Korean J Physiol Pharmacol.  2014 Oct;18(5):411-418. 10.4196/kjpp.2014.18.5.411.

Aortic Remodelling in Chronic Nicotine-Administered Rat

• Zainalabidin S
• Budin SB
• Ramalingam A
• Lim YC

• KMID: 2285540
• DOI: http://doi.org/10.4196/kjpp.2014.18.5.411

Abstract

Vascular remodelling is an adaptive mechanism, which counteracts pressure changes in blood circulation. Nicotine content in cigarette increases the risk of hypertension. The exact relationship between nicotine and vascular remodelling still remain unknown. Current study was aimed to determine the effect of clinically relevant dosage of nicotine (equivalent to light smoker) on aortic reactivity, oxidative stress markers and histomorphological changes. Twelve age-matched male Sprague-Dawley rats were randomly divided into two groups, i.e.: normal saline as control or 0.6 mg/kg nicotine for 28 days (i.p., n=6 per group). On day-29, the rats were sacrificed and the thoracic aorta was dissected immediately for further studies. Mean arterial pressure (MAP) and pulse pressure (PP) of nicotine-treated vs. control were significantly increased (p<0.05). Nicotine-treated group showed significant (p<0.05) increase tunica media thickness, and decrease in lumen diameter, suggesting vascular remodelling which lead to prior hypertension state. The phenylephrine (PE)-induced contractile response in nicotine group was significantly higher than control group (ED50=1.44x10(5) M vs. 4.9x10(6) M) (p<0.05~0.001). However, nicotine-treated rat showed significantly lower endothelium-dependent relaxation response to acetylcholine (ACh) than in control group (ED50=6.17x10(7) M vs. 2.82x10(7) M) (p<0.05), indicating loss of primary vascular function. Malondialdehyde (MDA), a lipid peroxidation marker was significantly higher in nicotine group. Superoxide dismutase (SOD) enzymatic activity and glutathione (GSH) were all reduced in nicotine group (p<0.05) vs. control, suggesting nicotine induces oxidative imbalance. In short, chronic nicotine administration impaired aortic reactivity, probably via redox imbalance and vascular remodelling mechanism.

Keyword

Aorta; Nicotine; Oxidative Stress; Reactivity; Remodelling

MeSH Terms

Acetylcholine
Animals
Aorta
Aorta, Thoracic
Arterial Pressure
Blood Circulation
Blood Pressure
Glutathione
Humans
Hypertension
Lipid Peroxidation
Male
Malondialdehyde
Nicotine
Oxidation-Reduction
Oxidative Stress
Phenylephrine
Rats*
Rats, Sprague-Dawley
Relaxation
Superoxide Dismutase
Tobacco Products
Tunica Media
Acetylcholine
Glutathione
Malondialdehyde
Nicotine
Phenylephrine
Superoxide Dismutase

Figure

• 

  Fig. 1 Cumulative-response curves to phenylephrine and acetylcholine in thoracic aorta ring of control and nicotine groups. (A) PE-induced contractile response in nicotine administered rats showed to be significantly elevated compared to control (B) Nicotine significantly reduced ACh-induced relaxation. Values are means±SEM (n=6). *p<0.05 and **p<0.001 vs. control.

• 

  Fig. 2 Oxidative stress markers and antioxidant levels in the aortas of control vs. nicotine rats. (A) Nicotine group showed higher degree of lipid peroxidation. (B) SOD activity was lowered in nicotine-treated rats. (C) Nicotine significantly reduced the intracellular antioxidant, GSH level. Values are means±SEM (n=6). *p<0.05 and **p<0.001 vs. control.

• 

  Fig. 3 The histological features of H&E stained sections of aorta from control and nicotine groups. (A) Control group displays normal histology of aorta as indicated by regular arrangement of elastic lamella at tunica media layer. (B) Nicotine group showed disorganized tunica media layer with increase in interlamellar space. L, lumen; TI, tunica intima; TM, tunica media; TA, tunica adventitia. Same magnification applied to both pictures (Magnification: 400×).

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