Sex differences in the development of angiotensin II-induced hypertension in conscious mice

Xue, Baojian; Pamidimukkala, Jaya; Hay, Meredith

doi:10.1152/ajpheart.00969.2004

Cited by 222 publications

(231 citation statements)

References 71 publications

Supporting

Mentioning

193

Contrasting

Unclassified

Order By: Relevance

“…Our blood pressure results are limited because we only used a noninvasive tail-cuff method, a technique that has received criticism in the past. Although we may have missed subtle blood pressure differences between genotypes with this technique, the overall effect of ANG II treatment on blood pressure was clearly evident and within the range reported by others investigators with similar doses in which either the tail-cuff method or telemetric devices were being used (13,41).…”

Section: Discussionsupporting

confidence: 77%

See 1 more Smart Citation

Role of asymmetric dimethylarginine for angiotensin II-induced target organ damage in mice

Jacobi¹,

Maas²,

Cordasic³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

RH, Hilgers KF. Role of asymmetric dimethylarginine for angiotensin II-induced target organ damage in mice. Am J Physiol Heart Circ Physiol 294: H1058-H1066, 2008. First published December 21, 2007 doi:10.1152/ajpheart.01103.2007.-The aim of the present study was to investigate the role of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) and its degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH) in angiotensin II (ANG II)-induced hypertension and target organ damage in mice. Mice transgenic for the human DDAH1 gene (TG) and wild-type (WT) mice (each, n ϭ 28) were treated with 1.0 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ANG II, 3.0 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ANG II, or phosphate-buffered saline over 4 wk via osmotic minipumps. Blood pressure, as measured by tail cuff, was elevated to the same degree in TG and WT mice. Plasma levels of ADMA were lower in TG than WT mice and were not affected after 4 wk by either dose of ANG II in both TG and WT animals. Oxidative stress within the wall of the aorta, measured by fluorescence microscopy using the dye dihydroethidium, was significantly reduced in TG mice. ANG II-induced glomerulosclerosis was similar between WT and TG mice, whereas renal interstitial fibrosis was significantly reduced in TG compared with WT animals. Renal mRNA expression of protein arginine methyltransferase (PRMT)1 and DDAH2 increased during the infusion of ANG II, whereas PRMT3 and endogenous mouse DDAH1 expression remained unaltered. Chronic infusion of ANG II in mice has no effect on the plasma levels of ADMA after 4 wk. However, an overexpression of DDAH1 alleviates ANG II-induced renal interstitial fibrosis and vascular oxidative stress, suggesting a blood pressure-independent effect of ADMA on ANG II-induced target organ damage. dimethylarginine dimethylaminohydrolase; hypertension; transgenic ASYMMETRIC DIMETHYLARGININE (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is increasingly recognized as a potential risk factor and prognostic biomarker in cardiovascular disease (38). Thus far, elevated ADMA levels have been associated with all established cardiovascular risk factors (38). Furthermore, recent data from genetic mouse models indicate a causal role for ADMA in the pathophysiology of vascular disease (7,19). ADMA derives from the posttranslational methylation of L-arginine residues within proteins catalyzed by enzymes called protein arginine methyltransferases (PRMTs). Upon proteolysis, methylarginines are released into the circulation. Although ϳ15% of ADMA are excreted via the urine, the major elimination occurs through enzymatic degradation (ϳ85%) (1). The enzyme dimethylarginine dimethylaminohydrolase (DDAH), of which two isoforms with distinct tissue distribution have been described, catalyzes the hydrolysis of ADMA to L-citrulline and dimethylamine (38).Thus far, clinical studies have mostly addressed the prognostic value of ADMA in cardiovascular or kidney disease as well as the impact of pharmacological interventions aimed at lowering ADMA levels ...

show abstract

Section: Discussionsupporting

confidence: 77%

“…The dose of 1.0 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ANG II is most commonly used in rodents and causes relevant elevations of blood pressure as measured by tail-cuff plethysmography or telemetric devices (13,41).…”

Section: Ang II Infusionmentioning

confidence: 99%

Role of asymmetric dimethylarginine for angiotensin II-induced target organ damage in mice

