scholarly journals Nicorandil as a novel therapy for advanced diabetic nephropathy in the eNOS-deficient mouse

2012 ◽  
Vol 302 (9) ◽  
pp. F1151-F1160 ◽  
Author(s):  
Katsuyuki Tanabe ◽  
Miguel A. Lanaspa ◽  
Wataru Kitagawa ◽  
Christopher J. Rivard ◽  
Makoto Miyazaki ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Diabetic Nephropathy ◽  
Oxidant Stress ◽  
Nitric Oxide Donor ◽  
K Channel ◽  
Glomerular Injury ◽  
Novel Therapy ◽  
Glucose Levels ◽  
Stress Studies

Nicorandil is an orally available drug that can act as a nitric oxide donor, an antioxidant, and an ATP-dependent K channel activator. We hypothesized that it may have a beneficial role in treating diabetic nephropathy. We administered nicorandil to a model of advanced diabetic nephropathy (the streptozotocin-induced diabetes in mice lacking endothelial nitric oxide synthase, eNOSKO); controls included diabetic eNOS KO mice without nicorandil and nondiabetic eNOS KO mice treated with either nicorandil or vehicle. Mice were treated for 8 wk. Histology, blood pressure, and renal function were determined. Additional studies involved examining the effects of nicorandil on cultured human podocytes. Here, we found that nicorandil did not affect blood glucose levels, blood pressure, or systemic endothelial function, but significantly reduced proteinuria and glomerular injury (mesangiolysis and glomerulosclerosis). Nicorandil protected against podocyte loss and podocyte oxidative stress. Studies in cultured podocytes showed that nicorandil likely protects against glucose-mediated oxidant stress via the ATP-dependent K channel as opposed to its NO-stimulating effects. In conclusion, nicorandil may be beneficial in diabetic nephropathy by preserving podocyte function. We recommend clinical trials to determine whether nicorandil may benefit diabetic nephropathy or other conditions associated with podocyte dysfunction.

Contribution of the nitric oxide donor molsidomine and the antiparkinsonian drug l-DOPA to the modulation of the blood pressure in unilaterally 6-OHDA-lesioned rats

2017 ◽  
Vol 69 (1) ◽  
pp. 29-35 ◽  
Author(s):  
Elżbieta Lorenc-Koci ◽  
Anna Czarnecka ◽  
Kinga Kamińska ◽  
Joanna Knutelska ◽  
Małgorzata Zygmunt ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Donor ◽  
Antiparkinsonian Drug

scholarly journals Addition of a Nitric Oxide Donor to an Angiotensin II Type 1 Receptor Blocker May Cancel Its Blood Pressure-Lowering Effects

2015 ◽  
Vol 56 (6) ◽  
pp. 656-660 ◽  
Author(s):  
Eiji Yahiro ◽  
Shin-ichiro Miura ◽  
Yasunori Suematsu ◽  
Yoshino Matsuo ◽  
Tadaaki Arimura ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Receptor Blocker ◽  
Nitric Oxide Donor ◽  
Blood Pressure Lowering ◽  
Pressure Lowering

Abstract P215: Hyperglycemic Rats Have Increased Fetal Demise But Not Hypertension During Pregnancy

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Frank T Spradley ◽  
Barbara Wilson ◽  
Christopher Anderson
Keyword(s):  
Blood Pressure ◽  
Epidemiological Studies ◽  
Adverse Outcomes ◽  
Nitric Oxide Donor ◽  
Gk Rat ◽  
Pregnant Rats ◽  
Fetal Demise ◽  
Glucose Levels ◽  
Maternal Hypertension ◽  
Placental Ischemia

