AJH
1991;
4:289-290
Atrial Natriuretic Peptide Lowering Eff< :t of Antihypertensives in Patients With Essential Hypertension
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© 1991 by the American Journal of Hypertension,
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The blood pressure of the patients in b o t h groups during the run-in period w a s greater t h a n 160 m m H g for the systolic a n d 95 m m H g for the diastolic pressure, meeting the criteria for established hypertension. Age, gender ratio, a n d blood pressure w e r e comparable in b o t h groups, A a n d B. There w a s n o significant correla tion b e t w e e n the plasma A N P concentrations a n d the blood pressure at the beginning. Systolic a n d diastolic blood pressures in b o t h groups w e r e significantly d e creased after the treatment with the t w o indicated drugs. Figure 1A s h o w s the plasma A N P levels in a n individual patient before a n d after treatment with C a p topril. After treatment o n a daily dose of 37.5 m g C a p t o pril, plasma A N P concentrations w e r e lowered in all b u t t w o of the ten patients (from 28.2 ± 16.4 to 16.9 ± 6.9 p g / m L (P < .01)). Figure IB s h o w s that treatment with 30 m g nifedipine daily p r o d u c e d a similar reduction in the plasma A N P concentrations in all b u t t w o of the ten patients (from 33.1 ± 21.9 to 20.5 ± 5.6 p g / m L (P < .01)). In contrast, t h e changes in blood pressure a n d those in A N P in response to antihypertensive therapy did not s h o w a n y correlation in either group. The present results clearly d e m o n s t r a t e d that plasma A N P levels were reduced after concomitant effective reduc tion of the blood pressure with either nifedipine or C a p topril. Several studies h a v e reported o n t h e circulating A N P levels in patients with essential hypertension, b u t t h e results h a v e b e e n i n c o n s i s t e n t . We h a v e found that plasma A N P concentrations in hypertensive patients t e n d e d to b e higher b u t did not differ significantly from those in normotensive individuals (unpublished obser vation). The effects of antihypertensive drugs o n plasma A N P concentration h a v e also b e e n a matter of contro versy. It w a s reported in one study that the antihyper tensive therapy did not alter the plasma A N P concen tration, while a substantial reduction in the plasma A N P level consequent to blood pressure reduction w a s reported e l s e w h e r e . Such discrepancies m a y d e p e n d on the m a g n i t u d e of the reduction in blood pressure or o n differences in the drugs used, t h e duration of treat ment, or the patient population. Some studies included subjects with long-standing hypertension w h o m a y h a v e h a d ventricular dysfunction a n d abnormally high A N P levels d u e to this complication, a factor which could not be ruled out. The procedure w e used for selec tion of our subjects unequivocally ruled out this possibil ity. It is n o t e w o r t h y that t w o patients out of the 20 in the present study h a d exceptionally high levels of A N P 3-7
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Atrial natriuretic peptide (ANP) is a potent natriuretic a n d vasoactive substance w h i c h is secreted from the atria of the heart. The plasma concentration of A N P h a s been reported to be elevated in certain cardiovascular disease states, such as heart failure a n d paroxysmal atrial tachycardia. In h u m a n hypertension, the plasma levels of A N P h a v e been reported to be e l e v a t e d or comparable to those of n o r m o t e n s i v e s . Despite in tense efforts, the significance of this h o r m o n e in the pathophysiology of primary hypertension still remains unclear. The last t w o decades h a v e witnessed a burst of p r o gress in n e w antihypertensive agents a n d subsequent changes of antihypertensive regimens. Angiotensin converting e n z y m e (ACE) inhibitors a n d Ca-antagonists h a v e come to be widely used because of their good efficacy a n d low incidence of side effects. However, the changes in plasma A N P levels after a n effective reduc tion in systemic blood pressure by use of such p h a r m a cologic agents h a v e not been fully investigated. Therefore, w e studied changes in circulating levels of immunoreactive a - A N P in patients with uncomplicated essential hypertension both before a n d after the arterial blood pressure w a s reduced by treatment with either the ACE inhibitor, Captopril, or the Ca-antagonist, nifedi pine. A total of 20 outpatients with uncomplicated essential hypertension ( W H O stage 1) were enrolled in this study and were examined a n d diagnosed at our institution. To select those w h o satisfied our inclusion criteria, w e a p plied a list of exclusion criteria, including the presence of left ventricular dysfunction, coronary artery disease, car diac h y p e r t r o p h y , diabetes mellitus a n d other compli cations. G r o u p A consisted of 10 patients w h o were given a daily dose of 37.5 m g of Captopril, a n d group Β consisted of 10 patients w h o were given a daily dose of 30 m g of nifedipine for 4 to 6 m o n t h s . N o n e of the subjects h a d been treated with an antihypertensive m e d ication prior to this trial. All patients remained on ad libitum sodium intake throughout the study period, al t h o u g h they were given general advice regarding smok ing, drinking, weight reduction, a n d salt restriction. Clinical a n d laboratory examinations were carried out both at the beginning a n d e n d of the study period. Blood for determination of the A N P level w a s with d r a w n from an arm vein while the patients were seated. The blood samples were centrifuged, a n d the plasma was stored at — 30 °C until use. A N P levels were deter mined by a radioimmunoassay specific for a - A N P .
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plasma A N P concentrations were decreased after treat m e n t with either Captopril or nifedipine, in association with an effective reduction in arterial blood pressure. We feel that this effect m a y b e d u e to the beneficial effect of antihypertensive therapy on disturbed body fluid homeostasis in patients with hypertension. REFERENCES
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concentrations c o m p a r e d to the rest. The underlying reason for this is unclear, b u t it m a y relate to the hetero geneity of the pathogenesis of essential hypertension. We are so far u n a w a r e of a n y reports of a p h a r m a c o logical effect of concurrent antihypertensive drug ther apy on A N P production. Studies of the role of A N P h a v e suggested that elevated levels of circulating A N P could be a compensatory m e c h a n i s m to ameliorate the volume overload in patients with heart failure or liver disease. This m a y hold true for patients with h y p e r t e n s i o n . ' In this regard, it m a y be a s s u m e d that the effect of antihypertensives on A N P levels is not only a reflec tion of the effect of lowered blood pressure but also a result of the correction of disturbed b o d y fluid h o m e o stasis. The precise m e c h a n i s m causing a reduction of A N P levels in our subjects remains u n d e t e r m i n e d ; fur ther studies are indicated accordingly. In conclusion, the present study demonstrated that 8
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FIGURE 1. Plasma atrial natriuretic peptide (ANP) concentra tions in individual patients before and after treatment with anti hypertensive agents. (A), patients treated with Captopril at a daily dose of 37.5 mg (n = 10); (B), patients treated with nifedipine at a daily dose of 30 mg(n = 10). The reduction of ANP levels observed in both groups was statistically significant by the paired t test (P