Aortic wall remodeling in rats with nitric oxide deficiency treated by enalapril or verapamil

Pereira, Leila Maria Meirelles; Bezerra, Daniele Gonçalves; Mandarim-de-Lacerda, Carlos Alberto

doi:10.1016/j.prp.2003.12.008

Cited by 23 publications

(13 citation statements)

References 38 publications

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“…29 Aortic tissue was fixed in 10% formaldehyde/phosphate-buffered saline and embedded in paraffin. After routine histological procedures, crosssections proximal to the first intercostal artery were stained with Victoria blue and Ponceau S and studied under Â200 magnification.…”

Section: Histologymentioning

confidence: 99%

Perivascular fat-mediated vascular dysfunction and remodeling through the AMPK/mTOR pathway in high-fat diet-induced obese rats

et al. 2010

Hypertens Res

117

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Perivascular adipose tissue (PVAT) is implicated in the regulation of vascular function in the physiological state, but the modulatory effect of PVAT on vasculature during obesity is poorly understood. Endothelial nitric oxide synthase (eNOS), AMPactivated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) participate in the regulation of vascular function. We therefore investigated whether PVAT has a potential role through the AMPK/mTOR pathway in obesity-related vascular dysfunction. Wistar rats on a high-fat diet (HFD) for 6 months had higher periaortic fat mass compared with rats on a chow diet (3.31 ± 0.56 vs. 2.34 ± 0.28 g, Po0.05). Obesity-related impairment of endothelium-dependent relaxation of the aorta was markedly attenuated by temporary periaortic fat removal whereas obesity-related enhancement of contractile performance was unaffected. Rats on an HFD had thicker aortic tunica medias (180.06±7.56 vs. 128.14±13.21 lm for rats on a chow diet, Po0.01) and larger periaortic adipocytes than rats on a chow diet (1209.00 ± 62.65 vs. 447.20 ± 21.31 lm 2 , respectively, Po0.01). Furthermore, mesenteric arterial rings incubated with periaortic fat from rats on an HFD demonstrated lower endothelium-dependent relaxation. This effect was absent in mesenteric arterial rings incubated with periaortic fat from rats on a chow diet. Moreover, an HFD led to a downregulation of AMPK and eNOS in the aorta with a concurrent upregulation of mTOR. In a parallel in vitro study, culturing vascular smooth muscle cells with periaortic adipocytes from rats on an HFD reduced the AMPK phosphorylation and increased mTOR phosphorylation, and the latter one was blocked by the incubation of compound C. We conclude that PVAT likely impacts obesity-related vascular dysfunction and remodeling through impairment of eNOS-mediated vasodilatation and the AMPK/mTOR pathway.

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Section: Histologymentioning

confidence: 99%

Perivascular fat-mediated vascular dysfunction and remodeling through the AMPK/mTOR pathway in high-fat diet-induced obese rats

et al. 2010

Hypertens Res

117

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“…As reported, vascular relaxation, remodeling and VSMC apoptosis are highly associated with intracellular Ca 2+ [30], and in VSMC, L-type calcium channels are the main resource of intracellular Ca 2+ . Therefore, this I Ca,L and intracellular Ca 2+ decreasing effect of UCN II may contribute greatly to its VSMC apoptosis inhibition.…”

Section: Discussionmentioning

confidence: 70%

Urocortin II Inhibits the Apoptosis of Mesenteric Arterial Smooth Muscle Cells Via L-type Calcium Channels in Spontaneously Hypertensive Rats

Tao

Zhang

Soong

et al. 2006

Cell Physiol Biochem

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Urocortin (UCN) II, a newly isolated corticotropinreleasing- factor (CRF) related peptide, has been found to have potent cardiovascular protective effects. To investigate the mechanisms of its vascular protective effects, we exposed mesenteric arterial smooth muscle cells (MASMC) from spontaneously hypertensive rats (SHR) to UCN II to observe the change in cell apoptosis using TUNEL assay and measured intracellular calcium concentration ([Ca2+]i) using confocal laser scanning microscope. In addition, effects of UCN II on L-type calcium currents (ICa,L) were also measured using whole-cell patch clamp. Our results showed that UCN II concentration-dependently, but time-independently inhibited cell apoptosis. Astressin 2B, a special CRF 2 receptor antagonist, had no influence on this inhibition. Hypoxia or Bay K8644, the L-type calcium channel activator, induced the apoptosis of MASMC from SHR. Pretreatment of the cells with UCN II diminished the effects of hypoxia or Bay K8644. UCN II was also observed to reduce [Ca2+]i increase induced by KCl or Bay K8644. UCN II concentration-dependently inhibited ICa,L, which was not affected by astressin 2B. It did not affect the activation of ICa,L, but markedly shifted the inactivation curve to the left. In conclusion, UCN II inhibits the apoptosis of MASMC from SHR via inhibiting L-type calcium channels.

