Differential effects of antihypertensive drugs on neurohormonal activation: Insights from a population-based sample

Objectives. The clinical course of hypertension or heart failure may be modified by the extent of concurrent neurohormonal activation. Factors that regulate neurohormones in patients with these conditions are complex. In the present study, we examined the relative contribution of antihypertensive therapy to the variability of neurohormonal levels in a well defined population based sample. Design and setting. Cross-sectional study of a mixed urban and rural population. Subjects. Middle-aged individuals (n = 646) were analysed in order to elucidate determinants of neurohormone levels by uni- and multivariate comparisons. The assessment included anthropometric, echocardiographic and, if appropriate, genotype information. Results. The intake of antihypertensive drugs was related to significant alterations of neurohormone levels that, in part, exceeded the contribution of all other variables studied. Multivariate analyses revealed that renin levels were independently related to the intake of beta blockers (n = 80;-8.4 mU L^-1: P = 0.001), angiotensin-converting enzyme (ACE)inhibitors (n = 39; +1529 mU L^{- 1}; P = 0.0001), diuretics (n = 62; +14.3 mU L^-1; P = 0.0001), and calcium channel blockers (n = 45: +5.9 mU L^-1; P = 0.05). Aldosterone levels were related to ACE-inhibition (-156.5 pmol L^-1; P = 0.04) and diuretic treatment (+422.4 pmol L^-1; P = 0.0001) in an opposite fashion whereas beta blockers and calcium channel blockers had no significant independent effects. The levels of the atrial natriuretic peptide were significantly related to the use of beta blockers (+ 3.9 pmol L^-1; P = 0.002) and calcium channel blockers (+3.1 pmol L^-1; P = 0.05). Finally, serum angiotensinogen levels and ACE activity were not found to be significantly affected by antihypertensive medication but were rather related to gender or genotype. Conclusions. The data emphasize that antihypertensive treatment with different classes of drugs may modulate serum levels of neurohormones substantially resulting in distinct patterns of activation. These drug- related effects may require consideration when neurohormonal activation is of functional relevance or when neurohormones serve as prognostic predictors in patients with cardiovascular disorders.