Abstract 413: Renal Cyclooxygenase-2 Expression And Hemodynamic Role During Angiotensin II-dependent Hypertension

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Alexis A Gonzalez ◽  
Torrance Green ◽  
Camille R Bourgeois ◽  
Christina Luffman ◽  
Minolfa C Prieto ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Late Phase ◽  
Renal Hemodynamics ◽  
Cyclooxygenase 2 ◽  
Kidney Cortex ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Cox 2

Intrarenal cyclooxygenase-2 (COX-2) activity is increased during activation of the renin-angiotensin-system (RAS) increasing synthesis of prostaglandin E2 (PGE2) and buffering the vasoconstrictor and antinatriuretic effects of angiotensin II (AngII). While AngII upregulates intrarenal COX-2 expression, it remains unclear if this occurs in a time-dependent manner, thereby impacting renal hemodynamics differently during the early and late phases of the development of high blood pressure in AngII-induced hypertension. Male Sprague-Dawley rats were infused with AngII (0.4 μg/min/kg). Systolic blood pressure (SBP), COX-2 expression and PGE2 tissue content and urinary excretion were evaluated at day 3, 7 and 14 of the AngII infusions. In acute studies we evaluated the effects of COX-2 inhibition at day 5-7 and day 14 on renal hemodynamic parameters. Chronic AngII infusions increased SBP from day 7 through 14: 162 ± 5 mmHg; and 198 ± 15 mmHg versus controls: 114 ± 10 mmHg; P<0.05. COX-2 mRNA and protein levels were high in kidney cortex only at day 3 (mRNA: 241 ± 56%, protein: 160 ± 21%, P<0.05 versus controls). Medullary COX-2 mRNA and protein were increased on days 3 (mRNA: 176 ± 20%, protein: 185 ± 32%, P<0.05 versus controls), 7 (mRNA: 189 ± 23%, protein: 158 ± 15%, P<0.05 versus controls) and 14 (mRNA: 148 ± 15%, protein: 135 ± 13%, P<0.05 versus controls). Urinary and medullary PGE2 increased by day 3 and remained elevated during days 7 and 14. COX-2 inhibition decreased GFR and renal blood flow in AngII infused rats during both the early and late phases. Interestingly, COX-2 inhibition decreased mean arterial blood pressure at day 14 of AngII-infusion (COX-2 inhibition: 124 ± 9 versus 140 ± 7 mmHg, P<0.05) but not during the early normotensive phase (COX-2 inhibition: 110 ± 4 versus 115± 4 mmHg, P=NS). These results indicate that enhanced medullary COX-2 expression and PGE2 production during both the early and late phases attenuates the effects of AngII on renal hemodynamics. However COX-2 inhibition at day 14 reduced blood pressure, suggesting that a vasoconstrictor COX-2 metabolite contributes to the hypertension during the late phase.

Effects of Manual Acupuncture with Sparrow Pecking on Muscle Blood Flow of Normal and Denervated Hindlimb in Rats

2008 ◽  
Vol 26 (3) ◽  
pp. 149-159 ◽  
Author(s):  
Hisashi Shinbara ◽  
Masamichi Okubo ◽  
Eiji Sumiya ◽  
Fumihiko Fukuda ◽  
Tadashi Yano ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Muscle Blood Flow ◽  
Dependent Manner ◽  
Manual Acupuncture ◽  
Sprague Dawley ◽  
Axon Reflex ◽  
Hindlimb Muscles ◽  
Arterial Blood ◽  
The Right

Introduction In clinical practice, it has been thought that acupuncture might serve to wash out pain-generating metabolic end-products by improving blood circulation in muscles. We investigated the effects of manual acupuncture (MA) on muscle blood flow (MBF) of normal and denervated hindlimbs in rats. Method Sprague-Dawley rats (n=100) anaesthetised with urethane (1.2g/kg ip) were used. Manual acupuncture with sparrow pecking (SP) at different doses (1, 10 or 30 pecks) was given to the right ventral hindlimb muscles (tibial anterior and extensor digitorum longus muscles) or the right dorsal hindlimb muscles (gastrocnemius, plantaris and soleus muscles). MBF with or without MA was measured using the radiolabelled microsphere technique. The blood pressure was recorded through the right common carotid artery until MBF measurement started. Denervation of hindlimb was conducted by cutting the sciatic and femoral nerves. Results In normal rats, significantly increased MBF after MA were observed only in muscles which were penetrated by an acupuncture needle. The size of the increase depended on the number of times of pecking and seemed to be sustained at least until 60 minutes after MA. However, the increase was observed after both acute and chronic denervation. On the other hand, the mean arterial blood pressure (MAP) did not change significantly before, during or after MA. Conclusion These results suggest that MA could increase muscle blood flow locally in a dose-dependent manner and that this increase may be caused by local vasodilators, as well as the axon reflex. A further study is needed to elucidate the mechanism.

