Reversal of hypertension and endothelial dysfunction in deoxycorticosterone-NaCl-treated rats by high-Ca2+ diet

1996 ◽  
Vol 270 (4) ◽  
pp. H1250-H1257
Author(s):  
H. Makynen ◽  
M. Kahonen ◽  
X. Wu ◽  
H. Wuorela ◽  
I. Porsti
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Methyl Ester ◽  
Endothelial Dysfunction ◽  
Wistar Rats ◽  
Normal Diet ◽  
Synthesis Inhibitor ◽  
K Channels ◽  
Arterial Relaxation

We tested the effect of high-Ca2+ diet on blood pressure and responses of mesenteric arterial rings in vitro in established deoxycorticosterone (DOC)-NaCl hypertension. Ca2+ supplementation (2.5%) of Wistar rats, which was commenced 8 wk after initiation of DOC-NaCl treatment (Ca(2+)-DOC group), reversed the development of hypertension, whereas in animals ingesting a normal diet (1.1% Ca2+; DOC group) blood pressure continued to rise until the end of the 12-wk study. In norepinephrine-precontracted arterial rings, relaxations to acetylcholine (ACh) and sodium nitroprusside were attenuated in the DOC group, but these responses were significantly improved by Ca2+ supplementation. The nitric oxide (NO) synthesis inhibitor NG-nitro-L-arginine methyl ester, in the presence of diclofenac, totally abolished ACh-induced relaxations in the DOC group but only attenuated them in the Ca(2+)-DOC group. The remaining relaxation was further inhibited by apamin, an inhibitor of Ca(2+)-activated K+ channels, and practically abolished after blockade of ATP-dependent K+ channels by glyburide. Interestingly, when endothelium-dependent hyperpolarization was prevented using precontractions induced by KCl, no differences were found in relaxations to ACh between the groups. In conclusion, high-Ca(2+) diet effectively reduced blood pressure in DOC-NaCl hypertension and concomitantly enhanced arterial relaxation. Because the relaxations to ACh in the Ca(2+)-DOC group were augmented in the absence and presence of NO synthesis inhibition but not under conditions of prevented hyperpolarization, these enhanced relaxations could be attributed to promoted endothelium-dependent hyperpolarization in the Ca(2+)-supplemented animals.

Effects of NG-nitro-L-arginine methyl ester on renal function and blood pressure

1991 ◽  
Vol 261 (6) ◽  
pp. F1033-F1037 ◽  
Author(s):  
V. Lahera ◽  
M. G. Salom ◽  
F. Miranda-Guardiola ◽  
S. Moncada ◽  
J. C. Romero
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Renal Function ◽  
Methyl Ester ◽  
Renal Plasma Flow ◽  
Urinary Sodium Excretion ◽  
Systemic Blood Pressure ◽  
Synthesis Inhibitor ◽  
Renal Changes ◽  
Dose Dependent

The dose-dependent effects of intravenous infusions of nitric oxide (NO) synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 0.1, 1, 10, and 50 micrograms.kg-1.min-1), were studied in anesthetized rats to determine whether the inhibitory actions of L-NAME are manifested primarily in alterations of renal function or whether they are the consequences of the increase in systemic blood pressure. Mean arterial pressure (MAP) was not altered by the intravenous L-NAME infusions of 0.1 and 1.0 microgram.kg-1.min-1. However, 0.1 microgram.kg-1.min-1 L-NAME induced a 30% decrease in urine flow rate (UV). The administration of 1.0 microgram.kg-1.min-1 L-NAME, in addition to decreasing UV, also decreased urinary sodium excretion (UNaV) and renal plasma flow (RPF). The intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 produced significant increases in MAP that reversed the initial fall in UV and UNaV, despite decreasing RPF and glomerular filtration rate (GFR). The administration of L-arginine alone (10 micrograms.kg-1.min-1) did not modify any of the parameters measured, but it effectively prevented all the hemodynamic and renal changes induced by the infusion of 50 micrograms.kg-1.min-1 L-NAME. These results suggest that the decrease in nitric oxide production induced by the intravenous infusion of L-NAME affects renal excretion of sodium and water in the absence of any significant change in blood pressure. At larger doses, L-NAME also produces hypertension that overrides the initial antinatriuretic effect.

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.

