Ss. Sorensen et al., EFFECT OF ISRADIPINE ON RENAL HEMODYNAMICS AND SYSTEMIC BLOOD-PRESSURE CHANGES INDUCED BY INTRAVENOUS-INFUSION OF ENDOTHELIN IN HEALTHY HUMANS, Nephrology, dialysis, transplantation, 10(8), 1995, pp. 1324-1331
Background. In some vascular beds calcium-channel-blocking agents have
been shown to posses some antagonism to endothelin-1 (ET-1)-induced v
asoconstriction. This issue has not been well investigated in humans,
however. Methods. The study had a double-blind cross-over design. In 1
2 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 sodiu
m and water induced by intravenous infusion of ET-1 at a rate of 1 pmo
l/min/kg for 60 min. Results. Infusion of ET-1 affected systemic haemo
dynamics. The increase in diastolic blood pressure was similar after p
retreatment 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 r
ate (-8.8% versus -10.9%) and renal vascular resistance (+55.1% versus
+52.7%). Likewise the changes in renal handling of sodium and water i
n response to ET-1 infusion were unaffected by pretreatment with place
bo 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% vers
us -29.1%). Conclusions. Intravenous infusion of ET-1 in healthy human
s discretely increases diastolic blood pressure and profoundly decreas
es renal haemodynamics and excretion of sodium and water. Pretreatment
with the calcium-channel blocking agent isradipine for 1 week in a cl
inically relevant dose does not interfere with the action of ET-1.