Early co-expression of cyclooxygenase-2 and renin in the rat kidney cortex contributes to the development of NG-nitro-l-arginine methyl ester induced hypertension

2015 ◽  
Vol 93 (4) ◽  
pp. 299-308 ◽  
Author(s):  
Elizabeth Alejandrina Guzmán-Hernández ◽  
Rafael Villalobos-Molina ◽  
María Alicia Sánchez-Mendoza ◽  
Leonardo Del Valle-Mondragón ◽  
Gustavo Pastelín-Hernández ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Methyl Ester ◽  
Rat Kidney ◽  
Cyclooxygenase 2 ◽  
Kidney Cortex ◽  
Ang Ii ◽  
Rat Kidney Cortex ◽  
Induced Hypertension ◽  
Renin Mrna ◽  
Cox 2

We investigated the involvement of cyclooxygenase-2 (COX-2) and the renin–angiotensin system in NG-nitro-l-arginine methyl ester (l-NAME)-induced hypertension. Male Wistar rats were treated with l-NAME (75.0 mg·(kg body mass)−1·day−1, in their drinking water) for different durations (1–33 days). COX-2 and renin mRNA were measured using real-time PCR in the renal cortex, and prostanoids were assessed in the renal perfusate, whereas angiotensin II (Ang II) and Ang (1-7) were quantified in plasma. In some rats, nitric oxide synthase inhibition was carried out in conjunction with oral administration of captopril (30.0 mg·kg−1·day−1) or celecoxib (1.0 mg·kg−1·day−1) for 2 or 19 days. We found a parallel increase in renocortical COX-2 and renin mRNA starting at day 2 of treatment with l-NAME, and both peaked at 19–25 days. In addition, l-NAME increased renal 6-Keto-PGF1α (prostacyclin (PGI2) metabolite) and plasma Ang II from day 2, but reduced plasma Ang (1-7) at day 19. Captopril prevented the increase in blood pressure, which was associated with lower plasma Ang II and increased COX-2-derived 6-Keto-PGF1α at day 2 and plasma Ang (1-7) at day 19. Celecoxib partially prevented the increase in blood pressure; this effect was associated with a reduction in plasma Ang II. These findings indicate that renal COX-2 expression increased in parallel with renin expression, renal PGI2 synthesis, and plasma Ang II in l-NAME-induced hypertension.

Abstract P011: Novel Roles Of Global, Intestinal, And Kidney Proximal Tubule Sodium And Hydrogen Exchanger 3 In Angiotensin Ii-induced Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Jia L Zhuo ◽  
Liang Zhang ◽  
Ana Leite ◽  
Xiao C Li
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Pressor Response ◽  
Dependent Manner ◽  
Ang Ii ◽  
Wild Type ◽  
Salt Wasting ◽  
Arterial Blood ◽  
Induced Hypertension