Angiotensin II and alpha 1-adrenergic tone in chronic nitric oxide blockade-induced hypertension

1994 ◽  
Vol 266 (5) ◽  
pp. R1470-R1476 ◽  
Author(s):  
C. Qiu ◽  
K. Engels ◽  
C. Baylis
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Methyl Ester ◽  
Normal Animal ◽  
Synthesis Inhibitor ◽  
Conscious Rats ◽  
Induced Hypertension ◽  
Renal Vascular

Nitric oxide (NO) is a tonically produced vasodilator that maintains blood pressure (BP) in the normal animal. In these studies, we produced chronic NO blockade by oral administration of the NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME), which produced sustained hypertension and increased renal vascular resistance (RVR) in conscious rats. Acute blockade of the angiotensin II type 1 (AT1) receptor with losartan had little effect on BP and RVR in either chronically NO-blocked or normal conscious rats. Acute blockade of the alpha 1-adrenoceptor with prazosin produced moderate similar falls in BP in both chronically NO-blocked and normal rats. The combination of AT1 and alpha 1-adrenoceptor blockade was profoundly antihypertensive and was particularly effective in lowering BP in chronically NO-blocked rats where the hypertension was obliterated. In contrast, the increased RVR persisted in chronically NO-blocked rats receiving combined acute AT1 and alpha 1-adrenoceptor blockade. These observations indicate that, in the sustained phase of chronic NO blockade, the hypertension is largely due to the combined activities of alpha 1-adrenoceptor and AT1 stimulation.

Hepatic glutathione and nitric oxide are critical for hepatic insulin-sensitizing substance action

2003 ◽  
Vol 284 (4) ◽  
pp. G588-G594 ◽  
Author(s):  
Maria P. Guarino ◽  
Ricardo A. Afonso ◽  
Nuno Raimundo ◽  
João F. Raposo ◽  
M. Paula Macedo
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Methyl Ester ◽  
Insulin Action ◽  
Wistar Rats ◽  
Treated Group ◽  
Synthesis Inhibitor ◽  
No Donor ◽  
Hepatic Glutathione

We tested the hypothesis that hepatic nitric oxide (NO) and glutathione (GSH) are involved in the synthesis of a putative hormone referred to as hepatic insulin-sensitizing substance HISS. Insulin action was assessed in Wistar rats using the rapid insulin sensitivity test (RIST). Blockade of hepatic NO synthesis with N G-nitro-l-arginine methyl ester (l-NAME, 1.0 mg/kg intraportal) decreased insulin sensitivity by 45.1 ± 2.1% compared with control (from 287.3 ± 18.1 to 155.3 ± 10.1 mg glucose/kg, P < 0.05). Insulin sensitivity was restored to 321.7 ± 44.7 mg glucose/kg after administration of an NO donor, intraportal SIN-1 (5 mg/kg), which promotes GSH nitrosation, but not after intraportal sodium nitroprusside (20 nmol · kg−1 · min−1), which does not nitrosate GSH. We depleted hepatic GSH using the GSH synthesis inhibitor l-buthionine-[ S,R]-sulfoximine (BSO, 2 mmol/kg body wt ip for 20 days), which reduced insulin sensitivity by 39.1%. Insulin sensitivity after l-NAME was not significantly different between BSO- and sham-treated animals. SIN-1 did not reverse the insulin resistance induced by l-NAME in the BSO-treated group. These results support our hypothesis that NO and GSH are essential for insulin action.

Contribution of Vascular Nitric Oxide to Basal Blood Pressure in Conscious Spontaneously Hypertensive Rats and Normotensive Wistar Kyoto Rats

1995 ◽  
Vol 89 (2) ◽  
pp. 177-182 ◽  
Author(s):  
Naoyoshi Minami ◽  
Yutaka Imai ◽  
Jun-Ichiro Hashimoto ◽  
Keishi Abe
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Methyl Ester ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Basal Blood Pressure ◽  
Wistar Kyoto

