Enhanced renal expression of preproendothelin mRNA during chronic angiotensin II hypertension

2001 ◽  
Vol 280 (5) ◽  
pp. R1388-R1392 ◽  
Author(s):  
Barbara T. Alexander ◽  
Kathy L. Cockrell ◽  
A. Nicole Rinewalt ◽  
Jason N. Herrington ◽  
Joey P. Granger
Keyword(s):  
Arterial Pressure ◽  
Receptor Antagonist ◽  
Jugular Vein ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Endothelin System ◽  
Pressure Changes ◽  
Renal Expression

The purpose of this study was to determine the role of endothelin in mediating the renal hemodynamic and arterial pressure changes observed during chronic ANG II-induced hypertension. ANG II (50 ng · kg−1 · min−1) was chronically infused into the jugular vein by miniosmotic pump for 2 wk in male Sprague-Dawley rats with and without endothelin type A (ETA)-receptor antagonist ABT-627 (5 mg · kg−1 · day−1) pretreatment. Arterial pressure increased in ANG II rats compared with control rats (149 ± 5 vs. 121 ± 6 mmHg, P< 0.05, respectively). Renal expression of preproendothelin mRNA was increased by ∼50% in both the medulla and cortex of ANG II rats. The hypertensive effect of ANG II was completely abolished in rats pretreated with the ETA-receptor antagonist (114 ± 5 mmHg, P < 0.05). Glomerular filtration rate was decreased by 33% in ANG II rats, and this response was attenuated in rats pretreated with ETA-receptor antagonist. These data indicate that activation of the renal endothelin system by ANG II may play an important role in mediating chronic renal and hypertensive actions of ANG II.

scholarly journals Proinflammatory role of angiotensin II in a rat nephrosis model induced by adriamycin

2011 ◽  
Vol 12 (4) ◽  
pp. 404-412 ◽  
Author(s):  
Maydelin Muñoz ◽  
Jaimar Rincón ◽  
Adriana Pedreañez ◽  
Ninoska Viera ◽  
Juan P Hernández-Fonseca ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Macrophage Infiltration ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Group Water ◽  
Proinflammatory Role ◽  
Renal Expression ◽  
Losartan Treatment

Introduction: Nephrotic syndrome induced by adriamycin (ADR) is an experimental model of glomerulosclerosis in humans. The AT1 receptor for angiotensin II (Ang II) is involved in the renal expression of the nuclear factor-kappa B (NF-ΚB) during this nephrosis. NF-ΚB is a transcription factor for proinflammatory effects of Ang II; however, there is no information about the role of this receptor in the renal proinflammatory events in ADR nephrosis. Materials and methods: To determine the role of Ang II in ADR nephrosis, Sprague-Dawley rats were treated with ADR (6 mg/kg iv). One ADR group received oral losartan treatment (15 mg/kg gavage) 3 days before ADR injection and then daily for 4 weeks, and the other group water. Animals were sacrificed at week 4 and renal macrophage infiltration, ICAM-1, superoxide anion (O2-) and Ang II expressions were analysed by indirect immunofluorescence and histochemical techniques. Results: ADR rats showed increased expression of ICAM-1, Ang II, O2- and macrophage infiltration, events that were diminished by losartan treatment. Ang II expression remained unaltered after antagonist treatment. Proteinuria was reduced after 3 weeks of treatment. Conclusions: These data suggest that Ang II plays a role in the inflammatory events during ADR-induced nephrosis, probably mediated by AT1 receptors.

Cholecystokinin satiety involves CCKA receptors perfused by the superior pancreaticoduodenal artery

1998 ◽  
Vol 274 (5) ◽  
pp. R1390-R1396 ◽  
Author(s):  
James E. Cox
Keyword(s):  
Receptor Antagonist ◽  
Food Deprivation ◽  
Jugular Vein ◽  
Sucrose Intake ◽  
Sprague Dawley ◽  
Pancreaticoduodenal Artery ◽  
Cholecystokinin Octapeptide ◽  
Sprague Dawley Rats ◽  
Within Subjects ◽  
Ccka Receptors

