Physiologists are studying the forces governing glomerular ultrafiltration using a single nephron in an intact kidney of an experimental animal. Hydrostatic pressure in the glomerular capillary and Bowman space is measured using micropipette transducers. Colloid osmotic pressure in the glomerular capillary is estimated using the difference in plasma protein concentration in the afferent and efferent arterioles. The glomerular surface is assumed to be functionally intact with negligible filtration of plasma proteins into the Bowman space. From the data obtained, net filtration pressure is calculated at 10 mm Hg. A substance is instilled into the renal artery, and measurements are repeated. The net filtration pressure after the intervention is 20 mm Hg. Which of the following substances was most likely used in this experiment?
Show Explanatory Sources
The net filtration pressure is a result of pressure gradients formed by Starling forces and is calculated by subtracting the oncotic pressure gradient from the hydrostatic pressure gradient (ie, net filtration pressure = [Pc − Pi] − [πc − πi]):
The hydrostatic pressure gradient (Pc − Pi) is the difference between the hydrostatic pressure in the intraglomerular capillaries and Bowman's space. Hydrostatic pressure in the capillaries is higher than in Bowman's space, and provides the driving force for fluid efflux from the capillaries.
The oncotic pressure gradient (πc − πi) is the difference between the oncotic pressure in the intraglomerular capillaries and Bowman's space. Oncotic pressure is driven chiefly by large plasma proteins (eg, albumin), which do not freely filter across the glomerular capillary basement membrane due to both a size and a charge barrier. The high oncotic pressure in the capillaries counteracts the capillary hydrostatic pressure and decreases net fluid efflux from the capillaries.
This patient's net filtration pressure has increased from 10 to 20 mm Hg after infusion of a substance. Increased net filtration pressure occurs due to either an increase in the hydrostatic pressure gradient or a decrease in the oncotic pressure gradient. Of the available options, only an angiotensin II agonist would increase the net filtration pressure. Angiotensin II preferentially constricts the efferent arteriole, resulting in an increased hydrostatic pressure gradient and increased net filtration pressure.
(Choice A) Albumin is not filtered across the glomerular capillary and would increase the oncotic pressure gradient, resulting in a lower net filtration pressure.
(Choice B) Alpha-1 receptors are located mainly in the afferent arteriole; alpha agonists (eg, epinephrine, norepinephrine) result in constriction of the afferent arteriole, which reduces hydrostatic pressure and leads to lower net filtration pressures.
(Choice D) Prostaglandins (eg, prostaglandin E2) are responsible for dilation of the afferent arteriole. Inhibition of prostaglandin synthesis, as seen with nonsteroidal anti-inflammatory drugs, results in constriction of the afferent arteriole, leading to reduced hydrostatic pressure and a lower net filtration pressure.
(Choice E) Vasopressin 2 antagonists (eg, tolvaptan) reduce vasopressin-induced free water resorption. These drugs do not have a direct effect on the Starling forces; however, reduced free water resorption can result in decreased blood volume, which decreases capillary hydrostatic pressure, which would lower the net filtration pressure.
Educational objective:
The net filtration pressure is a result of pressure gradients formed by Starling forces and is calculated by subtracting the oncotic pressure gradient from the hydrostatic pressure gradient. Angiotensin II preferentially constricts the efferent arteriole, resulting in an increased hydrostatic pressure gradient and an increased net filtration pressure.