Work

Chronic renin inhibition lowers blood pressure and reduces upright muscle sympathetic nerve activity in hypertensive seniors

Year: 2013

Type: article

Abstract: Cardiovascular risk remains high in elderly patients with hypertension even with adequate blood pressure control; one possible mechanism may be sympathetic activation via the baroreflex in response to blood pressure reduction. We found that chronic diuresis increased vasomotor sympathetic activity in both the supine and the upright positions, while chronic renin inhibition did not affect sympathetic activity in the supine position but attenuated its response to head-up tilt in elderly hypertensive patients. The change of sympathetic activity by anti-hypertensive drug treatment was correlated with the change of aldosterone level in all patients. Upright sympathetic baroreflex sensitivity remained unchanged after diuresis or renin inhibition. These results suggest that chronic renin inhibition lowers blood pressure in elderly hypertensive patients without sympathetic activation, in contrast to diuresis which increases sympathetic activity through the augmented renin–angiotensin–aldosterone system. Abstract Cardiovascular risk remains high in patients with hypertension even with adequate blood pressure (BP) control. One possible mechanism may be sympathetic activation via the baroreflex. We tested the hypothesis that chronic inhibition of renin reduces BP without sympathetic activation, but diuresis augments sympathetic activity in elderly hypertensives. Fourteen patients with stage-I hypertension (66 ± 5 (SD) years) were treated with a direct renin inhibitor, aliskiren (n= 7), or a diuretic, hydrochlorothiazide (n= 7), for 6 months. Muscle sympathetic nerve activity (MSNA), BP, direct renin and aldosterone were measured during supine and a graded head-up tilt (HUT; 5 min 30° and 20 min 60°), before and after treatment. Sympathetic baroreflex sensitivity (BRS) was assessed. Both groups had similar BP reductions after treatment (all P < 0.01), while MSNA responses were different between hydrochlorothiazide and aliskiren (P= 0.006 pre/post × drug). Both supine and upright MSNA became greater after hydrochlorothiazide treatment (supine, 72 ± 18 post vs. 64 ± 15 bursts (100 beats)−1 pre; 60° HUT, 83 ± 10 vs. 78 ± 13 bursts (100 beats)−1; P= 0.002). After aliskiren treatment, supine MSNA remained unchanged (69 ± 13 vs. 64 ± 8 bursts (100 beats)−1), but upright MSNA was lower (74 ± 15 vs. 85 ± 10 bursts (100 beats)−1; P= 0.012 for pre/post × posture). Direct renin was greater after both treatments (both P < 0.05), while upright aldosterone was greater after hydrochlorothiazide only (P= 0.002). The change in upright MSNA by the treatment was correlated with the change of aldosterone (r= 0.74, P= 0.002). Upright sympathetic BRS remained unchanged after either treatment. Thus, chronic renin inhibition may reduce upright MSNA through suppressed renin activity, while diuresis may evoke sympathetic activation via the upregulated renin–angiotensin–aldosterone system, without changing intrinsic sympathetic baroreflex function in elderly hypertensive patients.

Source: The Journal of Physiology

DOI: 10.1113/jphysiol.2013.261362