Hemodynamic, renal, and neurohumoral effects of a selective oral DA1 receptor agonist (fenoldopam) in patients with congestive heart failure.
Fenoldopam mesylate (SK&F 82526-J) is a novel benzazepine derivative. It has selective agonist activity at post-junctional (DA1) vascular dopaminergic receptors, which normally subserve renal artery vasodilation. Previous studies in normal subjects and in patients with hypertension indicate that fenoldopam increases renal blood flow and promotes a sodium diuresis. Drug efficacy was clinically evaluated in eight patients with chronic congestive heart failure (CHF) after a single oral dose of 100 mg of fenoldopam and following 3 days of therapy (100 mg four times daily). Stroke volume index acutely increased from 26 +/- 7 (mean +/- SD) to 30 +/- 4 ml/beat/m2 (p less than 0.05) and left ventricular filling pressure decreased from 26 +/- 13 to 23 +/- 11 mm Hg (p less than 0.05). Systemic vascular resistance decreased from 1513 +/- 159 to 1128 +/- 319 (p less than 0.05). Hemodynamic changes were seen as early as 30 minutes following fenoldopam and returned to control levels by 4 hours. Forearm blood flow, hepatic blood flow, and venous capacitance did not significantly change acutely, but renal blood flow index was significantly reduced (34 +/- 4 to 30 +/- 3 min-1 X 1000, p less than 0.01). Plasma norepinephrine, plasma renin activity, plasma arginine vasopressin, and plasma aldosterone did not significantly change acutely. After 3 days of treatment, 100 mg of fenoldopam again reduced the renal blood flow index (35 +/- 7 to 26 +/- 7 min-1 X 1000, p less than 0.01) and tended to increase plasma renin activity (11.7 +/- 8 to 21.2 +/- 19.4 ng/ml/hr, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
D000284:Administration, Oral; D000450:Aldosterone / Q000378:metabolism; D001127:Arginine Vasopressin / Q000378:metabolism; D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018818:Fenoldopam; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D012039:Regional Blood Flow; D012083:Renin / Q000378:metabolism; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D001552:Benzazepines; D011954:Receptors, Dopamine; D014665:Vasodilator Agents; D001127:Arginine Vasopressin; D000450:Aldosterone; D012083:Renin; D018818:Fenoldopam; D009638:Norepinephrine