Renal effects of fenoldopam in refractory hypertension

Renal and hemodynamic effects of intravenous fenoldopam versus nitroprusside in severe hypertension.

“…This study confirms and extends previous studies that have demonstrated the antihypertensive efficacy of fenoldopam, both after oral'8-21 and, especially, intravenous1314, 17,19,[22][23][24][25] have shown that intravenous fenoldopam is effective in mild-to-moderate hypertension,14 refractory hypertension (i.e., patients with diastolic blood pressures >115 mm Hg on triple-drug therapy),23 and severe hypertension,172425 but this is the first series to include a majority of patients with accelerated/ malignant hypertension, which is presumably the population in which it will find the widest use. In addition, the present series includes a preponderance of black patients, who comprise a small minority of those previously treated with fenoldopam.17 Indeed, because of the greater frequency of severe hypertension and its complications (including accelerated/malignant hypertension) in blacks,26'27 fenoldopam may be especially useful in such patients, who more commonly have reduced salt and water excretion rates,28 independent of the degree of renal dysfunction.…”

Dopamine D1 receptor (DRD1) genetic polymorphism: pleiotropic effects on heritable renal traits

“…Thus, coordinate actions of the A/A diploid genotype to lower both GFR and albuminuria suggest diminished glomerular capillary hydrostatic pressure as a potential mechanism. We also found effects of the genetic variant on renal uric acid transport traits (Table 2, Figure 2c), suggesting that D 1 receptors may influence other aspects of renal function, as has been previously suggested 10,11. In addition, we carried out assays with plasmid constructs of WT and variant DRD1 genes transfected into heterologous cells and found that the -94A variant, but not the -48G variant, had increased maximal binding capacity.…”

The role of DA1‐ and DA2‐receptors in the control of blood pressure.

“…Several clinical studies with fenoldopam in hypertensive patients show the drug to produce an immediate reduction in systolic and diastolic blood pressure Ruilope et al, 1988;White et al, 1988). No tachyphylaxis is observed, even when the drug infusion is maintained for up to 24 h. The magnitude of the antihypertensive effect of intravenous fenoldopam is proportional to the pre-infusion pressure, with the drug being capable of producing blood pressure reductions of over 40 mm Hg in severely hypertensive patients (Figure 1).…”

“…This would suggest that under these conditions there is no evidence for downregulation of the DA1-receptor(s) responsible for the control of blood pressure, although the interpretation of the oral studies is complicated, since continuous DA1-receptor activation was not produced by the dosing regimen utilized. (Ruilope et al, 1988) and 0.1 to 0.4 ,ug (mean 0.34) (White et al, 1988 (Hahn, 1989;Hieble et al, 1987, 198 (Costall et al, 1988 Quinpirole, generally regarded as a highly selective DA2-receptor agonist, has been extensively studied as an antihypertensive drug in animal models (Hahn, 1989). However, in conscious rats, quinpirole can increase blood pressure.…”

“…Under the proper conditions dopamine can produce a dramatic reduction in blood pressure in hypertensive patients , and several dopamine receptor agonists have been shown to be effective antihypertensive drugs, either for acute administration in hypertensive crisis (Guffanti et al, 1985;Ruilope et al, 1988;White et al, 1988) or for chronic oral therapy (Lombardi et al, 1987;Mercuro et al, 1986).…”