Determinants of the initial effects of captopril on blood pressure, glomerular filtration rate, and natriuresis in mild-to-moderate chronic congestive heart failure secondary to coronary artery disease.
Whereas angiotensin-converting enzyme inhibitors are now indicated for all grades of chronic heart failure, the 2 adverse effects that limit use of these drugs are systemic hypotension and renal dysfunction. The recognized clinical correlates such as hyponatremia and high diuretic dose, which predict occurrence of these adverse effects in severe chronic congestive heart failure (CHF), are rarely evident in patients with mild-to-moderate CHF. Accordingly, we studied 36 patients with stable, moderate CHF in a double-blind, placebo-controlled, crossover fashion to evaluate by multiple discriminate regression analysis the pathophysiologic determinants of changes in blood pressure, glomerular filtration rate, and urinary sodium excretion after initial converting enzyme inhibition with captopril 25 mg. A captopril-mediated decrease in mean arterial pressure was predicted by 3 factors (r2 = 0.74): the decrease in serum angiotensin II (F ratio = 10.3, p < 0.01), the decrease in plasma norepinephrine (F = 8, p = 0.02), and, inversely by pretreatment mean arterial pressure (F = 5.6, p = 0.04), patients with higher initial values exhibiting greater decreases in response to captopril. A captopril-mediated decline in glomerular filtration rate, determined by radioisotope elimination, was also predicted by 3 factors (r2 = 0.67): a decrease in renal plasma flow (F = 48.6, p < 0.01), low pretreatment glomerular filtration rate (F = 11.1, p < 0.01), and low absolute post-treatment serum angiotensin II (F = 5, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
Motwani
J G
JG
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland.
Fenwick
M K
MK
Morton
J J
JJ
Struthers
A D
AD
D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000008:administration & dosage / Q000627:therapeutic use*; D003327:Coronary Disease / Q000150:complications*; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D009638:Norepinephrine / Q000097:blood; D010919:Placebos; D017595:Renal Plasma Flow / Q000187:drug effects; D012964:Sodium / Q000652:urine
D010919:Placebos; D000804:Angiotensin II; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D002216:Captopril; D012964:Sodium; D009638:Norepinephrine