Comparison of dopamine and fenoldopam effects on renal blood flow and prostacyclin excretion in normal and essential hypertensive subjects.
We recently reported that a low dose dopamine (DA) infusion in normal subjects increased renal blood flow (RBF) via prostacyclin (PGI2) formation without changes in PGE2 levels. The present study explores whether this mechanism is mediated by the DA1 receptor and evaluates the effect of DA on RBF and PGs in subjects with essential hypertension (EH). A low dose of DA (1 microgram/kg.min), which previously did not alter hemodynamics in normal subjects was infused into eight patient with EH to determine the role of DA stimulation in hypertensives. To assess the effect of DA1 stimulation, fenoldopam, a selective DA1 agonist, was infused (0.1 microgram/kg.min) into 10 normal and 10 hypertensive patients. Fenoldopam, unlike DA, significantly decreased diastolic blood pressure in hypertensives (96 +/- 3 to 85 +/- 2 mm Hg; P less than 0.01) along with a significant increase in pulse rate (68 +/- 2 vs. 73 +/- 2 beats/min; P less than 0.01). RBF measured by para-aminohippurate clearance increased only in normals during fenoldopam infusion from 1185 +/- 71 to 1533 +/- 84 L/min.m2 (PGI(2)01), and this was associated with an increase in PGI2 (6-keto-PGF1) excretion (149 +/- 19 vs. 214 +/- 32 ng/g creatinine; P less than 0.02). These effects of fenoldopam were similar to DA effects on RBF and PGI2 excretion in normals. In contrast, in hypertensive subjects, neither fenoldopam (867 +/- 113 vs. 1054 +/- 177 L/min.m2; P greater than 0.1) nor DA (1098 +/- 85 vs. 1061 +/- 101 L/min.m2; P greater than 0.1) increased RBF. Similarly, neither the DA nor the fenoldopam infusion stimulated PGI2 excretion in the hypertensives. The fenoldopam infusion in the hypertensives produced a significant natriuresis (22 +/- 3 to 49 +/- 9 mmol/3 h; P less than 0.05). Similar effects on Na+ excretion in this group were noted during DA infusion (17 +/- 3 to 36 +/- 3 mmol/3 h; P less than 0.05), suggesting that DA-induced natriuresis is not directly linked to DA-induced changes in RBF or PG excretion. The present study shows that in normal subjects, fenoldopam, a specific DA1 agonist, like DA, stimulates renal PGI2 release and RBF. In contrast, neither DA nor fenoldopam alters PGI2 or RBF in patients with EH, suggesting an alteration of dopaminergic tone in some hypertensives that is characterized by a defect in DA1 receptor sensitivity.
Bughi
S
S
Section of Endocrinology, University of Southern California School of Medicine, Los Angeles 90033.
Horton
R
R
Antonipillai
I
I
Manoogian
C
C
Ehrlich
L
L
Nadler
J
J
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D011464:Epoprostenol / Q000652:urine*; D018818:Fenoldopam; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000652:urine; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine
D015259:Dopamine Agents; D000450:Aldosterone; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D012964:Sodium; D011464:Epoprostenol; D012083:Renin; D018818:Fenoldopam; D011188:Potassium; D004298:Dopamine