While obesity is a major cause for pregnancy complications including preeclampsia and fetal demise, it is not exactly clear the precise obesity-related metabolic factors that promote these adverse outcomes. Epidemiological studies have pointed toward hyperglycemia as one such factor. Therefore, we tested the hypothesis that hyperglycemic rats have hypertension and fetal demise during pregnancy. For this purpose, we utilized the type II diabetic model, the Goto-Kakizaki (GK) rat (N=16), compared to normoglycemic Wistar Hannover (WH) rats (N=9), which were maintained on Envigo 8640 standard chow. The GK rat allows for assessment of hyperglycemia on pregnancy without confounding obesity. Maternal fasting glucose levels were significantly greater (P<0.05) in GK (97±8 mg/dL) vs. WH (72±9 mg/dL) rats by gestational day 19. Body weight was lower (P<0.05) in GK (248±4 g) versus WH (289±4 g) pregnant rats, whereas perirenal fat (1.56±0.07 g vs. 1.38±0.07 g, P>0.05) and circulating levels of the adipokine, leptin (1.6±0.2 ng/mL vs. 2.2±0.3 ng/mL, P>0.05) were similar between GK and WH pregnant groups, respectively. Endothelial-dependent relaxation to acetylcholine (sensitivity as logEC50: -5.2±0.3 M vs -5.2±0.4 M) and endothelial-independent relaxation to the nitric oxide-donor sodium nitroprusside (logEC50: -7.2±0.2 M vs. -7.5±0.1 M) were similar (P>0.05) in uterine arteries isolated from GK and WH rats, respectively. It was then determined if reduced uterine perfusion pressure (RUPP)-induced placental ischemia, a significant contributor to the development of preeclampsia, promoted greater maternal hypertension in GK rats. RUPP was conducted on gestational day 14 and blood pressure assessed on day 19. RUPP produced hypertension to a similar extent (P>0.05) in GK (116±5 mmHg vs. Sham 102±5 mmHg) and WH (124±4 mmHg vs. Sham 100±2 mmHg) groups. Blood pressure was similar under Sham conditions. Fetal demise was already greater in Sham GK vs. Sham WH pregnant rats (% absorptions: 13±2 vs. 2±2, P<0.05) but increased similarly following RUPP in GK (61±11 %) and WH (65±5 %) pregnant rats. In conclusion, these data suggest that high glucose levels promote fetal demise during pregnancy but do not exaggerate the outcomes of placental ischemia-induced hypertension.

scholarly journals ACE (Angiotensin-Converting Enzyme) Inhibition Reverses Vasoconstriction and Impaired Dilation of Pial Collaterals in Chronic Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 226-235 ◽  
Author(s):  
Zhaojin Li ◽  
Devon P. Lindner ◽  
Nicole M. Bishop ◽  
Marilyn J. Cipolla
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Drinking Water ◽  
Angiotensin Converting Enzyme ◽  
Wistar Rats ◽  
Nitric Oxide Donor ◽  
Chronic Hypertension ◽  
Stroke Outcome ◽  
Converting Enzyme ◽  
Vasodilatory Response

Leptomeningeal anastomoses (LMAs) are pial collaterals that perfuse the penumbra and important for stroke outcome. We previously showed LMAs from SHRs (spontaneously hypertensive rats) were vasoconstricted compared with normotensive Wistar rats. Here, we investigated mechanisms by which hypertension causes LMA vasoconstriction. SHRs were treated with the ACE (angiotensin-converting enzyme) inhibitor captopril, an Ang II (angiotensin II)–independent antihypertensive agent hydralazine, or vehicle for 5 weeks in drinking water (n=8/group). A group of Wistar rats (n=8) had regular drinking water served as controls. Blood pressure was measured twice weekly by tail-cuff. LMAs were isolated and studied under pressurized conditions. Vasoreactivity of LMAs, including myogenic responses, reactivity to Rho-kinase inhibitor Y-27632, and nitric oxide were measured. Both captopril and hydralazine lowered blood pressure in SHRs similar to Wistar. However, only captopril normalized LMA increased tone compared with untreated SHRs (15±2% versus 50±3%; P <0.01) that was similar to Wistar (16±2%) but not hydralazine (38±6%; P >0.05). Vasodilatory response of LMAs to Y-27632 was impaired in SHRs compared with Wistar (28±3% versus 81±4%; P <0.01) that was restored by captopril (84±5%; P <0.01) and partially hydralazine (59±4%). LMAs from all groups constricted similarly to NOS (NO synthase) inhibition; however, the vasodilatory response of LMAs to the nitric oxide donor sodium nitroprusside was impaired in SHRs compared with Wistar rats (29±4% versus 80±2%; P <0.01) that was restored by captopril (84±4%; P <0.01), not hydralazine (38±8%; P >0.05). These results suggest that ACE inhibition during chronic hypertension reversed vascular dysfunction and hyperconstriction of LMAs that could improve stroke outcome by increasing collateral perfusion.

