The effects of atenolol and zofenopril on plasma atrial natriuretic peptide are due to their interactions with target organ damage of essential hypertensive patients.
The effects of 10 weeks of treatment with atenolol (n = 9) or the converting enzyme inhibitor zofenopril (n = 25) on plasma atrial natriuretic peptide (ANP) were studied in 34 essential hypertensive patients. After 4 weeks on placebo, pretreatment ANP, 56 +/- 7 pg/ml, was slightly but not significantly higher than that of 29 controls (41 +/- 4) and correlated with age (r = 0.44), ECG score for left ventricular hypertrophy (LVH) (r = 0.51) and serum creatinine (r = 0.67), and negatively with creatinine clearance (r = -0.39). Atenolol reduced blood pressure (BP) by 0 +/- 6/8 +/- 2 mm Hg (ns/P < 0.01), and zofenopril by 14 +/- 4/6 +/- 2 (P < 0.01/P < 0.01), not significantly different between the two agents. Heart rate was decreased by atenolol (-16 +/- 4 bpm, P < 0.01) but not by zofenopril (+1 +/- 2 bpm, ns). Atenolol increased ANP in all patients but one (delta = +42 +/- 9 pg/ml, P < 0.01), while zofenopril did not change it significantly (-6 +/- 6 pg/ml), due to 15 patients exhibiting decreases and 10 increases in plasma ANP. The effect of atenolol on ANP positively correlated with duration of hypertension (r = 0.74), ECG score for LVH (r = 0.73) and serum creatinine (r = 0.68). Individual changes in ANP by zofenopril negatively correlated with pretreatment ANP (r = -0.69), ECG score for LVH (r = -0.44) and serum creatinine (r = -0.41). No correlations were found between BP, heart rate or their changes by treatment and the effect of either agent on plasma ANP. Multiple linear regression showed that the change in ANP was explained by the therapeutic agent used, the pretreatment plasma level of ANP, and the ECG score for LVH (F = 12.5, P < 0.001, r2 = 0.56). We conclude that the effect of antihypertensives on plasma ANP is independent of their action on BP, but dependent on an interaction between the type of drug employed and those clinical characteristics of the patient that reflect pre-existing hypertensive target organ damage.
Elijovich
F
F
Department of Internal Medicine, University of Texas Medical Branch at Galveston 77555-0566, USA.
Laffer
C L
CL
Schiffrin
E L
EL
D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001262:Atenolol / Q000008:administration & dosage*; D009320:Atrial Natriuretic Factor / Q000097:blood*; D001794:Blood Pressure; D002216:Captopril / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004311:Double-Blind Method; D004347:Drug Interactions; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D000959:Antihypertensive Agents; C044958:zofenopril; D001262:Atenolol; D009320:Atrial Natriuretic Factor; D002216:Captopril