Three experiments compared the potency of the type A cholecystokinin (CCKA)-receptor antagonist devazepide for increasing intake of 30% sucrose when injected into the superior pancreaticoduodenal (SPD) artery (SPD group) or jugular vein (IV group). In experiment 1, 15 min of sucrose intake in adult, male Sprague-Dawley rats after 6 h of food deprivation was increased by devazepide (20 μg/kg) administered into the SPD artery whether given alone or in conjunction with cholecystokinin octapeptide (CCK-8, 2 μg/kg ip). Devazepide had no effect in the IV group. In experiment 2, injection of 8, 20, and 50 μg/kg of devazepide into the SPD artery increased sucrose intake of nondeprived rats. Only the highest dose was effective in the IV group. On subsequent tests, administration of 1 μg/kg of CCK-8 significantly suppressed intake only in the SPD group. In experiment 3, nondeprived rats with SPD artery and jugular vein catheters were tested in a within-subjects design. Devazepide (20 μg/kg) increased sucrose intake after injection into the SPD artery, but not into the jugular vein. In experiment 4, intraduodenal devazepide (8, 20, and 50 μg/kg) had no effect. These results indicate that CCKA receptors within the SPD arterial bed mediate the satiating action of CCK, consistent with local action of duodenal CCK.

Role of endothelin ETB receptor activation in angiotensin II-induced hypertension: effects of salt intake

2001 ◽  
Vol 281 (5) ◽  
pp. H2218-H2225 ◽  
Author(s):  
Jennifer R. Ballew ◽  
Gregory D. Fink
Keyword(s):  
Arterial Pressure ◽  
Receptor Antagonist ◽  
Salt Intake ◽  
Receptor Activation ◽  
Salt Sensitivity ◽  
Male Rats ◽  
Ang Ii ◽  
High Salt Intake ◽  
Induced Hypertension

We showed recently that endothelin (ET)A receptors are involved in the salt sensitivity of ANG II-induced hypertension. The objective of this current study was to characterize the role of endothelin ETB receptor activation in the same model. Male rats on fixed normal (2 meq/day) or high (6 meq/day) salt intake received a continuous intravenous infusion of ANG II or salt only for 15 days. During the middle 5 days of the infusion period, rats were given either the selective ETB receptor antagonist A-192621 or the nonselective endothelin receptor antagonist A-182086 (both at 24 mg · kg−1 · day−1intra-arterially). Infusion of ANG II caused a greater rise in arterial pressure in rats on high-salt intake. The administration of A-192621 increased arterial pressure further in all rats. The chronic hypertensive effect of A-192621 was not significantly affected by salt intake or ANG II. The administration of A-182086 lowered arterial pressure chronically only in rats on normal salt intake receiving ANG II. Thus the salt sensitivity of ANG II-induced hypertension is not caused by changes in ETB receptor function.

Involvement of AT2 receptors at NRVL in tonic baroreflex suppression by endogenous angiotensins

1997 ◽  
Vol 272 (5) ◽  
pp. H2204-H2210 ◽  
Author(s):  
K. S. Lin ◽  
J. Y. Chan ◽  
S. H. Chan
Keyword(s):  
Suppressive Effect ◽  
Angiotensin Receptors ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Inhibitory Modulation ◽  
Sprague Dawley Rats ◽  
Peptide Antagonist ◽  
Endogenous Activity ◽  
At2 Receptors

We evaluated the role of endogenous angiotensin II and III (ANG II and ANG III) at the rostral nucleus reticularis ventrolateralis (NRVL) in the modulation of baroreceptor reflex (BRR) response and the subtype of angiotensin receptors involved in this process. Adult male Sprague-Dawley rats anesthetized and maintained with pentobarbital sodium were used. Exogenous application of ANG II or ANG III (10, 20, or 40 pmol) by bilateral microinjection into the NRVL significantly suppressed the BRR response to transient hypertension induced by phenylephrine (5 micrograms/kg i.v.). The suppressive effect of ANG II (20 pmol) was reversed by an equimolar dose (1.6 nmol) of its peptide antagonist, [Sar1, Ile8]ANG II, and the nonpeptide antagonists for AT1 and AT2 receptors, losartan and PD-123319, respectively. On the other hand, the inhibitory action of ANG III (20 pmol) was blunted by its peptide antagonist. [Ile7]ANG III or PD-123319, but not by losartan. Blocking the endogenous activity of the angiotensins by microinjection into the bilateral NRVL of [Sar1, Ile8]ANG II, [Ile7]ANG III, or PD-123319 elicited an appreciable enhancement of the BRR response, whereas losartan produced minimal effect. These results suggest that, under physiological conditions, both endogenous ANG II and ANG III may exert a tonic inhibitory modulation on the BRR response by acting selectively on the AT2 receptors at the NRVL.