scholarly journals Effects of Rut-bpy (Cis-[Ru(bpy)2(SO3)(NO)]PF 6), a novel nitric oxide donor, in L-NAME-induced hypertension in rats

2011 ◽  
Vol 26 (suppl 1) ◽  
pp. 57-59 ◽  
Author(s):  
Marcio Wilker Soares Campelo ◽  
Ana Paula Bomfim Soares Campelo ◽  
Luiz Gonzaga de França Lopes ◽  
Armenio Aguiar dos Santos ◽  
Sergio Botelho Guimarães ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Methyl Ester ◽  
Arterial Blood Pressure ◽  
Wistar Rats ◽  
Nitric Oxide Donor ◽  
Hypertensive Rats ◽  
Arterial Blood ◽  
Induced Hypertension ◽  
Male Wistar Rats

PURPOSE: To evaluate the effect of Rut-bpy (Cis-[Ru(bpy)2(SO3)(NO)]PF 6), a novel nitric oxide donor in Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. METHODS: Twenty-four male Wistar rats were randomly assigned to four groups (n=6), named according to the treatment applied (G1-Saline, G2-Rut-bpy, G3-L-NAME and G4-L-NAME+Rut-bpy). L-NAME (30 mg/Kg) was injected intraperitoneally 30 minutes before the administration of Rut-bpy (100 mg/Kg). Mean abdominal aorta arterial blood pressure (MAP) was continuously monitored. RESULTS: Mean arterial blood pressure (MAP) in G3 rats rose progressively, reaching 147±16 mmHg compared with 100±19 mm Hg in G1 rats (p<0.05). In G4 rats, treated with L-NAME+Rut-bpy, MAP reached 149+11 mm Hg while in G2 rats, treated with Rut-bpy, MAP values were 106±11 mm Hg. In G1 rats these values decreased progressively reaching 87+14 mm Hg after 30 minutes. An important finding was the maintenance of the MAP throughout the experiment in G2 rats. CONCLUSION: Rut-bpy does not decrease the MAP in L-Name induced hypertensive rats. However, when it is used in anesthetized hypotensive rats a stable blood pressure is obtained.

Low-dose dexamethasone in the rat: a model to study insulin resistance

2002 ◽  
Vol 283 (2) ◽  
pp. E367-E373 ◽  
Author(s):  
C. Severino ◽  
P. Brizzi ◽  
A. Solinas ◽  
G. Secchi ◽  
M. Maioli ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Blood Pressure ◽  
Insulin Sensitivity ◽  
Isosorbide Dinitrate ◽  
Low Dose ◽  
Tap Water ◽  
Nitric Oxide Donor ◽  
Concomitant Treatment ◽  
Set Up

The main aim of this study was to set up a new animal model to study insulin resistance. Wistar rats (6 or 7 per group) received the following for 4 wk in experiment 1: 1) vehicle, 2) 2 μg/day subcutaneous dexamethasone, 3) metformin (400 mg · kg−1 · day−1 os), and 4) dexamethasone plus metformin. In experiment 2the rats received the following: 1) vehicle, 2) dexamethasone, 3) dexamethasone plus arginine (2%; as substrate of the nitric oxide synthase for nitric oxide production) in tap water, and 4) dexamethasone plus isosorbide dinitrate (70 mg/kg; as direct nitric oxide donor) in tap water. Insulin sensitivity was significantly reduced by dexamethasone already at week 1, before the increase in blood pressure ( day 15) and without significant changes in body weight compared with vehicle. Dexamethasone-treated rats had significantly higher triglycerides, hematocrit, and insulin, whereas serum total nitrates/ nitrites were lower compared with vehicle. The concomitant treatment with metformin minimized all the described effects of dexamethasone. In experiment 2, only isosorbide dinitrate was able to prevent the observed dexamethasone-induced metabolic, hemodynamic, and insulin sensitivity changes. Chronic low-dose subcutaneous dexamethasone (2 μg/day) is a useful model to study the relationships between insulin resistance and blood pressure in the rat, and dexamethasone might decrease insulin sensitivity and increase blood pressure through an endothelium-mediated mechanism.

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