The present study used global ( Nhe3 -/- ), kidney-selective (tg Nhe3 -/- ), and proximal tubule-specific Na + /H + exchanger 3 (NHE3)-deficient mice (PT- Nhe3 -/- ) to test the hypothesis that NHE3 is required for the full development of angiotensin II (Ang II)-induced hypertension in mice. Four groups of adult male, age-matched wild-type (WT), global Nhe3 -/- , kidney-selective tg Nhe3 -/- and proximal tubule-specific Nhe3 -/- mice were infused with: a) saline; b) Ang II (10 pmol/min, i.v.); Ang II via an osmotic minipump for 2 weeks (1.5 mg/kg/day, i.p.); or treated with Ang II and losartan concurrently for 2 weeks (20 mg/kg/day, p.o.). Under basal conditions, global Nhe3 -/- , kidney-selective tg Nhe3 -/- and proximal tubule-specific Nhe3 -/- mice all showed significantly lower systolic, diastolic, and mean arterial pressure than wild-type mice (~15 ± 3 mmHg, P <0.01). The hypotensive phenotype in both global Nhe3 -/- and kidney-selective tg Nhe3 -/- mice was associated with abnormal intestinal structures, diarrhea, increased 24 h fecal Na + excretion, and salt wasting ( P <0.01). By contrast, there were no differences in intestinal structures and fecal Na + excretion between wild-type and PT- Nhe3 -/- mice. PT- Nhe3 -/- mice showed significant diuretic and natriuretic responses compared with wild-type mice ( P <0.01). Acute infusion of Ang II markedly increased arterial blood pressure in a time-dependent manner in wild-type mice, as expected ( P <0.01), but the pressure response was attenuated in global Nhe3 -/- , kidney-selective tg Nhe3 -/- , and PT- Nhe3 -/- mice ( P <0.01). Furthermore, the chronic pressor response to 2-week Ang II infusion was also significantly attenuated in Nhe3 -/- , tgNhe3 -/- , and PT- Nhe3 -/- mice, compared with wild-type mice ( P <0.01). Finally, concurrent treatment with losartan completely blocked the acute and chronic pressor responses to Ang II in wild-type, Nhe3 -/- , tg Nhe3 -/- , and PT- Nhe3 -/- mice (p<0.01). Taken together, these data support the proof of concept that NHE3 in the small intestines and the proximal tubules of the kidney is required for maintaining basal blood pressure homeostasis and for the development of Ang II-induced hypertension. Supported by NIH grants, 2R01DK102429-03A1, 1R56HL130988-01, and 2R01DK067299-10A1.

Angiotensin II inhibition on blood pressure and renal hemodynamics in pregnant rats

1986 ◽  
Vol 250 (2) ◽  
pp. F308-F314 ◽  
Author(s):  
C. Baylis ◽  
R. C. Collins
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Renal Plasma Flow ◽  
Renal Hemodynamics ◽  
Urine Flow ◽  
Ang Ii ◽  
Pregnant Rats ◽  
Acute Surgery ◽  
Arterial Blood ◽  
Renal Vascular

Late-pregnant (18-20 days) and virgin rats were studied under anesthesia or while awake to investigate the effect of acute angiotensin II (ANG II) inhibition (with saralasin or captopril) on mean arterial blood pressure (AP) and renal hemodynamics. ANG II inhibition had no effect on AP in either anesthetized or awake virgin rats. Saralasin produced no effect on renal hemodynamics although with captopril small increases in renal plasma flow rate (RPF) and decreases in renal vascular resistance (RVR) occurred in virgins. In anesthetized pregnant rats, ANG II inhibition evoked marked decreases in AP. In some rats receiving saralasin, AP was only mildly depressed and RVR fell, leading to increases in glomerular filtration rate and RPF. In others, saralasin produced large decreases in AP, and indices of renal function became unmeasurable because of near cessation of urine flow. All late-pregnant anesthetized rats receiving captopril showed increased RPF irrespective of the magnitude of the fall in AP. In awake pregnant rats no effect on AP was seen with ANG II inhibition. Saralasin had no effect on renal hemodynamics although with captopril a small increase in RPF was observed. These data indicate that the stress of acute surgery and anesthesia produces a dependence of AP on ANG II in the pregnant but not the virgin rat. Under normal pregnant (awake) conditions, however, ANG II inhibition has no net effect on AP.