Area postrema: essential for support of arterial pressure after hemorrhage in rats

1990 ◽  
Vol 258 (6) ◽  
pp. R1472-R1478 ◽  
Author(s):  
K. M. Skoog ◽  
M. L. Blair ◽  
C. D. Sladek ◽  
W. M. Williams ◽  
M. L. Mangiapane
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Data Acquisition ◽  
Area Postrema ◽  
Plasma Renin ◽  
Base Line ◽  
Sprague Dawley ◽  
Time Period ◽  
Sprague Dawley Rats

Previous studies have indicated that the area postrema (AP) of the rat is necessary for the development of chronic angiotensin-dependent hypertension. The present study assesses the role of the AP in the maintenance of arterial pressure during hemorrhage. Sprague-Dawley rats were given sham or AP lesions 1 wk before the experiment. They were instrumented with femoral arterial and venous catheters 2 days before the experiment. On the day of the experiment, base-line mean arterial pressure (MAP) was measured for 1 h before hemorrhage. During the following 45 min, each rat was subjected to one 7-ml/kg hemorrhage every 15 min for a total of three hemorrhages. MAP was monitored by computerized data acquisition. As shown previously, MAP was slightly but significantly lower in AP-lesion rats compared with sham-lesion rats before the hemorrhage procedure. In AP-lesion rats, hemorrhage resulted in a significantly greater fall in arterial pressure than in sham-lesion rats. In spite of larger drops in pressure in AP-lesion rats, hemorrhage caused equivalent increases in plasma renin and vasopressin in both groups. In AP-lesion rats compared with sham-lesion rats, significant bradycardia was present before hemorrhage. Hemorrhage caused bradycardia in both sham- and AP-lesion rats relative to the prehemorrhage heart rates, but AP-lesion rats showed greater bradycardia than did sham-lesion rats during every time period. We conclude that the AP may play an important role in the defense of arterial pressure against hemorrhage.

scholarly journals COX-2-independent activation of renal (pro)renin receptor contributes to DOCA-salt hypertension in rats

2020 ◽  
Vol 319 (4) ◽  
pp. F647-F653
Author(s):  
Fei Wang ◽  
Ying Sun ◽  
Renfei Luo ◽  
Xiaohan Lu ◽  
Baoxue Yang ◽  
...  
Keyword(s):  
Renal Medulla ◽  
Immunoblot Analysis ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Salt Treatment ◽  
Sprague Dawley Rats ◽  
Salt Hypertension ◽  
Cox 2 ◽  
Universal Mechanism

It has been shown that cyclooxygenase (COX)-2-dependent activation of renal (pro)renin receptor (PRR) contributes to angiotensin II (ANG II)-induced hypertension. However, less is known about the involvement of this mechanism in ANG II-independent hypertension. The goal of the present study was to test whether or not COX-2-dependent upregulation of PRR serves as a universal mechanism contributing to ANG II-dependent and -independent hypertension. Here, we examined the association between renal COX-2 and PRR during deoxycorticosterone acetate (DOCA)-salt hypertension in rats. By immunoblot analysis and immunofluorescence, renal protein expression of PRR was remarkably upregulated by DOCA-salt treatment. Surprisingly, this upregulation of renal PRR expression was unaffected by a COX-2 inhibitor, celecoxib. To address the role of renal PRR to the pathogenesis of DOCA-salt hypertension, a decoy PRR inhibitor, PRO20, was infused to the renal medulla of uninephrectomized Sprague-Dawley rats for 14 days. Radiotelemetry demonstrated effective attenuation of DOCA-salt hypertension by intramedullary infusion of a PRR inhibitor, PRO20. In parallel, DOCA-salt-induced hypertrophy in the heart and kidney as well as proteinuria were improved, accompanied with blunted polydipsia and polyuria. In contrast, intravenous infusion of PRO20 was less effective in attenuating DOCA-salt hypertension and cardiorenal injury. Together, these results suggest that COX-2-independent activation of renal PRR contributes to DOCA-salt hypertension.

scholarly journals The Intermediation Role of Central Cyclooxygenase Products TXA2, PGF2α, PGE, and PGD in Orexin-evoked Cardiovascular Effects

