Aim: To determine the concentrations of nitric oxide (NO) in plasma of women with essential hypertension in prehypertensive phase, its effect on blood pressure, and correlation with other vasoactive substances that regulate systemic and renal vascular tonus.

Methods: The study performed at the Department of Nephrology, Hospital Center in Skopje, Macedonia, included 26 women with essential hypertension in prehypertensive phase and 11 normotensive women as healthy controls. Vasodilating factors NO and 6-keto-prostaglandin F1 alpha (6-keto-PGF1alpha) were determined in plasma. Thromboxane B2 (TXB2) as a vasoconstricting factor and electrolytes Na+, K+, and Ca2+ were determined in urine. Blood pressure was monitored over 24 hours. Systolic, diastolic, mean blood pressure were presented as average 24-hour values.

Results: The concentrations of NO and 6-keto-PGF1alpha were significantly lower in women with essential hypertension in prehypertensive phase than in their normotensive controls (NO: median 22, range 11-35 vs median 37.5, range 11-66; 6-keto-PGF1alpha: 64.8+/-14.35 vs 98.21+/-43.45 micromol/L; P<0.001). The index of vascular reactivity (TXB2/6-keto-PGF1alpha ratio) was higher in women in prehypertensive phase than in normotensive women (1.3 vs 0.8, P<0.001). Urinary calcium to creatinine ratio was significantly lower in the prehypertensive group (0.06+/-0.03 vs 0.24+/-0.13, P<0.001). No direct correlations were found between NO, TXB2, and 6-keto-PGF1alpha, or between NO and electrolytes in the urine. Low NO and urinary Ca2+ were significant indicators of increased blood pressure (P=0.013 and P=0.024, respectively; backward stepwise multiple regression analysis).

Conclusions: NO and 6-keto-PGF1alpha were significantly lower in women in prehypertensive phase of essential hypertension. Lower NO correlated with increased systolic blood pressure, but not with on natriuresis and calciuresis. These findings, together with the higher vascular reactivity index, indicate that endothelial dysfunction precedes the establishment of essential hypertension.

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