scholarly journals Role of 20-HETE in the impaired myogenic and TGF responses of the Af-Art of Dahl salt-sensitive rats

2014 ◽  
Vol 307 (5) ◽  
pp. F509-F515 ◽  
Author(s):  
Ying Ge ◽  
Sydney R. Murphy ◽  
Fan Fan ◽  
Jan Michael Williams ◽  
John R. Falck ◽  
...  
Keyword(s):  
Genetic Background ◽  
Receptor Agonist ◽  
Perfusion Pressure ◽  
Tubuloglomerular Feedback ◽  
Brown Norway ◽  
Synthesis Inhibitor ◽  
Renal Vasculature ◽  
Luminal Diameter

The present study examined whether 20-HETE production is reduced in the renal vasculature and whether this impairs myogenic or tubuloglomerular feedback (TGF) responses of the afferent arteriole (Af-Art). The production of 20-HETE was 73% lower in renal microvessels of Dahl salt-sensitive rats (SS) rats than in SS.5BN rats, in which chromosome 5 from the Brown Norway (BN) rat containing the CYP4A genes was transferred into the SS genetic background. The luminal diameter of the Af-Art decreased by 14.7 ± 1.5% in SS.5BN rats when the perfusion pressure was increased from 60 to 120 mmHg, but it remained unaltered in SS rats. Administration of an adenosine type 1 receptor agonist (CCPA, 1 μM) reduced the diameter of the Af-Art in the SS.5BN rats by 44 ± 2%, whereas the diameter of the Af-Art of SS rats was unaltered. Autoregulation of renal blood flow (RBF) and glomerular capillary pressure (PGC) was significantly impaired in SS rats but was intact in SS.5BN rats. Administration of a 20-HETE synthesis inhibitor, HET0016 (1 μM), completely blocked the myogenic and adenosine responses in the Af-Art and autoregulation of RBF and PGC in SS.5BN rats, but it had no effect in SS rats. These data indicate that a deficiency in the formation of 20-HETE in renal microvessels impairs the reactivity of the Af-Art of SS rats and likely contributes to the development of hypertension induced renal injury.

Abstract 36: Deficiency in the Production of 20-HETE Contributes to Impaired Myogenic and TGF Responses in the Afferent Arteriole of Dahl S Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Ying Ge ◽  
Fan Fan ◽  
Sydney R Murphy ◽  
Jan Michael Williams ◽  
Ruisheng Liu ◽  
...  
Keyword(s):  
Renal Injury ◽  
Tubuloglomerular Feedback ◽  
Brown Norway ◽  
Sodium Reabsorption ◽  
Thick Ascending Limb ◽  
Afferent Arteriole ◽  
Synthesis Inhibitor ◽  
Renal Vasculature ◽  
Luminal Diameter ◽  
Consomic Strain

Previous studies have indicated that a deficiency in the formation of 20-HETE in the proximal tubule and thick ascending limb of Henle in Dahl S rats increases sodium reabsorption and contributes to the development of hypertension. The present study examined whether the lack of 20-HETE production in the renal vasculature contributes to the progression of renal injury by altering the myogenic or tubuloglomerular feedback (TGF) response of the afferent arteriole (Af-Art). The production of 20-HETE was significantly lower by 54% in renal microvessels isolated from the kidneys of Dahl S rats versus that seen than in SS.5BN consomic strain in which chromosome 5 from the Brown Norway (BN) rat containing the CYP4A genes responsible for the formation of 20-HETE was transferred into the Dahl S genetic background. The luminal diameter of the Af-Art decreased by 14.7± 1.5% (from 20.5 ± 0.7 to 17.5 ± 0.8 μm, n=6) in SS.5BN rats whereas the diameter of the Af-Art remained unaltered in Dahl S rats (from 20.1 ± 0.6 to 21.7 ± 0.6 μm, n=7) when the perfusion pressure was increased from 60 mmHg to 120 mmHg. In other experiments, adenosine (1 μM) reduced the diameter of the Af-Art in the SS.5BN rats by 15±0.7% (from 20.1 ±0.4 to 17.1 ± 0.9 μm, n=3) whereas the Af-Art of Dahl S rats was unaltered. However, administration of a 20-HETE synthesis inhibitor, HET0016 (1 μM, n=6), or a selective 20-HETE antagonist, 6, 15-20-HEDE (10 μM, n=6) completely blocked the myogenic and adenosine responses in the Af-Art of SS.5BN rats but it had no effect in Dahl S rats. Administration of a 20-HETE agonist, 5, 14-20-HEDE (1 μM) restored the myogenic response (from 20.7 ± 0.7 to 17.6 ± 0.6 μm, n=7) and vasoconstrictor response to adenosine in the Af-Art of Dahl S rats. These studies confirm the key role of 20-HETE in modulating the responsiveness of the Af-Art and indicate that a deficiency in the formation of 20-HETE in renal microvessels contributes to the marked susceptibility of Dahl S rats to develop hypertension induced renal injury.