Cyclooxygenase-2 inhibition normalizes arterial blood pressure in CYP1A1-REN2 transgenic rats with inducible ANG II-dependent malignant hypertension

2006 ◽  
Vol 291 (3) ◽  
pp. F612-F618 ◽  
Author(s):  
Allison L. Opay ◽  
Cynthia R. Mouton ◽  
John J. Mullins ◽  
Kenneth D. Mitchell
Keyword(s):  
Blood Pressure ◽  
Renal Plasma Flow ◽  
Renal Hemodynamics ◽  
Malignant Hypertension ◽  
Hypertensive Rats ◽  
Transgenic Rats ◽  
Arterial Blood ◽  
Cox Inhibitor ◽  
Cox 2 ◽  
Cox 1

The present study was performed to determine the effects of cyclooxygenase (COX)-1 and COX-2 inhibition on blood pressure and renal hemodynamics in transgenic rats with inducible malignant hypertension [strain name: TGR(Cyp1a1Ren2)]. Male Cyp1a1-Ren2 rats ( n = 7) were fed a normal diet containing the aryl hydrocarbon, indole-3-carbinol (I3C; 0.3%), for 6–9 days to induce malignant hypertension. Mean arterial pressure (MAP) and renal hemodynamics were measured in pentobarbital sodium-anesthetized Cyp1a1-Ren2 rats during control conditions, following administration of the COX-2 inhibitor nimesulide (3 mg/kg iv), and following administration of the nonspecific COX inhibitor meclofenamate (5 mg/kg iv). Rats induced with I3C had higher MAP than noninduced rats ( n = 7; 188 ± 6 vs. 136 ± 4 mmHg, P < 0.01). There was no difference in renal plasma flow (RPF) or glomerular filtration rate (GFR) between induced and noninduced rats. Nimesulide elicited a larger decrease in MAP in hypertensive rats (188 ± 6 to 140 ± 8 mmHg, P < 0.01) than in normotensive rats (136 ± 4 to 113 ± 8 mmHg, P < 0.01). Additionally, nimesulide decreased GFR (0.9 ± 0.13 to 0.44 ± 0.05 ml·min−1·g−1, P < 0.05) and RPF (2.79 ± 0.27 to 1.35 ± 0.14 ml·min−1·g−1, P < 0.05) in hypertensive rats but did not alter GFR or RPF in normotensive rats. Meclofenamate further decreased MAP in hypertensive rats (to 115 ± 10 mmHg, P < 0.05) but did not decrease MAP in normotensive rats. Meclofenamate did not alter GFR or RPF in either group. These findings demonstrate that COX-1- and COX-2-derived prostanoids contribute importantly to the development of malignant hypertension in Cyp1a1-Ren2 transgenic rats. The data also indicate that COX-2-derived vasodilatory metabolites play an important role in the maintenance of RPF and GFR following induction of malignant hypertension in Cyp1a1-Ren2 transgenic rats.

Effect of phosphorus restriction on renal response to oral and intravenous protein loads in rats

1993 ◽  
Vol 264 (4) ◽  
pp. F752-F759 ◽  
Author(s):  
E. S. Kraus ◽  
L. Cheng ◽  
I. Sikorski ◽  
D. A. Spector
Keyword(s):  
Blood Pressure ◽  
Intravenous Infusion ◽  
Phosphorus Content ◽  
Renal Hemodynamics ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Dietary Phosphorus ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Renal Vascular

Dietary phosphorus restriction ameliorates renal injury in rats. This may be due to changes in renal hemodynamics, including those factors associated with protein-induced hyperfiltration. To test this, we measured inulin clearance (CIn), p-aminohippuric acid clearance (CPAH), mean arterial blood pressure, and renal vascular resistance (RVR) 1 h before and 100 min after either oral gavage of 2 g bovine serum albumin or intravenous infusion of 5% glycine in female Sprague-Dawley rats previously fed for 3-8 wk a 0.5% or a 0.1% phosphorus diet. Baseline CIn, CPAH, blood pressure, and RVR were similar. After albumin gavage, CIn rose 20% (P < 0.01) for the 0.5% phosphorus group but did not change for rats fed the 0.1% phosphorus diet. Other measured parameters, including plasma glucagon and renin activity, were not influenced by dietary phosphorus content. In contrast, during intravenous infusion of glycine, hyperfiltration was induced in phosphorus-restricted rats. Thus dietary phosphorus restriction ablates oral protein but not intravenous amino acid-induced hyperfiltration, suggesting a gut-mediated mechanism for the former. These data highlight the potential importance of dietary phosphorus as a mediator of renal hemodynamics.

