Nitric Oxide Affects Angiotensin II Pressor Response: Possible Mechanism of Attenuated Pressor Response during Pregnancy and Etiology of Pregnancy-Induced Hypertension

2000 ◽  
Vol 49 (2) ◽  
pp. 84-87 ◽  
Author(s):  
Takahiro Maeda ◽  
Toshihiro Yoshimura ◽  
Akihiro Ohshige ◽  
Hideki Koyama ◽  
Masaharu Ito ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Pressor Response ◽  
Pregnancy Induced Hypertension ◽  
Induced Hypertension

Role of nitric oxide resistance in erythropoietin-induced hypertension in rats with chronic renal failure

1996 ◽  
Vol 271 (1) ◽  
pp. E113-E122 ◽  
Author(s):  
N. D. Vaziri ◽  
X. J. Zhou ◽  
F. Naqvi ◽  
J. Smith ◽  
F. Oveisi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Failure ◽  
Chronic Renal Failure ◽  
Angiotensin Ii ◽  
Pressor Response ◽  
Magnesium Concentration ◽  
Induced Hypertension ◽  
Group A

We studied the mechanism of erythropoietin (EPO)-induced hypertension (HTN) in rats with chronic renal failure (CRF). After partial nephrectomy, rats were randomized into four groups. Group A received EPO, 150 U/kg, two times weekly for 6 wk to prevent anemia; group B received placebo injections and became anemic; group C received EPO but was kept anemic by dietary iron deficiency; and group D received placebo and regular transfusions to match hematocrit (Hct) in group A. Blood pressure (BP), Hct, platelet cytosolic calcium ([Ca2+]i) and magnesium concentration, and pressor and vasodilatory responses were determined. By design, Hct in groups A and D were comparable and significantly greater (P < 0.01) than in groups B and C. Despite divergent Hct values, the EPO-treated groups A and C showed a significant rise in BP compared with the placebo-treated groups B and D. HTN occurred whether EPO therapy was begun immediately or 4 wk after nephrectomy. EPO therapy augmented the elevation of basal [Ca2+]i and restored the defective thrombin-mediated rise of platelet [Ca2+]i in CRF animals. EPO therapy did not alter caudal artery contraction in response to either 68 mM K(+)-induced depolarization, angiotensin II or alpha 1-agonist, methoxamine in vitro, or the pressor response to angiotensin II in vivo. However, EPO therapy impaired the hypotensive response to nitric oxide (NO) donors, sodium nitroprusside and S-nitroso-N-acetyl-D,L-penicillamine, and reversed the CRF-induced upregulation of guanosine 3',5'-cyclic monophosphate production by thoracic aorta in vitro. Thus EPO-induced HTN in CRF rats is Hct independent and is associated with and perhaps causally related to increased basal and stimulated [Ca2+]i and impaired vasodilatory response to NO.

Comparative study of platelet angiotensin II binding and the angiotensin II sensitivity test as predictors of pregnancy-induced hypertension

1992 ◽  
Vol 83 (1) ◽  
pp. 89-95 ◽  
Author(s):  
Philip N. Baker ◽  
Fiona Broughton Pipkin ◽  
E. Malcolm Symonds
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Discriminant Analysis ◽  
Vascular Smooth Muscle ◽  
Comparative Study ◽  
Pressor Response ◽  
Sensitivity Test ◽  
Pregnancy Induced Hypertension ◽  
Induced Hypertension

1. Platelet angiotensin II binding was measured in 34 primigravid women (between 28 and 32 weeks gestation), in whom the pressor response to infused angiotensin II was also determined. 2. There was a significant correlation between the platelet angiotensin II binding and the slope of the curve relating the diastolic pressor response to infused angiotensin II (P<0.01), suggesting that co-linearity between the two techniques exists and supporting the use of platelet angiotensin II binding as a model of vascular smooth muscle pressor responsiveness. 3. Ten of the 34 women subsequently developed pregnancy-induced hypertension. Platelet angiotensin II binding in the patients who subsequently developed pregnancy-induced hypertension was sixfold higher than in the patients who remained normotensive (P < 0.001). There were, however, no significant differences between the groups in any of the parameters derived from the angiotensin II infusion experiments. 4. The use of platelet angiotensin II binding alone in predicting the outcome of the pregnancies, as assessed using discriminant analysis, was more successful than when any of the infusion parameters were used, with 77% of patients being correctly classified.