2021 ◽  
Author(s):  
Burçin Altınbaş ◽  
Gökcen Guvenc Bayram ◽  
Murat Yalcin
Keyword(s):  
Receptor Antagonist ◽  
Cardiovascular Effects ◽  
Cardiovascular Responses ◽  
Mediating Effects ◽  
Sprague Dawley ◽  
Synthesis Inhibitor ◽  
Sprague Dawley Rats ◽  
Arachidonic Acid Metabolites ◽  
Acid Metabolites

Abstract Centrally injected some prostaglandins (PG) and orexin (OX) produce similar cardiovascular responses. We have recently reported that both central cyclooxygenase (COX) and central lipoxygenase (LOX) enzymes mediate the cardiovascular effects of OX. In the current study, we aimed to investigate the mediating effects of thromboxane (TX) A2, PGD, PGE, and PGF2a, as COX pathway subproducts known to be active in cardiovascular control, on cardiovascular responses elicited by OX. Intracerebroventricular (i.c.v.) injection of OX increased cardiovascular levels in normotensive male Sprague Dawley rats. Moreover, central pretreatment with the TXA2 synthesis inhibitor furegrelate, PGF2α receptor antagonist, PGF2α-dimethylamine, PGE, and PGD receptor antagonist AH6809 partially attenuated the centrally administered OX -induced pressor and tachycardic cardiovascular responses in rats. In conclusion, our results show that i.c.v. injection of OX increases blood pressure and heart rate. Moreover, TXA2, PGF2α, PGE, and PGD mediate, at least in part, the centrally applied OX -evoked pressor and tachycardic responses. The results suggest that centrally injected OX -evoked pressor and tachycardia responses may also be mediated by arachidonic acid metabolites other than TXA2, PGF2α, PGE, and PGD.

scholarly journals Acute and chronic angiotensin-(1–7) restores vasodilation and reduces oxidative stress in mesenteric arteries of salt-fed rats

2011 ◽  
Vol 301 (4) ◽  
pp. H1341-H1352 ◽  
Author(s):  
Gábor Raffai ◽  
Matthew J. Durand ◽  
Julian H. Lombard
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Oxidant Stress ◽  
Chronic Administration ◽  
Mesenteric Arteries ◽  
Ang Ii ◽  
Vascular Relaxation ◽  
Sprague Dawley ◽  
Mas Receptor ◽  
Sprague Dawley Rats

This study determined the effect of ANG-(1–7) on salt-induced suppression of endothelium-dependent vasodilatation in the mesenteric arteries of male Sprague-Dawley rats. Chronic intravenous infusion of ANG-(1–7), oral administration of the nonpeptide mas receptor agonist AVE-0991, and acute preincubation of the arteries with ANG-(1–7) and AVE-0991 all restored vasodilator responses to both ACh and histamine that were absent in the arteries of rats fed a high-salt (4% NaCl) diet. The protective effects of ANG-(1–7) and AVE-0991 were inhibited by acute or chronic administration of the mas receptor antagonist A-779, the ANG II type 2 (AT2) receptor blocker PD-123319, or N-nitro-l-arginine methyl ester, but not the ANG II type 1 receptor antagonist losartan. Preincubation with the antioxidant tempol or the nitric oxide (NO) donor diethylenetriamine NONOate and acute and chronic administration of the AT2 receptor agonist CGP-42112 mimicked the protective effect of ANG-(1–7) to restore vascular relaxation. Acute preincubation with ANG-(1–7) and chronic infusion of ANG-(1–7) ameliorated the elevated superoxide levels in rats fed a high-salt diet, but the expression of Cu/Zn SOD and Mn SOD enzyme proteins in the vessel wall was unaffected by ANG-(1–7) infusion. These results indicate that both acute and chronic systemic administration of ANG-(1–7) or AVE-0991 restore endothelium-dependent vascular relaxation in salt-fed Sprague-Dawley rats by reducing vascular oxidant stress and enhancing NO availability via mas and AT2 receptors. These findings suggest a therapeutic potential for mas/AT2 receptor activation in preventing the vascular oxidant stress and endothelial dysfunction associated with elevated dietary salt intake.