Angiotensin II stimulates cyclooxygenase-2 mRNA expression in renal tissue from rats with kidney failure

2002 ◽  
Vol 282 (4) ◽  
pp. F592-F598 ◽  
Author(s):  
José Hernández ◽  
Horacio Astudillo ◽  
Bruno Escalante
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Systolic Blood Pressure ◽  
Kidney Failure ◽  
Renal Mass ◽  
Renal Tissue ◽  
Prostaglandin Synthesis ◽  
Cyclooxygenase 2 ◽  
Mass Reduction ◽  
Cox 2

We have shown increased cyclooxygenase-2 (COX-2) expression in rats with kidney failure. Increased angiotensin II concentration, hypertension, and renal mass reduction have been described during development of kidney failure. Thus we explored each of these mechanisms, because any one of them could be responsible for COX-2 induction. Kidney failure increased systolic blood pressure from 104 ± 5 to 138 ± 2 mmHg, urinary PGE2 from 74 ± 17 to 185 ± 25 ng/24 h, and COX-2 expression from 0.06 ± 0.04 to 0.17 ± 0.03 arbitraty units (AU). Treatment of the rats with ramipril or losartan prevented the increase in blood pressure, urinary PGE2, and COX-2 expression in the rats with kidney failure. Infusion of angiotensin II increased blood pressure from 101 ± 6 to 132 ± 6 mmHg, urinary PGE2 excretion from 62 ± 15 to 155 ± 17 ng/24 h, and COX-2 expression from 0.23 ± 0.01 to 1.6 ± 0.3 AU. When the angiotensin II-infused rats were treated with nitrendipine, blood pressure decreased from 132 ± 6 to 115 ± 2 mmHg, and urinary PGE2 excretion decreased from 152 ± 18 to 97 ± 12 ng/24 h, whereas COX-2 expression was 1.6 ± 0.7 and 1.7 ± 0.5 AU for rats with and without nitrendipine. Blood pressure of the rats with renal pole resection was similar to that in sham rats (97 ± 7 and 91 ± 4 mmHg, respectively), whereas COX-2 expression was increased in rats with renal pole resection, from 0.06 ± 0.04 to 0.12 ± 0.03 AU. We suggest that in kidney failure, the increase in angiotensin II concentration regulates COX-2 expression, thereby increasing prostaglandin synthesis, which contributes to the development of kidney failure.

Abstract P100: (Pro)renin Receptor (PRR) Mediates Renal Inflammation in Renovascular Hypertension

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Syed Siraj Ahmed Quadri ◽  
Caixia Li ◽  
Silas Culver ◽  
Helmy M Siragy
Keyword(s):  
Blood Pressure ◽  
Renovascular Hypertension ◽  
Blood Pressure Reduction ◽  
Left Renal Artery ◽  
Sprague Dawley ◽  
Renal Inflammation ◽  
Arterial Blood ◽  
Tnf Α ◽  
Protein Expressions ◽  
Cox 2

We hypothesized that PRR plays a role in renal inflammation in 2-kidney, 1-clip (2K1C) hypertension rat model. Male Sprague-Dawley rats were fed normal sodium diet. BP was obtained before and 28 days after left renal artery clipping. Renal expressions of PRR, TNF-α and COX-2 were assessed in sham and 2K1C rats with or without left renal interstitial administration of scramble shRNA or PRR shRNA. At baseline there were no significant differences in BP between different animal groups. Compared to sham, mean arterial blood pressure significantly increased in 2K1C (2K1C 131.8 ± 3.09 mmHg, vs. sham 108 ± 1.9 mmHg, P<0.0.05) at day 28 and was not influenced by scramble shRNA or PRR shRNA treatment. Compared to sham and contra lateral (non-clipped) kidney, there were increases in mRNA and protein expressions of PRR (90% and 45%, P<0.01), TNF-α (72% and 50%, P<0.05), COX-2 (72% and 39%, P<0.05) in the clipped kidney. These expressions were not influenced by scramble shRNA treatment. Compared to 2K1C (no treatment) and scramble shRNA, PRR shRNA treatment in the clipped kidney caused significant reductions in mRNA and protein expressions of PRR (60% and 54%, P<0.01, shown in figure below), TNF-α (54% and 51%, P<0.05), COX-2 (51% and 53%, P<0.05). We conclude that PRR mediates renal inflammation in renovascular hypertension independent of blood pressure reduction.

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