scholarly journals Endothelium-specific sepiapterin reductase deficiency in DOCA-salt hypertension

2012 ◽  
Vol 302 (11) ◽  
pp. H2243-H2249 ◽  
Author(s):  
Ji Youn Youn ◽  
Ting Wang ◽  
John Blair ◽  
Karine M. Laude ◽  
Jeong-Ho Oak ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Oxidase Inhibitor ◽  
Aortic Endothelial Cells ◽  
Sepiapterin Reductase ◽  
Enos Uncoupling ◽  
Induced Hypertension ◽  
Salt Hypertension ◽  
Endothelial Nitric Oxide ◽  
Aortic Endothelial

The endothelial nitric oxide synthase (eNOS) requires tetrahydrobiopterin (H4B) as a cofactor and, in its absence, produces superoxide (O2·−) rather than nitric oxide (NO·), a condition referred to as eNOS uncoupling. DOCA-salt-induced hypertension is associated with H4B oxidation and uncoupling of eNOS. The present study investigated whether administration of sepiapterin or H4B recouples eNOS in DOCA-salt hypertension. Bioavailable NO· detected by electron spin resonance was markedly reduced in aortas of DOCA-salt hypertensive mice. Preincubation with sepiapterin (10 μmol/l for 30 min) failed to improve NO· bioavailability in hypertensive aortas while it augmented NO· production from control vessels, implicating a hypertension-associated deficiency in sepiapterin reductase (SPR), the rate-limiting enzyme for sepiapterin conversion to H4B. Indeed, a decreased SPR expression was observed in aortic endothelial cells, but not in endothelium-denuded aortic remains, implicating an endothelium-specific SPR deficiency. Administration of hypertensive aortas with H4B (10 μmol/l, 30 min) partially restored vascular NO· production. Combined administration of H4B and the NADPH oxidase inhibitor apocynin (100 μmol/l, 30 min) fully restored NO· bioavailability while reducing O2·− production. In angiotensin II-induced hypertension, however, aortic endothelial SPR expression was not affected. In summary, administration of sepiapterin is not effective in recoupling eNOS in DOCA-salt hypertension, due to an endothelium-specific loss in SPR, whereas coadministration of H4B and apocynin is highly efficient in recoupling eNOS. This is consistent with our previous observations that in angiotensin II hypertension, endothelial deficiency in dihydrofolate reductase is alternatively responsible for uncoupling of eNOS. Taken together, these data indicate that strategies specifically targeting at different H4B metabolic enzymes might be necessary in restoring eNOS function in different types of hypertension.

Abstract P041: Proximal Tubule-specific Deletion Of Angiotensin Ii Type 1a Receptors In The Kidney Lowers Basal Blood Pressure And Attenuates Angiotensin Ii-induced Hypertension By Increasing Glomerular Filtration And The Pressure-natriuresis Response

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Xiao C Li ◽  
Ana P Leite ◽  
Liang Zhang ◽  
Jia L Zhuo
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Pressor Response ◽  
Control Group ◽  
Ang Ii ◽  
Induced Hypertension ◽  
Basal Blood Pressure ◽  
Pressure Natriuresis ◽  
Specific Deletion

