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

Abstract EN

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 (NNT) served as control ; Hypertensive non-treated group (HNT) ; Hypertensive LOS-treated group (HLT) administered p.

o.

with LOS (40 µg / kg / d) ; 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 µg / 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 per oxidation 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 nor epinephrine (NE), endothelium-dependent vasodilator acetylcholine (ACh), and endothelium-independent vasodilator sodium nitroprusside (SNP).

Dex injection significantly induced HT (HNT rats) associated with decreased ThW and BW gain, increased VR of aortic rings to NE with attenuated relaxation response to ACh but not to SNP, decreased V with increased R, decreased aortic tissue SOD, GPx and CAT, decreased plasma NOx and GSH, and increased MDA.

HLT rats showed significantly attenuated Dex-induced effects on all tested parameters, except its decreasing effect on Thw, when compared with the corresponding values in HNT 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, aortic 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 ant oxidative properties, can improve Dex-induced endothelial dysfunction, thus causing endothelium-dependent antihypertensive effect, and (4) there is a positive interaction between LOS and ASA when used concomitantly for treatment of Dex-induced HT in rats.