Effects of angiotensin converting enzyme inhibitors and calcium antagonists on atrial natriuretic peptide release and action and on albumin excretion rate in hypertensive insulin-dependent diabetic patients.
Abnormalities in sodium homeostasis and in atrial natriuretic peptide (ANP) behavior could play a role in determining and accelerating the development of glomerular hypertension, hypertension, and microalbuminuria in insulin-dependent diabetes. The aim of the present study was to investigate in 32 hypertensive insulin-dependent diabetic patients (HD) with an altered albumin excretion rate the natriuretic response and ANP release to saline load (2 mmol/kg 90 min, and the effects angiotensin converting enzyme inhibitor therapy 2.5 to 5.0 mg cilazapril, once daily), and calcium antagonists (sustained release verapamil: 120 to 240 mg Isoptin Press, once daily, and long acting nifedipine: 20 to 40 mg Adalat AR, twice daily) on sodium homeostasis and albumin excretion rate. Eight normal subjects matched for sex, age, and weight served as controls. The 32 HD patients showed a blunted response in ANP release and sodium excretion during saline infusion in comparison with controls. The cilazapril and verapamil treatments were tested in 16 of the 32 HD patients and were both effective in ameliorating natriuretic and ANP response to saline load and in decreasing albumin excretion rate. The combined cilazapril and verapamil treatment further improved both these parameters in these patients, although blood pressure levels were comparable. The other 16 HD patients underwent sequential verapamil and nifedipine treatment. Verapamil was more effective than nifedipine in improving natriuresis and ANP release to saline load and in lowering the albumin excretion rate. The results of the present study demonstrate that sodium homeostasis and ANP release are altered in hypertensive nephropathic patients, and both cilazapril and verapamil are more effective than nifedipine in ameliorating natriuresis, ANP release, and albumin excretion rate.
Fioretto
P
P
Istituto di Medicina Interna, Policlinico Universitario, Padova, Italy.
Frigato
F
F
Velussi
M
M
Riva
F
F
Muollo
B
B
Carraro
A
A
Brocco
E
E
Cipollina
M R
MR
Abaterusso
C
C
Trevisan
M
M
D000328:Adult; D000419:Albuminuria; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000378:metabolism* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D017315:Cilazapril / Q000494:pharmacology / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use; D012965:Sodium Chloride / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D017315:Cilazapril; D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor; D014700:Verapamil; D009543:Nifedipine