Effect of concomitant administration of aspirin and losartan on endothelium dependent oxidative stress in dexamethasone-induced hypertensive rats

Patients with hypertension [HT] usually take antihypertensive drugs and aspirin [acetylsalicylic acid; ASA]. However, few studies described the physiological effects of interaction of antihypertensive agents with aspirin. Therefore, this study aimed to investigate the effects of losartan [LOS] and/or ASA on dexamethasone [Dex]-induced HT in rats, Forty-five adult male albino rats [216 +/- 23 g] were used and equally divided into 5 groups [n=9]; Normotensive non-treated group [NNflrved as control; Hypertensive non-treated group [HNT]; Hypertensive LOS-treated group [HLT] administered p.o. with LOS [40 mgfkgld]; Hypertensive ASA-treated group [HAT] administered p.o. with ASA [100 mg/kg/d]; and Hypertensive combined LOS-and ASA-treated group [HLA]. The experimental period was 14 days. Hypertension was induced by i.p. injection of Dex [40 jtg/kg/d]. Systolic blood pressure [SBP] and body weight [BW] were measured on alternative days. At the end of experiments, renal blood flow velocity [V] and resistance [R] were measured in anesthetized rats. Rats were then sacrificed and a blood sample, thymus and aortic ring specimen were taken from each rat. Thymuses were weighed [ThW] as markers of Dex activity. Blood samples were used for biochemical analysis [plasma nitric oxide metabolites [NOx], the antioxidant marker reduced glutathione [GSH], and the lipid peroxidation marker malondialdehyde [MDA]]. Each aortic ring was divided into two pieces, one for measurements of tissue antioxidants [superoxide dismutase [SOD], glutathione peroxidase [GPx], and catalase [CAT]], and the other one for aortic vascular reactivity [VR] to norepinephrine [NE], endothelium-dependent vasodilator acetylcholine [ACh], and endotheliumindependent vasodilator sodium nitroprusside [SNP]. Dex injection significantly induced HT [lINT rats] associated with decreased ThW and BW gain, increased yR of aortic rings to NE with attenuated relaxation response to ACh but riot to SNP, decreased V with increased R, decreased aortic tissue SOD, GPx and CAT, decreased plasma NOx and GSH, and increased MDA. JILT rats showed significantly attenuated Dex-induced effects on all tested parameters, except its decreasing effect on Thw, when compared with the corresponding values in lINT rats. Similar, but less prominent attenuation of the Dex-induced effects occurred in HAT rats. Interestingly, the present study showed a statistical positive interaction between ASA and LOS in combination [HLA rats] and LOS or ASA alone, with complete prevention of the Dex-induced effects on SBP, aortjc VR to NE and ACh, V. R, and plasma levels of MDA, NOx and GSH. Moreover, HLA rats showed greater enhancement of aortic tissue GPx and CAT activity compared with HLT and LAT rats. In conclusion, the present study revealed that [1] Dex-induced HT is associated with vascular oxidative stress, [2] the antihypertensive action of LOS is endothelium-dependent and may be mediated via reduction of systemic oxidative stress mediators and enhancement of endothelial antioxidants, [3] aspirin [in the given dose], via its antioxidative properties, can improve Dex-induced endothelial dysfunction, thus causing endothelium-dependent antthypertensive effect, and [4] there is a positive interaction between LOS and ASA when used concomitantly for treatment of Dex-induced HT in rats

Role of folic acid administration in prevention and/or reversal of dexamethasone-induced hypertension in rats

Many forms of hypertension [HT] are associated with increased oxidative stress and vascular endotheliam dysfunction with nitric oxide [NO] deficiency. The aim of the present study was to investigate [1] the implication of homocysteine [Hcy], oxidative stress and NO in the pathophysiology of dexamethasone [Dex]-induced HT in rats; [2] the effect of folic acid [FA], a potent antioxidant, on prevention and/or reversal of Dex-induced HT in rats; [3] the potential beneficial effect of FA on endothelial function. Forty male adult albino rats were used and equally divided into 5 groups [n = 8]; [1] Control group [Con] injected intraperitoneally [i.p.] with saline [1 ml/kg/day] for 13 days [ds]; [2] Folic acid group [FA] orally [p.o.] given FA [20 mg/kg/day] for 13 ds and Lp. injected with saline for the same period; [3] Dex-treated group [Dex] co-treated with Lp. Dex [40 micro g/kg/d] and p.o. saline for 13 ds; [4] FA followed by Dex group [FA+Dex] pretreated with p.o. FA for 4 ds followed by co-treatment with Lp. Dex and p.o. saline for the rest of the 13 ds [prevention study]; [5] Dex followed by FA group [Dex+FA] injected Lp. with Dex for 13 ds, and given p.o. saline for the first 9 ds then p.o. FA for the next 4 ds [reversal study]. Systolic blood pressure [SBP] was measured by tail cuff method. Body weight [BW] and thymus weight [ThW] were measured as markers of Dex activity. Markers ofoxidative stress [lipid peroxidation indicated by malondialdehyde [MDA], NO metabolites [NOx], and reduced glutathione [GSH]] and Hey were determined in rat plasma 13 ds after treatments. Vascular reactivity [VR] of isolated aortic rings [isometric g tension] to norepinephrine [NE], endotheliwn-dependent vasodilator acetylcholine [ACh], and endo-thelium-independent vasodilator sodium nitropmsside [SNP] were measured to assess endothelialfunction. Results of the present investigation showed that Dex-induced HT was accompanied by significantly increased plasma levels of MDA and Hey, decreased plasma levels of NOx and GSH, and increased VR of aortic rings to NE with attenuated relaxation response to ACh but not to SNP. Treatment with FA partially prevented but not reversed Dex-induced effects. FA significantly increased plasma NOx and GSH levels, decreased plasma MDA and Hcy concentrations, and reduced VR of aortic rings to NE when compared to the Dex group levels. Furthermore, FA has beneficial effect on endothelial function via improving endothelium-dependent vasodilatation response to ACh. In conclusion, results of the present study revealed a protective role of FA against Dex-induced HT which could be attributed to the FA ability to decrease associated oxidative stress of the vascular endothelium via decreasing Hey and MDA, and increasing GSH and NO production