The present study tested the hypothesis that intratubular angiotensin II (Ang II) and AT 1a receptors in the proximal tubules of the kidney plays an important role in basal blood pressure control and in the development of Ang II-induced hypertension. Mutant mice with proximal tubule-specific deletion of AT 1a receptors in the kidney, PT- Agtr1a -/- , were generated to test the hypothesis. Eight groups (n=7-12 per group) of adult male wild-type (WT) and PT- Agtr1a -/- mice were infused with or without Ang II for 2 weeks (1.5 mg/kg, i.p.). Basal systolic, diastolic, and mean arterial pressures were ~13 ± 3 mmHg lower in PT- Agtr1a -/- than WT mice ( P <0.01). Basal glomerular filtration rate (GFR), as measured using transdermal FITC-sinistrin, was significantly higher in PT- Agtr1a -/- mice (WT: 160.4 ± 7.0 μl/min vs. PT- Agtr1a -/- : 186.0 ± 6.0 μl/min, P <0.05). Basal 24 h urinary Na + excretion (U Na V) was significantly higher in PT- Agtr1a -/- than WT mice ( P <0.01). In response to Ang II infusion, both WT and PT- Agtr1a -/- mice developed hypertension, and the magnitude of the pressor response to Ang II was similar in WT (Δ43 ± 3 mmHg, P <0.01) and PT- Agtr1a -/- mice (Δ39 ± 5 mmHg, P <0.01). However, the absolute blood pressure level was still 16 ± 3 mmHg lower in PT- Agtr1a -/- mice ( P <0.01). Ang II significantly decreased GFR to 132.2 ± 7.0 μl/min in WT mice ( P <0.01), and to 129.4 ± 18.6 μl/min in PT- Agtr1a -/- mice ( P <0.01), respectively. In WT mice, U Na V increased from 139.3 ± 22.3 μmol/24 h in the control group to 196.4 ± 29.6 μmol/24 h in the Ang II-infused group ( P <0.01). In PT- Agtr1a -/- mice, U Na V increased from 172.0 ± 10.2 μmol/24 h in the control group to 264.7 ± 35.4 μmol/24 h in the Ang II-infused group ( P <0.01). The pressor response to Ang II was attenuated, while the natriuretic response was augmented by losartan in WT and PT- Agtr1a -/- mice ( P <0.01). Finally, proximal tubule-specific deletion of AT 1a receptors significantly augmented the pressure-natriuresis response and natriuretic responses to acute saline infusion ( P <0.01) or a 2% high salt diet ( P <0.01). We concluded that deletion of AT 1a receptors selectively in the proximal tubules lowers basal blood pressure and attenuates Ang II-induced hypertension by increasing GFR and promoting the natriuretic response in PT- Agtr1a -/- mice.

ROLE OF THE NITRIC OXIDE IN THE GENESIS OF PREGNANCY-INDUCED HYPERTENSION

2000 ◽  
Vol 18 ◽  
pp. S203-S204
Author(s):  
B. Gerasimovska ◽  
K. Zafirovska ◽  
S. Bogdanovska ◽  
V. Maleska ◽  
B. Dejanova ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pregnancy Induced Hypertension ◽  
Induced Hypertension

scholarly journals Angiotensin II acts through the angiotensin 1a receptor to upregulate pendrin

2011 ◽  
Vol 301 (6) ◽  
pp. F1314-F1325 ◽  
Author(s):  
Jill W. Verlander ◽  
Seongun Hong ◽  
Vladimir Pech ◽  
James L. Bailey ◽  
Diana Agazatian ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Plasma Membrane ◽  
Angiotensin Ii ◽  
Pressor Response ◽  
Angiotensin Receptors ◽  
Apical Plasma Membrane ◽  
Protein Abundance ◽  
Wild Type ◽  
Induced Hypertension

Pendrin is an anion exchanger expressed in the apical regions of B and non-A, non-B intercalated cells. Since angiotensin II increases pendrin-mediated Cl− absorption in vitro, we asked whether angiotensin II increases pendrin expression in vivo and whether angiotensin-induced hypertension is pendrin dependent. While blood pressure was similar in pendrin null and wild-type mice under basal conditions, following 2 wk of angiotensin II administration blood pressure was 31 mmHg lower in pendrin null than in wild-type mice. Thus pendrin null mice have a blunted pressor response to angiotensin II. Further experiments explored the effect of angiotensin on pendrin expression. Angiotensin II administration shifted pendrin label from the subapical space to the apical plasma membrane, independent of aldosterone. To explore the role of the angiotensin receptors in this response, pendrin abundance and subcellular distribution were examined in wild-type, angiotensin type 1a (Agtr1a) and type 2 receptor (Agtr2) null mice given 7 days of a NaCl-restricted diet (< 0.02% NaCl). Some mice received an Agtr1 inhibitor (candesartan) or vehicle. Both Agtr1a gene ablation and Agtr1 inhibitors shifted pendrin label from the apical plasma membrane to the subapical space, independent of the Agtr2 or nitric oxide (NO). However, Agtr1 ablation reduced pendrin protein abundance through the Agtr2 and NO. Thus angiotensin II-induced hypertension is pendrin dependent. Angiotensin II acts through the Agtr1a to shift pendrin from the subapical space to the apical plasma membrane. This Agtr1 action may be blunted by the Agtr2, which acts through NO to reduce pendrin protein abundance.

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