Effects of calcitonin gene-related peptide on vascular resistance in rats: role of sex steroids

1999 ◽  
Vol 276 (6) ◽  
pp. H2063-H2068 ◽  
Author(s):  
Michelle Grewal ◽  
Janis Cuevas ◽  
Gautam Chaudhuri ◽  
Lauren Nathan
Keyword(s):  
Sex Steroids ◽  
Perfusion Pressure ◽  
Pressor Response ◽  
Calcitonin Gene Related Peptide ◽  
Ovariectomized Rats ◽  
Synthesis Inhibitor ◽  
Pregnant Rats ◽  
Related Peptide ◽  
Calcitonin Gene

It has been demonstrated in reflex-intact animals that the sensitivity to calcitonin gene-related peptide (CGRP) is increased during pregnancy and that this action is mediated by sex steroids but not by nitric oxide (NO). We assessed the effects of CGRP in the following groups of anesthetized ganglion-blocked rats: 1) pregnant, 2) ovariectomized, and 3) ovariectomized and treated with estradiol and progesterone. Changes in mean arterial pressure (MAP) were assessed after the administration of varying doses of CGRP. Decreases in MAP after CGRP administration were significantly greater in pregnant rats and ovariectomized rats administered sex steroids than in ovariectomized controls. The CGRP antagonist CGRP8–37 produced a pressor response of similar magnitude in both pregnant and ovariectomized rats. We also assessed the effects of CGRP and the modulating role of NO in the isolated uterine vascular bed preparation. CGRP reduced perfusion pressure to a greater degree in ovariectomized animals treated with sex steroids than in ovariectomized animals. This response was attenuated by pretreatment with an NO synthesis inhibitor. CGRP8–37 produced a similar increase in perfusion pressure in both groups. We conclude that 1) the increased vascular sensitivity observed during pregnancy or after treatment with sex steroids is in part mediated by NO, and 2) CGRP8–37 has a vasoconstrictor action of its own.

scholarly journals Unexpected effect of angiotensin AT1 receptor blockade on tubuloglomerular feedback in early subtotal nephrectomy

2009 ◽  
Vol 296 (5) ◽  
pp. F1158-F1165 ◽  
Author(s):  
Prabhleen Singh ◽  
Aihua Deng ◽  
Roland C. Blantz ◽  
Scott C. Thomson
Keyword(s):  
Tubuloglomerular Feedback ◽  
Male Rats ◽  
Ang Ii ◽  
Subtotal Nephrectomy ◽  
Henle's Loop ◽  
Salutary Effect ◽  
Single Nephron ◽  
Distal Delivery

