DIFFERENTIAL-EFFECTS OF ANTIHYPERTENSIVE DRUGS ON NEUROHORMONAL ACTIVATION - INSIGHTS FROM A POPULATION-BASED SAMPLE

Objectives. The clinical course of hypertension or heart failure may b e modified by the extent of concurrent neurohormonal activation. Facto rs that regulate neurohormones in patients with these conditions are c omplex. In the present study, we examined the relative contribution of antihypertensive therapy to the variability of neurohormonal levels i n a well defined population based sample. Design and setting. Cross-se ctional study of a mixed urban and rural population. Subjects. Middle- aged individuals (n = 646) were analysed in order to elucidate determi nants of neurohormone levels by uni- and multivariate comparisons. The assessment included anthropometric, echocardiographic and, if appropr iate, genotype information. Results. The intake of antihypertensive dr ugs was related to significant alterations of neurohormone levels that , in part, exceeded the contribution of all other variables studied. M ultivariate analyses revealed that renin levels were independently rel ated to the intake of beta blockers (n = 80; -8.4 mU L-1; P = 0.001), angiotensin-converting enzyme (ACE)-inhibitors (n = 39; +15.9 mU L-l; 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 diureti c treatment (+422.4 pmol L-1; P = 0.0001) in an opposite fashion where as beta blockers and calcium channel blockers had no significant indep endent effects. The levels of the atrial natriuretic peptide were sign ificantly related to the use of beta blockers (+3.9 pmol L-1; P = 0.00 2) and calcium channel blockers (+3.1 pmol L-1; P = 0.05). Finally, se rum angiotensinogen levels and ACE activity were not found to be signi ficantly affected by antihypertensive medication but were rather relat ed to gender or genotype. Conclusions. The data emphasize that antihyp ertensive 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 wh en neurohormonal activation is of functional relevance or when neuroho rmones serve as prognostic predictors in patients with cardiovascular disorders.