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D-002 BORDERLINE HYPERTENSION IS ASSOCIATED WITH NITRIC OXIDE-INDEPENDENT ENDOTHELIAL DYSFUNCTION IN FEMORAL ARTERIES OF RATS

Background Borderline hypertensive rat (BHR) is the first filial offspring of spontaneously hypertensive (SHR) dams and normotensive Wistar-Kyoto (WKY) sires and it may serve as an experimental model of human prehypertension and early stage hypertension. This study investigated nitric oxide (NO) production, oxidative load and vascular responses in male, 22-week-old, BHR and age-matched SHR and normotensive WKY rats. Methods Systolic blood pressure (BP) was determined by tail-cuff method. NO production was determined by conversion of [3H]-L-arginine in the aorta. Conjugated dienes and concentrations of thiobarbituric acid-reactive substances were measured in the left ventricle (LV) and kidney (for assessment of oxidative load). Vascular reactivity was investigated in rings of the femoral artery (FA) using a wire myograph. Results BP of WKY, BHR and SHR was 106 ± 2, 143 ± 3 and 191 ± 3 mmHg, respectively (p < 0.01 for each). Significant LV hypertrophy, elevated NO production and oxidative stress in all organs investigated were present in BHR and SHR. Endothelium-dependent relaxation of the FA induced by acetylcholine (ACh) was reduced in both BHR and SHR vs. WKY, however endothelial dysfunction was more pronounced in SHR. The NO-dependent component of ACh-induced relaxation was similar in all groups investigated. However, the NO-independent component of ACh-induced relaxation was reduced significantly in BHR and SHR vs. WKY. Moreover, negative correlation (r = -0.66, p < 0.0004) was observed between NO-independent relaxation and BP. ACh at higher concentrations caused endothelium-dependent contractions in BHR and SHR FA but not in FA from WKY. Conclusions Our study showed that LV hypertrophy, NO-independent endothelial dysfunction and endothelium-dependent contracting factors release in association with oxidative stress were present already in BHR. Thus the results suggest that borderline hypertension may also represent a risk of other cardiovascular diseases as fully developed hypertension. This work was supported by the Slovak Research and Development Agency under the contract No. APVV-0523-10.