1. The aim of this study was to clarify the extent to which vascular nitric oxide contributes to basal blood pressure in conscious spontaneously hypertensive rats and normotensive Wistar Kyoto rats. 2. The contribution of vascular nitric oxide to maintenance of blood pressure was estimated by measuring the pressor response to an intravenous injection of nitric oxide synthase inhibitor, Nω-l-arginine methyl ester, given after serial injections of captopril, vasopressin V1-receptor antagonist (V1-antagonist) and ganglion blocker (pentolinium) in conscious spontaneously hypertensive and Wistar Kyoto rats aged 20–28 weeks. To estimate the ‘amplifier property’ of hypertrophied vasculature in spontaneously hypertensive rats, which is known to modulate pressor responses, the lower blood pressure plateau after serial injections of captopril, V1-antagonist and pentolinium and the maximum blood pressure elicited by subsequent injection of increasing doses of phenylephrine were also measured. 3. The serial injections of captopril, V1-antagonist and pentolinium decreased mean arterial pressure from 164 ± 9 mmHg to 67 ± 2 mmHg and from 117 ± 2 mmHg to 49 ± 1 mmHg in spontaneously hypertensive and Wistar Kyoto rats respectively. The subsequent injection of Nω-l-arginine methyl ester restored mean arterial pressure almost to its control levels in both spontaneously hypertensive and Wistar Kyoto rats. The absolute changes in mean arterial pressure elicited by Nω-l-arginine methyl ester were significantly greater in spontaneously hypertensive than in Wistar Kyoto rats (P < 0.01), but there was no significant difference in the responses to Nω-l-arginine methyl ester when they were expressed as percentages of either the lower blood pressure plateau or maximum blood pressure. 4. These results indicate that basal blood pressure in both spontaneous hypertensive and Wistar Kyoto rats is maintained by a balance between vascular nitric oxide and major pressor systems. They also suggest that the vasodilatory effect of vascular nitric oxide does not differ between spontaneously hypertensive and Wistar Kyoto rats, and that the increased pressor effect of Nω-l-arginine methyl ester in spontaneously hypertensive rats is due to a vascular amplifier mechanism.

Abstract 17853: Activation of AMP-activated Protein Kinase (AMPKα) by AICAR Attenuates Klotho Deficiency-induced Endothelial Dysfunction, Arterial Stiffening and Hypertension

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yi Lin ◽  
Zhongjie Sun
Keyword(s):  
Blood Pressure ◽  
Blood Glucose ◽  
Endothelial Dysfunction ◽  
Protein Expression ◽  
Normal Diet ◽  
Collagen I ◽  
Daily Injection ◽  
Arterial Stiffening ◽  
Glucose Levels ◽  
Amp Activated Protein Kinase

Background: Arterial stiffening and hypertension are progressive aging-related disorders. Klotho (KL) is a recently-discovered anti-aging gene but its role in the pathogenesis of endothelial dysfunction, arterial stiffening and hypertension is not fully understood. Methods and Results: Heterozygous Klotho deficiency ( KL +/- ) mice and WT littermate mice were fed on high fat diet (HFD) or normal diet (ND). Plasma KL in KL heterozygeous mice (+/-) is about a half of that of the WT mice. Pulse wave velocity (PWV), an index of arterial stiffening, was increased in KL +/- mice but not in WT mice fed on HFD for 4 weeks. Systolic blood pressure and blood glucose levels were increased earlier with greater magnitudes in KL +/- mice than in WT mice fed on HFD. Notably, protein expression of collagen I, Runx2, and TGFβ1 were increased but protein expression of phosphorylated AMPKα (pAMPKα), phosphorylated eNOS (peNOS), and Mn-SOD were decreased in aortas of KL +/- mice fed on HFD for 5 weeks. Interestingly, daily injection of AICAR, an activator of AMPK, abolished the increases in PWV, blood pressure, and blood glucose in KL +/- mice fed on HFD. AICAR not only abolished the downregulation of pAMPKα, peNOS, and Mn-SOD levels but also attenuated the increased levels of collagen I, Runx2, TGFβ1 and superoxide, elastic lamellae breaks, and calcification in aortas in KL +/- mice fed on HFD. Conclusions: Klohto deficiency promotes HFD-induced endothelial dysfunction, arterial stiffening and hypertension. The promoting effects of klotho deficiency on arterial stiffening may be due to downregulation of endothelial AMPKα activity.

