Lacidipine Prevents Endothelial Dysfunction in Salt-Loaded Stroke-Prone Hypertensive Rats

Křenek, Peter; Salomone, Salvatore; Kyselovič, Ján; Wibo, Maurice; Morel, Nicole; Godfraind, Théophile

doi:10.1161/01.hyp.37.4.1124

Cited by 32 publications

(37 citation statements)

References 38 publications

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“…Lacidipine is a calcium-channel blocker of the dihydropiridine class that has been shown to prevent endothelial dysfunction in hypertensive rats (38), restore endotheliumdependent vasodilation in hypertensive patients (39), and decrease oxidative stress (19). In this study, lacidipine reduced endothelin and malondialdehyde production and increased intracellular glutathione levels, although none of the effects induced by exposure of endothelial cells to ethanol were corrected.…”

Section: Discussionmentioning

confidence: 65%

Effects of Antihypertensive Drugs on Alcohol-Induced Functional Responses of Cultured Human Endothelial Cells

et al. 2008

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Section: Discussionmentioning

confidence: 65%

Effects of Antihypertensive Drugs on Alcohol-Induced Functional Responses of Cultured Human Endothelial Cells

et al. 2008

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“…Statistical analysis was performed by ANOVA, followed by Fisher's PLSD test; ‫,ء‬ P Ͻ 0.05 versus control. 1994) and in salt-loaded stroke-prone SHRs (Krenek et al, 2001). Furthermore, chronic nifedipine treatment causes an increase in expression of eNOS messenger RNA in the aorta from stroke-prone SHRs (Naruse et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

High Salt Intake Impairs Vascular Nitric Oxide/Cyclic Guanosine Monophosphate System in Spontaneously Hypertensive Rats

Kagota¹,

Tamashiro²,

Yamaguchi³

et al. 2002

J Pharmacol Exp Ther

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In aortas of spontaneously hypertensive rats (SHRs), excessive dietary salt causes down-regulation of soluble guanylate cyclase (sGC) followed by decreased cyclic GMP production, which leads to impairment of the vascular relaxation response to nitric oxide (NO). The present study aimed to elucidate whether this impaired NO/cyclic GMP system results secondarily from increased blood pressure or from an effect of the salt itself. The antihypertensive drug nifedipine was used on 4-week-old SHRs that received a normal-salt diet or a high-salt diet for 4 weeks. Treatment with nifedipine (30 mg/kg/day, p.o.) reduced the increased blood pressure of SHRs fed the high-salt diet to the level of SHRs fed the normal-salt diet. In aortic rings from SHRs fed the high-salt diet, not only endothelium-dependent relaxations but also endothelium-independent relaxations were significantly impaired. However, these impairments were not alleviated by treatment with nifedipine. Furthermore, nifedipine did not prevent the increase in protein levels of endothelial NO synthase and the decrease in the protein levels of sGC in aortas from SHRs fed the high-salt diet. These alterations by high salt intake were restored after replacement with the normal-salt diet for 4 additional weeks. These results indicate that in SHRs given excessive dietary salt, normalization of salt intake but not blood pressure reduction can ameliorate alterations in the NO/cyclic GMP system. High salt intake may directly affect the vascular smooth muscle and cause impairment of the relaxation response to NO.Nitric oxide (NO), known as an endothelium-derived relaxing factor, is usually generated in the circulation via stimulation of vascular endothelial NO synthase (eNOS) by physical stimuli, such as increase in transmural pressure or blood flow (shear stress) (Rubanyi et al., 1990;Fleming and Busse, 1999). NO, which is released from the endothelium to smooth muscle cells, activates the soluble isoform of guanylate cyclase (sGC) to form cyclic GMP (Lucas et al., 2000). The increased cyclic GMP level causes vascular smooth muscle relaxation. Such a NO/cyclic GMP system regulates vascular tone in various vascular beds (Förstermann et al., 1986;Koesling and Friebe, 1999). Thus, it is widely accepted that NO plays an important role in the pathogenesis of hypertension (Boulanger, 1999).Several vasodilators, including acetylcholine, are known to produce endothelium-dependent relaxations through synthesis/release of NO in the endothelium of various arteries. Many studies have documented that endothelium-dependent relaxations in response to acetylcholine are impaired in the aortas from experimental hypertensive rats, such as aged spontaneously hypertensive rats (SHRs) (Konishi and Su, 1983) and Dahl salt-sensitive rats (Lü scher et al., 1987). Furthermore, treatment with calcium antagonists, drugs commonly used to control hypertension, can prevent endothelial dysfunction in the aortas of adult SHRs (Gray et al., 1993) and Dahl salt-sensitive rats (Boulanger et al., 199...