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“…Large arteries exhibit increased lumen size and media thickening by compromise smooth muscle cells and elastic lamellae (Aguila et al, 2004;Pereira et al, 2004). In small arteries, particularly in mild hypertension, smooth muscle cells are restructured around a smaller lumen, without true hypertrophy (eutrophic remodeling) (Mulvany, 1990(Mulvany, , 2003.…”

Section: Discussionmentioning

confidence: 99%

“…The descending thoracic aorta and the superior mesenteric artery (at level of the first jejunal branch) were excised and then immersed in the same fixative for 24 h. In both arteries, two rings were perpendicularly cut and placed on the cut surface, embedded in Paraplast plus (Sigma-Aldrich Co., St. Louis, MO, USA), and cut at 3 µm thick sections (in aorta, vertical section was obtained according to the previously described) (Pereira et al, 2004). The sections were stained with trichrome methods (Masson and picro sirius red) staining collagen fibers, smooth muscle and nuclei.…”

Section: Estimates Of Relative Variance (= Variance/mean 2 = [Coefficmentioning

confidence: 99%

Beneficial Effects of Angiotensin II AT1 Blocker on Cardiovascular Adverse Remodeling Due to Nitric Oxide Synthesis Blockade

Fernandes-Santos

Mandarim-de-Lacerda

2006

Int. J. Morphol.

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FERNANDES-SANTOS SUMMARY:We studied with morphological tools the effects of different doses of Losartan upon the cardiovascular remodeling in nitric oxide deficient rats. At 15 weeks of age, thirty Wistar rats were separated in six groups: control (C), L-NAME (LN), and four groups were LN was given plus Losartan at different doses (1, 5, 20 and 40 mg/kg/day). The L-NAME was given for 9 weeks, the Losartan administration starting on the 2nd week of experiment. We studied the heart, thoracic aorta and superior mesenteric artery with light microscopy and stereology. The blood pressure (BP) increased since the first week of L-NAME administration, the Losartan treatment at doses of 20 and 40 mg/kg/day was efficient to reduce BP after the 7th week of treatment. The cardiac adverse remodeling in the LN group was characterized by intense interstitial fibrosis, impairment of the myocardial microvascularization, cardiomyocyte hypertrophy and consequent loss of cardiomyocytes. The aortic wall structure (density per area of smooth muscle cell nuclei and surface density of lamellae), and the superior mesenteric artery media/lumen ratio were also strongly affected by L-NAME administration. Only in the dose equal or higher than 20 mg/kg/day Losartan showed beneficial effects treating these alterations. In conclusion, both the heart and the arterial wall of NO deficient rats suffer a marked adverse remodeling process that is efficiently treated by a dose-dependent Losartan administration. The efficiency of Losartan treatment in this model of NO synthesis blockade correlates with the hypotensor effect of the drug mainly in the high dose treatment.

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Aortic wall remodeling in rats with nitric oxide deficiency treated by enalapril or verapamil

Cited by 23 publications

References 38 publications

Perivascular fat-mediated vascular dysfunction and remodeling through the AMPK/mTOR pathway in high-fat diet-induced obese rats

Perivascular fat-mediated vascular dysfunction and remodeling through the AMPK/mTOR pathway in high-fat diet-induced obese rats

Urocortin II Inhibits the Apoptosis of Mesenteric Arterial Smooth Muscle Cells Via L-type Calcium Channels in Spontaneously Hypertensive Rats

Beneficial Effects of Angiotensin II AT1 Blocker on Cardiovascular Adverse Remodeling Due to Nitric Oxide Synthesis Blockade

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