[PP.31.08] CHRONIC INHIBITION OF TWO CONSTITUTIVE NO-SYNTHASE ISOFORMS DURING DEVELOPMENTAL STAGE OF HYPERTENSION

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Abstract

Objective:

The specific effect of endothelial (eNOS) and neuronal (nNOS) NO-synthase on cardiovascular system was confirmed in young and adult normotensive rats. During the prehypertensive period, information related to a long-term nitric oxide (NO) inhibiton is incomplete (eNOS) or completely missing (nNOS). The aim of this study was to investigate the effect of chronic inhibition of constitutive NO-synthase isoforms on cardiovascular system of 4-weeks-old spontaneously hypertensive rats (SHR).

Design and method:

4-weeks-old SHR were treated by 7-nitroindazole (7-NI, specific inhibitor of nNOS, 10 mg/kg/day) or NG-nitro-L-argine methylester (L-NAME; non-specific inhibitor of NOS, 50 mg/kg/day, p.o.) during 6 weeks. Systolic blood pressure (sBP) was measured by the plethysmographic method. The vasoactive responses of thoracic aorta (TA) and mesenteric artery (MA) were measured as changes in isomentric tension. NOS activity was measured in TA using radioactive assay.

Results:

After treatment with 7-NI the sBP was unchanged, the treatment with L-NAME initiated an increase of sBP in the 4th week of the experiment. The contractile responses were signifcantly increased in both experimental groups. Regarding the L-NAME group the increased contractility was associated with increased sensitivity of adrenergic receptors whereby in 7-NI group an increase of absolute contration was observed. After treatment of L-NAME the contractile responses of MA were decreased as the result of the collapse of the contractile apparatus, the treatment with 7-NI did not affect these responses. The long-term NO inhibition induced no (7-NI) or only a slight (L-NAME) inhibitory effect on endothel-depentent relaxation to acetylcholine (ACh). NOS acitivity was decreased by 50% in both experimental groups. However, an acute administration of L-NAME induced not only an increased adrenergic vasoconstriction but also an inhibition of acetylcholine-evoked vasorelaxation proving a well-preserved production of NO in all followed groups.

Conclusions:

Results confirmed the specificity of nNOS a eNOS signalization in prehypertensive SHR as well heterogenity in vasoactive responses of elastic (HA) and muscular (MA) types of arteries. HA disposes of compensatory mechanisms in condition of non-specific NO deficiency: adaptive contractile abilities assosiated with activation of NO-derived vasorelaxation which could later compensate effect of sympatic nervous system. Supported by VEGA-2/0074/14; VEGA-2/0067/14; MZ-2012/51-SAV-1.

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