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“…Previous studies in salt-loaded SHRSP demonstrated that inhibition of NO generation with NOS blockers abolishes Ach-stimulated responses, indicating that Ach-mediated vasodilation depends on endothelium-derived NO in this model. 31 Endothelium-independent relaxation was assessed in norepinephrine-precontracted vessels exposed to sodium nitroprusside ( …”

Section: Study Of Small Arteriesmentioning

confidence: 99%

Antioxidant Effects of Vitamins C and E Are Associated With Altered Activation of Vascular NADPH Oxidase and Superoxide Dismutase in Stroke-Prone SHR

et al. 2001

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Abstract-Ascorbic acid (vitamin C) and ␣-tocopherol (vitamin E) have antioxidant properties that could improve redox-sensitive vascular changes associated with hypertension. We determined whether vitamins C and E influence vascular function and structure in hypertension by modulating activity of NADPH oxidase and superoxide dismutase (SOD). Adult stroke-prone spontaneously hypertensive rats (SHRSP) were divided into 3 groups: control (C; nϭ6), vitamin C-treated (vit C, 1000 mg/day; nϭ7), and vitamin E-treated (vit E, 1000 IU/day; nϭ8). All rats were fed 4% NaCl. Blood pressure was measured weekly. After 6 weeks of treatment, the rats were killed, and mesenteric arteries were mounted as pressurized preparations. Vascular O 2 Ϫ generation and NADPH oxidase activity were measured by chemiluminescence. Vascular SOD activity and plasma total antioxidant status (TAS) were determined spectrophotometrically. Blood pressure increased from 212Ϯ7 to 265Ϯ6 mm Hg in controls. Treatment prevented progression of hypertension (vit C, 222Ϯ6 to 234Ϯ14 mm Hg; vit E, 220Ϯ9 to 227Ϯ10 mm Hg). Acetylcholine-induced vasodilation was improved (PϽ0.05), and media-to-lumen ratio was reduced (PϽ0.05) in the treated rats. O 2 Ϫ was lower in vitamin-treated groups compared with controls (vit C, 10Ϯ4 nmol · min Ϫ1 · g Ϫ1 dry tissue weight; vit E, 9.6Ϯ3.5 nmol · min Ϫ1 · g Ϫ1 dry tissue weight; C, 21Ϯ9 nmol · min Ϫ1 · g Ϫ1 dry tissue weight; PϽ0.05). Both vitamin-treated groups showed significant improvement (PϽ0.01) in TAS. These effects were associated with decreased activation of vascular NADPH oxidase (vit C, 46Ϯ10; vit E, 50Ϯ9; C, 70Ϯ16 nmol · min Ϫ1 · g Ϫ1 dry tissue weight, PϽ0.05) and increased activation of SOD (vit C, 12Ϯ2; vit E, 8Ϯ1; C, 4.6Ϯ1 U/mg; PϽ0.05). Our results demonstrate that vitamins C and E reduce oxidative stress, improve vascular function and structure, and prevent progression of hypertension in SHRSP. These effects may be mediated via modulation of enzyme systems that generate free radicals.

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Lacidipine Prevents Endothelial Dysfunction in Salt-Loaded Stroke-Prone Hypertensive Rats

Cited by 32 publications

References 38 publications

Effects of Antihypertensive Drugs on Alcohol-Induced Functional Responses of Cultured Human Endothelial Cells

Effects of Antihypertensive Drugs on Alcohol-Induced Functional Responses of Cultured Human Endothelial Cells

High Salt Intake Impairs Vascular Nitric Oxide/Cyclic Guanosine Monophosphate System in Spontaneously Hypertensive Rats

Antioxidant Effects of Vitamins C and E Are Associated With Altered Activation of Vascular NADPH Oxidase and Superoxide Dismutase in Stroke-Prone SHR

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