Reduced activity of the kallikrein–kinin system predominates over renin–angiotensin system overactivity in all conditions of sodium balance in essential hypertensives and family-related hypertension

OBJECTIVE: To study the renin-angiotensin-aldosterone and kallikrein-kinin systems in essential hypertensives and offspring of hypertensive parents during different sodium loads, and to explore their possible influence on renal hemodynamics. METHODS: Forty-five essential hypertensives (35 +/- 4 years old, 25 males), 30 offspring of hypertensive parents (26 +/- 8 years old, 16 males) and 30 normotensive controls (28 +/- 5 years old, 20 males) were submitted to three different sodium loads (high, 250 mmol/l; normal, 140 mmol/l; and low, 20 mmol/l). Blood pressure, plasma renin activity, serum aldosterone, total kallikrein and urinary kallikrein-like activity were measured after each period. Effective renal plasma flow and glomerular filtration rate were also measured. In essential hypertensive subjects, renal hemodynamic and hormonal parameters were also measured after 3 days of 20 mg enalapril administration. RESULTS: Plasma renin activity and serum aldosterone were higher in normotensives, essential hypertensives and offspring of hypertensive parents only during low sodium intake, whereas urinary kallikrein activity was lower in hypertensive offspring and essential hypertensives, compared with normotensives, during the three diet conditions. Effective renal plasma flow was found to be reduced in hypertensives and normotensive offspring, while the glomerular filtration rated was similar in the three groups. Angiotensin converting enzyme inhibitor (ACEI) administration to essential hypertensives for 3 days normalized effective renal plasma flow, increased plasma renin activity and decreased aldosterone and urinary kallikrein activity. CONCLUSIONS: Our observations confirmed the presence of a hormonal imbalance between the renin-angiotensin-aldosterone system and the kallikrein-kinin system, not only in essential hypertensives but also in the offspring of hypertensive parents. This imbalance probably affects the renal circulation and sodium homeostasis, since there was reduced effective renal plasma flow in both populations compared with normotensive subjects. The positive effect of ACEI, resulting in normalization of the effective renal plasma flow in essential hypertensive patients, suggests the involvement of both systems in impaired renal circulation.