atrial-natriuretic-factor and zofenopril

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.

Topics: Antihypertensive Agents; Atenolol; Atrial Natriuretic Factor; Blood Pressure; Captopril; Double-Blind Method; Drug Interactions; Hemodynamics; Humans; Hypertension

In 14 patients with congestive heart failure (CHF) of various grade (NYHA class 2-4) the effects of zofenopril calcium (SQ 26,991) on blood pressure and forearm circulation were studied by venous occlusion plethysmography. Changes in plasma renin activity (PRA), aldosterone, Atrial natriuretic factor (ANF) and arginine-vasopressin (AVP) were also measured. Two hours after oral administration of 7.5 mg of zofenopril we observed a decrease in blood pressure, heart rate, and forearm vascular resistance along with an increase in venous distensibility. Zofenopril also decreased ANP levels in a manner directly related to peripheral venodilatation (r = .64; P less than .05) and modified arginine-vasopressin (AVP) proportionally to the fall in blood pressure observed in response to drug administration (%SBP/%AVP: r = .64, P less than .05; %DBP/%AVP: r = .67, P less than .05). Hemodynamic and humoral responses to zofenopril occurred without any significant unwanted adverse reaction, even in patients with greater pressor reduction. We conclude that oral acute zofenopril administration, in patients with congestive heart failure, causes an arterial and venous forearm vasodilatation which is probably involved in the acute changes in plasma levels of ANF and AVP observed after drug administration.

Topics: Administration, Oral; Aged; Angiotensin I; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Captopril; Female; Forearm; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Renin; Vasodilation; Veins