Haemodynamic (systemic and renal) and humoral interactions between nicardipine and domperidone in hypertensives.
We studied the haemodynamic (systemic and renal) and humoral effects of nicardipine, a dihydropyridine calcium entry blocker in essential hypertensives and whether DA2 dopaminergic receptor blockade, induced by domperidone, might modify these effects. Eight uncomplicated mild to moderate hypertensives received placebo (saline) for 30 min followed by i.v. nicardipine (0.06 mg/min) for 30 min and repeated the same sequence introducing domperidone (10 mg i.v.) between saline and nicardipine; the effects of each treatment were followed for 30 min. The sequence was randomized with a 72-h interval between each study. Compared with placebo, nicardipine significantly reduced mean blood pressure (-14%) and renovascular resistance (-28%), increased heart rate (+15%), renal plasma flow (RPF; +21%), glomerular filtration rate (GFR; +43%) and urinary sodium excretion (+181%). The acute natriuretic effect of nicardipine was associated with an increase in the amount of filtered sodium (+43%) and with fractional sodium excretion (+110%), and a direct correlation was found between changes in RPF and in urinary sodium excretion (r = 0.68) and fractional sodium excretion (r = 0.57). Plasma renin activity (PRA) did not change, plasma aldosterone was significantly reduced (-10%) and plasma noradrenaline significantly increased (+63%). Domperidone pretreatment prevented the GFR increase induced by nicardipine and increased the noradrenaline response (+107%), but did not change the other actions of nicardipine. These data show that nicardipine, when acutely infused in essential hypertensives, while reducing blood pressure and reflexly activating the sympathetic nervous system, significantly increases urinary sodium excretion, RPF and GFR.(ABSTRACT TRUNCATED AT 250 WORDS)
Lucarini
A R
AR
Clinica Medica I, University of Pisa, Italy.
Salvetti
A
A
D000328:Adult; D000450:Aldosterone / Q000097:blood; D004294:Domperidone / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D011897:Random Allocation; D012083:Renin / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects
D000450:Aldosterone; D004294:Domperidone; D009529:Nicardipine; D012083:Renin; D009638:Norepinephrine