Reduced sensitivity of the renal circulation to angiotensin II in pregnant rats pretreated with captopril: role of nitric oxide

Although obesity increases the risk for hypertension in pregnancy, the mechanisms responsible are unknown. Increased nitric oxide (NO) production results in vasodilation and reduced blood pressure during normal pregnancy in lean rats; however, the role of NO is less clear during obese pregnancies. We examined the impact of obesity on NO synthase (NOS)-mediated regulation of blood pressure during pregnancy by testing the hypothesis that NOS activity, expression, and regulation of vascular tone and blood pressure are reduced in obese pregnant rats. At gestational day 19, melanocortin-4 receptor (MC4R)-deficient obese rats (MC4R) had greater body weight and fat mass with elevated blood pressure and circulating sFlt-1 levels compared with MC4R pregnant rats. MC4R pregnant rats also had less circulating cGMP levels and reduced total NOS enzymatic activity and expression in mesenteric arteries. Despite decreased biochemical measures of NO/NOS in MC4R rats, NOS inhibition enhanced vasoconstriction only in mesenteric arteries from MC4R rats, suggesting greater NOS-mediated tone. To examine the role of NOS on blood pressure regulation in obese pregnant rats, MC4R and MC4R pregnant rats were administered the nonselective NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 100 mg/l) from gestational day 14 to 19 in drinking water. The degree by which l-NAME raised blood pressure was similar between obese and lean pregnant rats. Although MC4R obese pregnant rats had elevated blood pressure associated with reduced total NOS activity and expression, they had enhanced NOS-mediated attenuation of vasoconstriction, with no evidence of alterations in NOS-mediated regulation of blood pressure.

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Losartan Increases No Production from the Bovine Aortic Wall That is Stimulated by Angiotensin II

European Journal of Inflammation ◽

10.1177/1721727x0300100304 ◽

2003 ◽

Vol 1 (3) ◽

pp. 113-117 ◽

Cited By ~ 1

Author(s):

M. Myronidou ◽

B. Kokkas ◽

A. Kouyoumtzis ◽

N. Gregoriadis ◽

A. Lourbopoulos ◽

...

Keyword(s):

Nitric Oxide ◽

Angiotensin Ii ◽

Aortic Wall ◽

Vascular Wall ◽

Protective Role ◽

Normal Function ◽

No Production ◽

Chemical Inactivation

In these studies we investigated if losartan, an AT1- receptor blocker has any beneficial effect on NO production from the bovine aortic preparations in vitro while under stimulation from angiotensin II. Experiments were performed on intact specimens of bovine thoracic aorta, incubated in Dulbeco's MOD medium in a metabolic shaker for 24 hours under 95 % O2 and 5 % CO2 at a temperature of 37°C. We found that angiotensin II 1nM−10 μM does not exert any statistically significant action on NO production. On the contrary, angiotensin II 10nM increases the production of NO by 58.14 % (from 12.16 + 2.9 μm/l to 19.23 + 4.2 μm/l in the presence of losartan 1nM (P<0.05). Nitric oxide levels depend on both rate production and rate catabolism or chemical inactivation. Such an equilibrium is vital for the normal function of many systems including the cardiovascular one. The above results demonstrate that the blockade of AT1-receptors favors the biosynthesis of NO and indicate the protective role of losartan on the vascular wall.

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Apoptotic cascade initiated by angiotensin II in neonatal cardiomyocytes: role of DNA damage

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00408.2003 ◽

2003 ◽

Vol 285 (6) ◽

pp. H2364-H2372 ◽

Cited By ~ 51

Author(s):

Valentina Grishko ◽

Viktor Pastukh ◽

Viktoriya Solodushko ◽

Mark Gillespie ◽

Junichi Azuma ◽

...

Keyword(s):

Nitric Oxide ◽

Dna Damage ◽

Angiotensin Ii ◽

Nadph Oxidase ◽

Ventricular Remodeling ◽

Oxidase Inhibitor ◽

Neonatal Cardiomyocytes ◽

Diphenylene Iodonium ◽

Nitric Oxide Inhibitor

Angiotensin II contributes to ventricular remodeling by promoting both cardiac hypertrophy and apoptosis; however, the mechanism underlying the latter phenomenon is poorly understood. One possibility that has been advanced is that angiotensin II activates NADPH oxidase, generating free radicals that trigger apoptosis. In apparent support of this notion, it was found that angiotensin II-mediated apoptosis in the cardiomyocyte is blocked by the NADPH oxidase inhibitor diphenylene iodonium. However, three lines of evidence suggest that peroxynitrite, rather than superoxide, is responsible for angiotensin II-mediated DNA damage and apoptosis. First, the inducible nitric oxide inhibitor aminoguanidine prevents angiotensin II-induced DNA damage and apoptosis. Second, based on ligation-mediated PCR, the pattern of angiotensin II-induced DNA damage resembles peroxynitritemediated damage rather than damage caused by either superoxide or nitric oxide. Third, angiotensin II activates p53 through the phosphorylation of Ser15 and Ser20, residues that are commonly phosphorylated in response to DNA damage. It is proposed that angiotensin II promotes the oxidation of DNA, which in turn activates p53 to mediate apoptosis.

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Role of AT1 receptors in the renal papillary effects of acute and chronic nitric oxide inhibition

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.274.3.r760 ◽

1998 ◽

Vol 274 (3) ◽

pp. R760-R766 ◽

Cited By ~ 8

Author(s):

M. Clara Ortíz ◽

Lourdes A. Fortepiani ◽

Francisco M. Ruiz-Marcos ◽

Noemí M. Atucha ◽

Joaquín García-Estañ

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Angiotensin Ii ◽

Chronic Administration ◽

Acute Administration ◽

Synthesis Inhibitor ◽

Renal Vasoconstriction ◽

Oxide Inhibition ◽

Stimulation Of

Nitric oxide (NO) is a vasodilator substance controlling renal papillary blood flow (PBF) in the rat. In this study we have evaluated the role of AT1 angiotensin II receptors as modulators of the whole kidney and papillary vasoconstrictor effects induced by the acute or chronic inhibition of NO synthesis. Experiments have been performed in anesthetized, euvolemic Munich-Wistar rats prepared for the study of renal blood flow (RBF) and PBF. In normal rats, acute administration of the NO synthesis inhibitor N ω-nitro-l-arginine methyl ester (l-NAME) increased mean arterial pressure (MAP) and decreased RBF and PBF. Either acute or chronic treatment with the AT1 receptor blocker losartan did not modify the decreases in RBF or PBF secondary to l-NAME. In animals made hypertensive by chronic inhibition of NO, basal MAP was higher, whereas RBF and PBF were lower than in the controls. In these animals, acute or chronic administration of losartan decreased MAP and increased both RBF and PBF significantly. These results indicate that, under normal conditions, the decreases in RBF or PBF induced by the acute inhibition of NO synthesis are not modulated by AT1-receptor stimulation. However, the arterial hypertension, renal vasoconstriction, and reduced PBF present in chronic NO-deficient hypertensive rats is partially due to the effects of angiotensin II, via stimulation of AT1-receptors.

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