Non-modulating hypertension: evidence for the involvement of kallikrein/kinin activity associated with overactivity of the renin-angiotensin system. Successful blood pressure control during long-term Na+ restriction.

ABSTRACT

BACKGROUND: Non-modulating hypertensives are a subset of sodium-sensitive hypertensives characterized by a failure to modulate renal, vascular and adrenal glomerulosa responsivenesses to angiotensin II appropriately. OBJECTIVE: To investigate the plasma renin activity (PRA) and urinary kallikrein-like activity (Ku) under different sodium conditions in essential hypertensive patients and in the modulating and non-modulating subsets of hypertensives. Additionally, in these groups of patients, the effects on blood pressure of a sustained Na+ restriction were evaluated. METHODS: Fifteen normotensives (10 men, aged 29 +/- 5 years) and 54 untreated hypertensives (30 men, aged 34 +/- 7 years) were each administered subsequently three different diets containing 240, 140 and 50 mmol/day Na+, each diet for 10 days. At the end of each period, the PRA, Ku, 24 h urinary volume and urinary Na+ excretion were measured. Afterwards, the essential hypertensives were classified as 29 modulating essential hypertensives (MHT, 20 men, aged 32 +/- 7 years) and 25 non-modulating essential hypertensives (NMHT, 10 men, aged 36 +/- 8 years). Non-modulating ones were identified as individuals who failed to increase their effective renal plasma flow and to decrease their filtration fraction by at least 30% from baseline values, 10 days after changing from a low (10 mmol/day) to a high (260 mmol/day) Na+ intake. Blood pressure was measured with a Dinamap 8100 Critikon device. Both PRA and Ku were measured during normal Na+ intake by standard methods. Patients were administered a low-Na+ diet (10-50 mmol/day) for 12 months. RESULTS: In essential hypertensives, Ku was lower under the three Na+ diets than it was in normotensives (P < 0.01) whereas the PRA was higher in hypertensives only during the low Na+ intake (P < 0.01). The non-modulating patients showed significantly higher PRA levels (4.0 +/- 0.8 ng ml h, P < 0.05) than did modulating ones (2.6 +/- 1.0 ng ml h) or normotensives (2.3 +/- 1.0 ng ml h). Conversely, non-modulating hypertensives had lower Ku (4.1 +/- 1.0 IU/24 h, P < 0.025) than did modulating ones (6.2 +/- 1.0 IU/24 h) or normotensives (7.8 +/- 2.0 IU/24 h). Blood pressure was significantly reduced during low Na+ intake only in normotensives (month 6 143 +/- 4/94 +/- 2 mmHg; month 12 139 +/- 5/89 +/- 3 mmHg) compared with baseline values (169 +/- 4/102 +/- 6 mmHg, P < 0.025). CONCLUSIONS: It was shown that, in non-modulating hypertensives, in addition to an increased PRA, a reduced kallikrein-like activity coexists and seems to be associated with the impaired Na+ handling. Moreover, in these untreated patients the Na+ restriction was able to exert an antihypertensive effect even for long periods.