension

Angiotensin II (AII) is a vasoconstrictive peptide with hypertrophic and mitogenic effects on many cell types. Previous studies have shown that in vivo administration of AII in rats results in proliferation of, and phenotypic changes in, many renal cell populations, but in doses also causing hypertension. Thus, it was not possible to differentiate nonhemodynamic from hypertensive effects of AII. Therefore, we studied rats with renin-dependent, AII-mediated hypertension (the two-kidney, one-clip Goldblatt model; mean systolic blood pressure 238 +/- 48 v 140 +/- 6 mm Hg in sham-operated controls). The unclipped kidneys, which were exposed to high blood pressure, developed significant glomerular and tubulointerstitial injury, tubulointerstitial cell proliferation, dense focal interstitial monocyte-macrophage influx, increased deposition of types I and IV collagen, as well as increased cellular expression of desmin and actin, in tubulointerstitial areas when examined at 11 weeks. In contrast, clipped kidneys, protected from hypertension but with high local renin expression, had minimal abnormalities. These studies suggest that in this model increased renin, and presumably AII, does not mediate significant proliferative or phenotypic changes in the kidney in the absence of hypertension at 11 weeks.

Role of the α 1-andα 2-adrenoceptors of the lateral hypothalamus in the dipsogenic response to central angiotensin II in rats

The present experiments were conducted to investigate the role of the α 1-andα 2-adrenergic receptors of the lateral hypothalamus (LH) on the drinking response elicited by intracerebroventricular (i.c.v) injections of carbachol and angiotensin II (AII) in rats. Clonidine (an α 2-adrenergic agonist) injected into the LH produced a dose-dependent reduction of the drinking responses elicited by i.c.v. administration of carbachol and AII. The α 1-adrenergic agonist phenylephrine injected into the LH reduced the dipsogenic response to i.c.v. AII, but not to carbachol. Injection of yohimbine (an α 2-adrenergic antagonist) and prazosin (an α 1-adrenergic antagonist) into the LH also reduced the water intake produced by i.c.v. injection of AII. Previous injection of α 1-orα 2-adrenergic antagonists into the LH increased the antidipsogenic effect of clonidine or phenylephrine injected into the same area on the water intake induced by i.c.v. AII. These results show that the α 1-andα 2-adrenergic receptors of the LH are involved in the control of drinking responses elicited by i.c.v. injection of AII in rats. They also show that clonidine, but not phenylephrine, suppresses the drinking induced by i.c.v. carbachol. The data suggest that the discharge of central α-adrenergic receptors has a dual (inhibitory and excitatory) effect on water intake induced by central AII.

Elevations in plasma angiotensin II with prolonged ethanol treatment in rats

Chronic alcohol consumption frequently leads to hypertension in humans. While previous reports have implicated the renin-angiotensin system as a potential mediator of this effect, plasma angiotensin II (AII) levels were either not measured or yielded negative results. The present investigation noted significant elevations in circulating AII in rats intubated daily with ethanol (4 g/kg) for 50 days. Animals administered ethanol only once evidenced AII concentrations equivalent with water intubated controls. Radioligand binding assay data indicated no differences in the number or affinity of Sar 1,Ile 8-AII binding sites in the thalamus, septum-anterior ventral third ventrical region or adrenal gland comparing those groups chronically treated with ethanol to water intubated controls. These results may support a role for the vasoconstrictive hormone AII in the etiology of alcohol-induced hypertension.