Glucagon-like peptide (GLP-1) is involved in the central modulation of fecal output in rats

2000 ◽  
Vol 278 (6) ◽  
pp. G924-G929 ◽  
Author(s):  
M. Ali Gülpinar ◽  
Ayhan Bozkurt ◽  
Tamer Coşkun ◽  
Nefise B. Ulusoy ◽  
Berrak Ç. Yeǧen
Keyword(s):  
Receptor Antagonist ◽  
Restraint Stress ◽  
Colonic Motility ◽  
Sprague Dawley ◽  
Fecal Output ◽  
Sprague Dawley Rats ◽  
Ketamine Anesthesia ◽  
Stereotaxic Instrument ◽  
Glucagon Like Peptide

In addition to its insulinotropic action, exogenously administered glucagon-like peptide (GLP-1) inhibits gastropancreatic motility and secretion via central pathways. The aims of the present study were to evaluate the effects of exogenous GLP-1-(7–36) amide on fecal output and to investigate the role of endogenous GLP-1 on stress-induced colonic activity. With the use of a stereotaxic instrument, adult male Sprague-Dawley rats weighing 200–250 g were fitted with stainless steel cerebroventricular guide cannulas under ketamine anesthesia. A group of rats were placed in Bollman-type cages to induce restraint stress. Fecal output monitored for 2 h was increased significantly by intracerebroventricular GLP-1 to 500, 1,000, and 3,000 pmol/rat ( P < 0.05–0.01), whereas intraperitoneal GLP-1 had no effect. Intracerebroventricular administration of the GLP-1 receptor antagonist exendin-(9–39) (10 nmol/rat) reversed the increases induced by GLP-1 (500 pmol/rat; P < 0.01). Similar results were also observed with the injection of corticotropin-releasing factor receptor antagonist astressin (10 μg/rat icv). The significant increase in fecal pellet output induced by restraint stress was also decreased by both intracerebroventricular exendin (10 nmol/rat) and astressin (10 μg/rat; P < 0.01–0.001). These results suggest that GLP-1 participates in the central, but not peripheral, regulation of colonic motility via its own receptor and that GLP-1 is likely to be a candidate brain-gut peptide that acts as a physiological modulator of stress-induced colonic motility.

Superoxide mediates acute renal vasoconstriction produced by angiotensin II and catecholamines by a mechanism independent of nitric oxide

2007 ◽  
Vol 292 (1) ◽  
pp. H83-H92 ◽  
Author(s):  
Armin Just ◽  
Andrea J. M. Olson ◽  
Christina L. Whitten ◽  
William J. Arendshorst
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Vascular Remodeling ◽  
Oxygen Species ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Adrenergic Agonist ◽  
Renal Vasoconstriction ◽  
Sprague Dawley Rats

NAD(P)H oxidases (NOX) and reactive oxygen species (ROS) are involved in vasoconstriction and vascular remodeling during hypertension produced by chronic angiotensin II (ANG II) infusion. These effects are thought to be mediated largely through superoxide anion (O2−) scavenging of nitric oxide (NO). Little is known about the role of ROS in acute vasoconstrictor responses to agonists. We investigated renal blood flow (RBF) reactivity to ANG II (4 ng), norepinephrine (NE, 20 ng), and α1-adrenergic agonist phenylephrine (PE, 200 ng) injected into the renal artery (ira) of anesthetized Sprague-Dawley rats. The NOX inhibitor apocynin (1–4 mg·kg−1·min−1 ira, 2 min) or the superoxide dismutase mimetic Tempol (1.5–5 mg·kg−1·min−1 ira, 2 min) rapidly increased resting RBF by 8 ± 1% ( P < 0.001) or 3 ± 1% ( P < 0.05), respectively. During NO synthase (NOS) inhibition ( Nω-nitro-l-arginine methyl ester, 25 mg/kg iv), the vasodilation tended to increase (apocynin 13 ± 4%, Tempol 10 ± 1%). During control conditions, both ANG II and NE reduced RBF by 24 ± 4%. Apocynin dose dependently reduced the constriction by up to 44% ( P < 0.05). Similarly, Tempol blocked the acute actions of ANG II and NE by up to 48–49% ( P < 0.05). In other animals, apocynin (4 mg·kg−1·min−1 ira) attenuated vasoconstriction to ANG II, NE, and PE by 46–62% ( P < 0.01). During NOS inhibition, apocynin reduced the reactivity to ANG II and NE by 60–72% ( P < 0.01), and Tempol reduced it by 58–66% ( P < 0.001). We conclude that NOX-derived ROS substantially contribute to basal RBF as well as to signaling of acute renal vasoconstrictor responses to ANG II, NE, and PE in normal rats. These effects are due to O2− rather than H2O2, occur rapidly, and are independent of scavenging of NO.

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