Total and Intrarenal Flow Distribution in Healthy Subjects: Technique, Acute Effects of Ibopamine and of Indoramin

Abstract

A technique is described for measuring an index of cardiac output, total and individual renal plasma flow, cortical and juxtamedullary nephron flow non-invasively in man with a single injection of ¹²³I-o-iodohippurate. Ibopamine, a dopamine analogue, was administered orally, 200 and 600 mg, in a double-blind, placebo-controlled cross-over study in 6 healthy subjects. No change in pulse, blood pressure, cardiac output, urea, creatinine or electrolytes was seen. Ibopamine reduced effective renal plasma flow and cortical nephron flow and increased urine flow significantly. This may be due to differential vasoconstrictor and vasodilator effects on the two populations of nephrons. Indoramin, an alpha-1 postsynaptic adrenoceptor blocker, was administered orally, 50 mg, in a double-blind, placebo-controlled cross-over study in 14 healthy young males. No change in pulse, cardiac output, urea, creatinine or electrolytes was seen. Indoramin significantly reduced upright but not supine blood pressure and significantly increased effective renal plasma flow. Cortical nephron flow and juxtamedullary nephron flow tended to rise. Plasma renin activity was significantly elevated althouth there was no change in urinary sodium output. The effect of drugs on intrarenal blood flow distribution may be relevant to the management of essential hypertension.

Renal and neurohumoral effects of ibopamine and metoclopramide in normal man.

“…In healthy volunteers renal haemodynamic effects of ibopamine have been assessed only by calculation of endogenous creatinine clearances (Harvey et al, 1984;Incerti et al, 1986;Stefoni et al, 1981), with the exception of a small study by Britton who measured ERPF (Britton et al, 1986). A pronounced increase in creatinine clearance with a dose of 50 mg was found in an acute open study by Incerti et al (1986).…”

Ibopamine - How Should It Be Used?

“…The authors treated volunteers with doses ranging between 100 and 600 mg. Cicchetti et al [50], Melloni et al [35] and Britton et al [51], on the con trary, found a 20% (50-200 mg) and 60% (600 mg) increase in diuresis, respectively, also with double-blind experimental proto cols. During 5-day treatment with 50 mg ibo pamine b.i.d., a progressive increase in di uresis and sodium and potassium excretion in urine, and an increase in creatinine clear ance were observed.…”

The Effect of Ramipril. A New Angiotensin-Converting Enzyme Inhibitor on Cortical Nephron Flow and Effective Renal Plasma Flow in Patients with Essential Hypertension

“…Cl is obtained by dividing the equilibrium value by the area under the first pass curve corrected for recirculation using an exponential extrapolation from the maxi mum gradient of the downstroke to define its limits. A normal Cl lies between 0.75 and 1.25 blood vol/min [10],…”

“…The technique has been validated against microsphere distribu tion in the rabbit and pig [6], by sensitivity analysis whereby it was shown that a l-min difference in transit time between the cortical and juxtamedullary transit times was necessary to be 95% certain in separating the two components [18] and by showing that the inde pendent calculated difference in CN flow of the two kidneys in a patient was within 3% [7], Studies in normal volunteers have been published in this journal [10].…”

“…The hippuran (OIH) transit time method for measur ing IRPF distribution has been validated in animal experiments and in man [4][5][6] and various applications have proved its value in calculating the differential plasma flow to cortical and juxtamedullary nephrons (JMN) in volunteers and in patients with essential hyper tension [7][8][9][10].…”