Endothelium-dependent vasodilation of cerebral arteries is altered with simulated microgravity through nitric oxide synthase and EDHF mechanisms

2006 ◽  
Vol 101 (1) ◽  
pp. 348-353 ◽  
Author(s):  
Rhonda D. Prisby ◽  
M. Keith Wilkerson ◽  
Elke M. Sokoya ◽  
Robert M. Bryan ◽  
Emily Wilson ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Nitric Oxide Synthase ◽  
Cerebral Perfusion ◽  
Simulated Microgravity ◽  
Cerebral Arteries ◽  
Caveolin 1 ◽  
Fluid Shifts ◽  
Oxide Synthase

Cephalic elevations in arterial pressure associated with microgravity and prolonged bed rest alter cerebrovascular autoregulation in humans. Using the head-down tail-suspended (HDT) rat to chronically induce headward fluid shifts and elevate cerebral artery pressure, previous work has likewise shown cerebral perfusion to be diminished. The purpose of this study was to test the hypothesis that 2 wk of HDT reduces cerebral artery vasodilation. To test this hypothesis, dose-response relations for endothelium-dependent (2-methylthioadenosine triphosphate and bradykinin) and endothelium-independent (nitroprusside) vasodilation were determined in vitro in middle cerebral arteries (MCAs) from HDT and control rats. All in vitro measurements were done in the presence and absence of the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (10−5 M) and cyclooxygenase inhibitor indomethacin (10−5 M). MCA caveolin-1 protein content was measured by immunoblot analysis. Endothelium-dependent vasodilation to 2-methylthioadenosine triphosphate and bradykinin were both lower in MCAs from HDT rats. These lower vasodilator responses were abolished with NG-nitro-l-arginine methyl ester but were unaffected by indomethacin. In addition, HDT was associated with lower levels of MCA caveolin-1 protein. Endothelium-independent vasodilation was not altered by HDT. These results indicate that chronic cephalic fluid shifts diminish endothelium-dependent vasodilation through alterations in the endothelial nitric oxide synthase signaling mechanism. Such decrements in endothelium-dependent vasodilation of cerebral arteries could contribute to the elevations in cerebral vascular resistance and reductions in cerebral perfusion that occur after conditions of simulated microgravity in HDT rats.

Abstract 15696: Cytochrome B5 Reductase 3 Sensitizes Soluble Guanylate Cyclase to Nitric Oxide

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Anh T Nguyen ◽  
Mizanur M Rahaman ◽  
Stephanie M Mutchler ◽  
Megan Miller ◽  
Josef T Prchal ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Soluble Guanylate Cyclase ◽  
Cytochrome B5 ◽  
Heme Iron ◽  
Proximity Ligation Assay ◽  
Cytochrome B5 Reductase ◽  
Cgmp Production ◽  
Iron Reductase

Impaired soluble guanylyl cyclase (sGC)-dependent nitric oxide (NO) signaling has been linked to numerous cardiovascular diseases (CVD) such as hypertension, myocardial infarction and atherosclerosis. Despite emerging evidence indicating the importance of sGC function within the cardiovascular system, the basic mechanisms that regulate sGC activity remain incompletely understood. Herein, we provide in vitro and in vivo evidence that cytochrome b5 reductase 3 (Cyb5R3) is an sGC heme iron reductase and regulates downstream cGMP signaling. Of major significance, we also demonstrate that a Cyb5R3 T116S polymorphism with allele frequency of 0.23 in African Americans associates with increase blood pressure and is incapable of reducing sGC. Proximity ligation assay (PLA) experiments show that endogenous Cyb5R3 and oxidized sGC associate. Knockdown of Cyb5R3 results in reduced cGMP production and downstream signaling in rat aortic smooth muscle cells (SMC). Overexpression of Cyb5R3 not only rescues cGMP production but also increases baseline cGMP, whereas T116S mutant does not. Finally, inhibition of Cyb5R3 in mice significantly increases systemic blood pressure. Our studies are the first to identify an sGC heme iron reductase, provide evidence for Cyb5R3 as a key biological regulator of sGC activity and vascular tone in SMC, and link a human polymorphism of Cyb5R3 to increased blood pressure; all of which may lead to the development of novel therapeutics targeting Cyb5R3 for the treatment of CVD. Importantly, the co-expression of Cyb5R3 and sGC in multiple cells types suggests that this regulation of sGC activity may have broad applications for multiple physiological and pathophysiological processes. Results: Conclusions:

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