After subtotal nephrectomy (STN), the remaining nephrons engage in hyperfiltration, which may be facilitated by a reduced sensitivity of the tubuloglomerular feedback (TGF) response to increased distal delivery. However, a muted TGF response would contradict the notion of remnant kidney as a prototype of angiotensin II (ANG II) excess, since ANG II normally sensitizes the TGF response and stimulates proximal reabsorption. We examined the role of ANG II as a modulator of TGF and proximal reabsorption in 7 days after STN in male rats. Single-nephron glomerular filtration rate (SNGFR) and proximal reabsorption ( Jprox) were measured in late proximal collections while perfusing Henle's loop for minimal and maximal TGF stimulation in rats treated with the angiotensin type 1 (AT1) receptor blocker losartan or placebo in drinking water for 7 days. Perfusion of Henle's loop yielded a robust TGF response in sham-operated rats. In STN, the feedback responses were highly variable and nil, on average. Paradoxical TGF responses to augmented late proximal flow were confirmed in SNGFR measurements from the early distal nephron. Chronic losartan treatment normalized the average TGF response without reducing the variability. Jprox was subtly affected by chronic losartan in sham surgery or STN, after controlling for differences in SNGFR. However, when administered acutely into the early S1 segment, losartan potently suppressed Jprox in STN and sham-operated rats alike. Chronic losartan stabilizes the TGF system in remnant kidneys. This cannot be explained by currently known actions of AT1 receptors but is commensurate with a salutary effect of an intact TGF system on dynamic autoregulation of intraglomerular flow and pressure.

Renal hemodynamic response to l-arginine in uncomplicated, type 1 diabetes mellitus: the role of buffering anions and tubuloglomerular feedback

2012 ◽  
Vol 303 (5) ◽  
pp. F648-F658 ◽  
Author(s):  
Alberto Montanari ◽  
Almerina Biggi ◽  
Aderville Cabassi ◽  
Irene Pelloni ◽  
Filippo Pigazzani ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Filtration Rate ◽  
Critical Role ◽  
Hemodynamic Response ◽  
Tubuloglomerular Feedback ◽  
Critical Determinant ◽  
Renal Hemodynamic ◽  
Type 1 Dm

According to the “tubulocentric” hypothesis of the glomerular hyperfiltration of diabetes mellitus (DM), tubuloglomerular feedback (TGF) is the critical determinant of the related renal hemodynamic dysfunction. To examine the role of TGF in human type 1 DM, 12 salt-replete healthy (C) and 11 uncomplicated DM individuals underwent measurements of glomerular filtration rate (GFR), renal blood flow (RBF), and lithium-derived absolute “distal” sodium delivery (DDNa). Measurements were made during two 3-h infusions of 0.012 mmol·kg−1·min−1 l-arginine (ARG) buffered with either equimolar HCl (ARG.HCl) or citric acid (ARG.CITR). Our hypothesis was that changes in TGF signaling would be directionally opposite ARG.HCl vs. ARG.CITR according to the effects of the ARG-buffering anion on DDNa. Similar changes in C and DM followed ARG.CITR, with declines in DDNa (−0.26 ± 0.07 mmol/min C vs. −0.31 ± 0.07 mmol/min DM) and increases in RBF (+299 ± 25 vs. +319 ± 29 ml·min−1·1.73 m−2) and GFR (+6.6 ± 0.8 vs. +11.6 ± 1.2 ml·min−1·1.73 m−2). In contrast, with ARG.HCl, DDNa rose in both groups ( P = 0.001), but the response was 73% greater in DM (+1.50 ± 0.15 mmol/min C vs. +2.59 ± 0.22 mmol/min DM, P = 0.001). RBF also increased ( P = 0.001, +219 ± 20 ml·min−1·1.73 m−2 C, +105 ± 14 DM), but ΔRBF after ARG.HCl was lower vs. ARG.CITR in both groups ( P = 0.001). After ARG.HCl, ΔRBF also was 50% lower in DM vs. C ( P = 0.001) and GFR, unchanged in C, declined in DM (−7.4 ± 0.9 ml·min−1·1.73 m−2, P = 0.02 vs. C). After ARG.HCl, unlike ARG.CITR, DDNa increased in C and DM, associated with less ΔRBF and ΔGFR vs. ARG.CITR. This suggests that the renal hemodynamic response to ARG is influenced substantially by the opposite actions of HCl vs. CITR on DDNa and TGF. In DM, the association of ARG.HCl-induced exaggerated ΔDDNa, blunted ΔRBF, and the decline in GFR vs. C shows an enhanced TGF dependence of renal vasodilatation to ARG, in agreement with a critical role of TGF in DM-related renal hemodynamic dysfunction.

