Effect of isradipine on renal haemodynamics and systemic blood pressure changes induced by intravenous infusion of endothelin in healthy humans.
BACKGROUND
In some vascular beds calcium-channel-blocking agents have been shown to possess some antagonism to endothelin-1 (ET-1)-induced vasoconstriction. This issue has not been well investigated in humans, however.


METHODS
The study had a double-blind cross-over design. In 12 healthy human volunteers we investigated the effect of pretreatment with either isradipine 10 mg daily for 1 week or placebo on changes in (i) systemic and renal haemodynamics and (ii) renal handling of sodium and water induced by intravenous infusion of ET-1 at a rate of 1 pmol/min/kg for 60 min.


RESULTS
Infusion of ET-1 affected systemic haemodynamics. The increase in diastolic blood pressure was similar after pretreatment with placebo (+6.8%) or isradipine (+5.3%). The changes in renal haemodynamics in response to ET-1 infusion were also familiar, e.g. renal plasma flow (-32.1% versus -31.2%), glomerular filtration rate (-8.8% versus -10.9%) and renal vascular resistance (+55.1% versus +52.7%). Likewise the changes in renal handling of sodium and water in response to ET-1 infusion were unaffected by pretreatment with placebo or isradipine, e.g. sodium excretion (-44.6% versus -40.8%), urine flow rate (-49.8% versus -38.9%) and clearance of lithium (-32.0% versus -29.1%).


CONCLUSIONS
Intravenous infusion of ET-1 in healthy humans discretely increases diastolic blood pressure and profoundly decreases renal haemodynamics and excretion of sodium and water. Pretreatment with the calcium-channel blocking agent isradipine for 1 week in a clinically relevant dose does not interfere with the action of ET-1.
Sørensen
S S
SS
Department of Nephrology and Medicine C, Skejby Hospital, University Hospital in Aarhus, Denmark.
Jensen
J D
JD
Madsen
J K
JK
Pedersen
E B
EB
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D016232:Endothelins / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D017275:Isradipine / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D012016:Reference Values; D017595:Renal Plasma Flow / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism; D014867:Water / Q000378:metabolism
D002121:Calcium Channel Blockers; D016232:Endothelins; D014867:Water; D012964:Sodium; D017275:Isradipine