Jacobi¹,

Maas²,

Cordasic³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…It has been reported that chronic low-dose ANG II-induced hypertension, which develops over a period of days, is not due to the peripheral vasoconstrictor activity of ANG II, but is most likely the result of excitation of the sympathetic nerve activity (8,17). Recent studies from our laboratory have shown in mice that decreases in blood pressure induced by ganglionic blockade are much smaller on day 1 as compared to day 7 of ANG II infusion, thus suggesting that an enhancement of sympathetic outflow contributes to the ANG II-induced progressive increase in blood pressure (21). The results obtained by Hendel and Collister (18) confirm that the chronic phase of ANG II hypertension has a significant neurogenic component and that this sympathoexcitation is mediated via the subfornical organ.…”

Section: Sex Differences In Angiotensin Iiinduced Hypertensionmentioning

confidence: 90%

Sex differences in angiotensin II- induced hypertension

Xue¹,

Johnson²,

Hay³

2007

Braz J Med Biol Res

View full text Add to dashboard Cite

Sex differences in the development of hypertension and cardiovascular disease have been described in humans and in animal models. In this paper we will review some of our studies which have as their emphasis the examination of the role of sex differences and sex steroids in modulating the central actions of angiotensin II (ANG II) via interactions with free radicals and nitric oxide, generating pathways within brain circumventricular organs and in central sympathomodulatory systems. Our studies indicate that low-dose infusions of ANG II result in hypertension in wild-type male mice but not in intact wild-type females. Furthermore, we have demonstrated that ANG IIinduced hypertension in males is blocked by central infusions of the androgen receptor antagonist, flutamide, and by central infusions of the superoxide dismutase mimetic, tempol. We have also found that, in comparison to females, males show greater levels of intracellular reactive oxygen species in circumventricular organ neurons following long-term ANG II infusions. In female mice, ovariectomy, central blockade of estrogen receptors or total knockout of estrogen α receptors augments the pressor effects of ANG II. Finally, in females but not in males, central blockade of nitric oxide synthase increases the pressor effects of ANG II. Taken together, these results suggest that sex differences and estrogen and testosterone play important roles in the development of ANG II-induced hypertension.

show abstract

“…Implantable mouse BP transmitters (TA11PA-C20; Data Sciences International, St Paul, MN, USA) were used to directly measure arterial pressure in individual conscious and freely moving mice [28,29]. The mice were anaesthetised and the left carotid artery was isolated.…”

Section: Methodsmentioning

confidence: 99%

Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice

et al. 2006

View full text Add to dashboard Cite

Aims/hypothesis In the current study, the effect of a highly specific peptide inhibitor of glycogen synthase kinase 3 (GSK3) (L803-mts) on glucose metabolism and BP was examined in a high-fat (HF) fed mouse model of diabetes. Methods C57/BL6J mice were placed on an HF diet for 3 months and treated with L803-mts for 20 days, following which glucose metabolism was examined by euglycaemichyperinsulinaemic clamp studies. BP and heart rate were measured by radio-telemetry. Results The HF mice were obese, with impaired glucose tolerance and high plasma insulin and leptin levels. L803-mts treatment significantly reduced the insulin levels and doubled the glucose infusion rate required to maintain a euglycaemic condition in the HF+L803-mts group compared with the HF group. Insulin failed to suppress the endogenous glucose production rate in the HF group while decreasing it by 75% in the HF+L803-mts group, accompanied by increased liver glycogen synthase activity and net hepatic glycogen synthesis. GSK3 inhibition also reduced peripheral insulin resistance. Plasma glucose disappearance rate increased by 60% in the HF+L803-mts group compared with the HF group. In addition, glucose uptake in heart and gastrocnemius muscle was markedly improved. Although mean arterial pressure increased following the HF diet, it did not change significantly during the 12 days of L803-mts treatment. Conclusions/interpretation These studies demonstrate that GSK3 inhibition improved hepatic and peripheral insulin resistance in a mouse model of HF-induced diabetes, but it failed to have an effect on BP. GSK3 may represent an important therapeutic target for insulin resistance.

show abstract

Sex differences in the development of angiotensin II-induced hypertension in conscious mice

Cited by 222 publications

References 71 publications

Role of asymmetric dimethylarginine for angiotensin II-induced target organ damage in mice

Role of asymmetric dimethylarginine for angiotensin II-induced target organ damage in mice

Sex differences in angiotensin II- induced hypertension

Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice

Contact Info

Product

Resources

About