Role of Additional GLP-1 Receptor Agonist to Insulin Regimen in Type 1 Diabetes among Pediatric Age

2021 ◽  
Vol 10 (3) ◽  
pp. 141-146
Author(s):  
Hussain Abdrabalrasool Alturaifi ◽  
Nof Tarq Alzayyat ◽  
Majed Shuraya Mohammed Alshahrani ◽  
Mujtaba Matar M Alnakhli ◽  
Abdulrahman Almuataz W Ezzi ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Receptor Agonist ◽  
Insulin Regimen ◽  
Pediatric Age

Abstract 222: Upregulation Of Cyp4a1 Gene Expression Restores The Impaired Myogenic Response And Autoregulation Of Cerebral Blood Flow In Dahl Salt Sensitive Rats

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Fan Fan ◽  
Mallikarjuna R Pabbidi ◽  
Aron M Geurts ◽  
Howard Jacob ◽  
Richard J Roman
Keyword(s):  
Vascular Tone ◽  
Perfusion Pressure ◽  
Cerebral Arteries ◽  
Organ Damage ◽  
Brown Norway ◽  
Myogenic Response ◽  
Transgenic Rats ◽  
Outer Medulla ◽  
Luminal Diameter ◽  
Middle Cerebral Arteries

We have reported that a reduction in the expression of CYP4A and the production of 20-HETE in the renal outer medulla contributes to development of hypertension in Dahl salt sensitive (SS) rats. The present study examined whether 20-HETE production is also reduced in the vasculature and if a deficiency in the formation of 20-HETE in the vasculature alters vascular tone and promotes end organ damage. The production of 20-HETE, the myogenic response of middle cerebral arteries (MCA) and autoregulation of cerebral blow flow (CBF) was compared in SS, CYP4A1 transgenic SS rats and SS.5BN consomic rats in which chromosome 5 from Brown Norway (BN) was transferred into the SS genetic background. 20-HETE production was 6-fold higher in cerebral arteries obtained from CYP4A1 transgenic (n=25) and SS.5BN (n=4)rats than in SS (n=17) rats 0.77 ± 0.08 versus 0.12 ± 0.03 pmol/mg/min). The luminal diameter of MCA decreased to 70 ± 3 % in CYP4A1 transgenic rats and to 65 ± 6 in SS.5BN when perfusion pressure was increased from 40 to 140 mmHg, whereas it remained unaltered in SS rats. Administration of the inhibitor of the synthesis of 20-HETE, HET0016 (10 uM), abolished the myogenic response in MCA of CYP4A1 transgenic and SS.5BN rats but had no effect in SS rats. CBF was poorly autoregulated and increased by 49 ± 6% in SS rats as MAP was increased by 60% from 100 to 160 mmHg. In contrast, CBF was only increased by 26 ± 5% and in SS.5BN rats and by 19 ± 2% in CYP4A1 transgenic rats when MAP was increased in the same range. These results indicate that a genetic deficiency of 20-HETE contributes to an impaired myogenic response in autoregulation of CBF in SS rats which may contribute to vascular remodeling, stroke and dementia following the onset of hypertension.

Role of herpes simplex virus type 1 (HSV-1) in the pathogenesis of peptic ulcer disease

2001 ◽  
Vol 120 (5) ◽  
pp. A136-A137
Author(s):  
K TSAMAKIDES ◽  
E PANOTOPOULOU ◽  
D DIMITROULOPOULOS ◽  
M CHRISTOPOULO ◽  
D XINOPOULOS ◽  
...  
Keyword(s):  
Peptic Ulcer ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Peptic Ulcer Disease ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Ulcer Disease ◽  
Simplex Virus
Sign in / Sign up

Export Citation Format

Share Document