Abstract

Although the role of nitric oxide (NO) in essential hypertension is still unclear, the effects of long-term NO deficiency have not yet been investigated during the critical juvenile period in spontaneously hypertensive rats (SHR). We aimed to analyze the effects of chronic NO synthase (NOS) inhibition on systolic blood pressure (sBP), vasoactivity, morphological changes and superoxide level in the thoracic aorta (TA), NOS activity in different tissues, and general biomarkers of oxidative stress in plasma of young SHR. Four-week-old SHR were treated with NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day, p.o.) for 4-5 weeks. L-NAME treatment induced a transient sBP increase only, and surprisingly, slightly inhibited endothelium-dependent relaxation of TA. Hereby, the inhibition of NOS activity varied from tissue to tissue, ranging from the lowest in the TA and the kidney to the highest in the brain stem. In spite of an increased sensitivity of adrenergic receptors, the maximal adrenergic contraction of TA was unchanged, which was associated with changes in elastin arrangement and an increase in wall thickness. The production of reactive oxygen species in the TA was increased; however, the level of selected biomarkers of oxidative stress did not change. Our findings proved that the TA of young SHR responded to chronic NO deficiency by the development of adaptive mechanisms on the functional (preserved NO-derived vasorelaxation, unincreased contraction) and molecular (preserved NOS activity) level.

Highlights

  • An increase in the systolic blood pressure evoked by reduced production of endogenous nitric oxide (NO) after NO synthase (NOS) inhibition has been already considered as a uniform response of the cardiovascular system

  • Increased systolic blood pressure (sBP) is developed gradually in spontaneously hypertensive rats (SHR); in 3–5-week-old SHR, it does not differ from the age-matched normotensive rats

  • Chronic L-NAME treatment in young SHR induced a transient increase in sBP in the 3rd week of treatment

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Summary

Introduction

An increase in the systolic blood pressure (sBP) evoked by reduced production of endogenous nitric oxide (NO) after NO synthase (NOS) inhibition has been already considered as a uniform response of the cardiovascular system. Increased vasoconstriction and oxidative stress, impaired endothelium-dependent vasorelaxation, and abnormal cardiovascular remodeling accompanied by arterial wall hypertrophy are the main hallmarks of these two experimental models [2]. Several studies speculated that the cause is a Oxidative Medicine and Cellular Longevity disturbed endogenous NO production and/or the decreased endothelium-derived vasorelaxation in certain arteries within the blood bed [3, 4]. Other studies confirmed the potentiation of NO-dependent relaxation associated with an increased NO production by the vessel wall during developed essential hypertension [5, 6]. The overproduction of superoxides, found in adult SHR, could lead to the decrease of NO bioavailability [7]

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