Richard J. Solomon

Effects of Saline, Mannitol, and Furosemide on Acute Decreases in Renal Function Induced by Radiocontrast Agents

BACKGROUND Injections of radiocontrast agents are a frequent cause of acute decreases in renal function, occurring most often in patients with chronic renal insufficiency and diabetes mellitus. METHODS We prospectively studied 78 patients with chronic renal insufficiency (mean [+/- SD] serum creatinine concentration, 2.1 +/- 0.6 mg per deciliter [186 +/- 53 mumol per liter]) who underwent cardiac angiography. The patients were randomly assigned to receive 0.45 percent saline alone for 12 hours before and 12 hours after angiography, saline plus mannitol, or saline plus furosemide. The mannitol and furosemide were given just before angiography. Serum creatinine was measured before and for 48 hours after angiography, and urine was collected for 24 hours after angiography. An acute radiocontrast-induced decrease in renal function was defined as an increase in the base-line serum creatinine concentration of at least 0.5 mg per deciliter (44 mumol per liter) within 48 hours after the injection of radiocontrast agents. RESULTS Twenty of the 78 patients (26 percent) had an increase in the serum creatinine concentration of at least 0.5 mg per deciliter after angiography. Among the 28 patients in the saline group, 3 (11 percent) had such an increase in serum creatinine, as compared with 7 of 25 in the mannitol group (28 percent) and 10 of 25 in the furosemide group (40 percent) (P = 0.05). The mean increase in serum creatinine 48 hours after angiography was significantly greater in the furosemide group (P = 0.01) than in the saline group. CONCLUSIONS In patients with chronic renal insufficiency who are undergoing cardiac angiography, hydration with 0.45 percent saline provides better protection against acute decreases in renal function induced by radiocontrast agents than does hydration with 0.45 percent saline plus mannitol or furosemide.

Oxygen cost of chloride transport in perfused rectal gland ofSqualus acanthias

SummaryIn the stimulated state, with glucose as substrate, oxygen uptake by the isolated perfused rectal gland is directly related to the rate of chloride secretion. Lactate production is negligible under aerobic conditions in the stimulated gland. A stoichiometric relationship exists between chloride transport and oxygen consumption, with a Cl/O2 ratio of about 30∶1, resembling that reported for sodium in mammalian kidneys. This ratio remains constant under varying degrees and modes of stimulation. The ratio does not change when the gland is induced to secrete chloride against varying electrochemical gradients by altering the concentration of urea in the perfusate.

Mode of activation of salt secretion by C-type natriuretic peptide in the shark rectal gland

We studied the modes of activation of the salt-secreting rectal gland of the spiny dogfish, Squalus acanthias, by the native cardiac peptide CNP. The stimulatory action of CNP in isolated perfused glands is inhibited by 10 mM procaine, presumably by blocking release of vasoactive intestinal peptide (VIP) from nerves. Procaine reduces the slope of the dose-response curve of human CNP and that of shark CNP (each P < 0.0001). CNP increases short-circuit current in cultured rectal gland cells from 4.8 +/- 1.6 to 27.0 +/- 7.8 microA/cm2. It also stimulates the secretion of chloride in isolated perfused glands in the presence of 10 mM procaine from 72 +/- 31 to 652 +/- 173 microeq. h(-1). g(-1). These results suggest that CNP has a direct cellular action not mediated by the neural release of VIP. The residual stimulation of perfused glands in the presence of procaine was almost completely inhibited by staurosporine [10 nM; an inhibitor of protein kinase C (PKC)] from 652 +/- 173 to 237 +/- 61 microeq. h(-1). g(-1). Although CNP stimulates guanylyl cyclase in shark rectal gland, chloride secretion of perfused glands was not elicited by 8-bromoadenosine-cGMP (8-BrcGMP) alone nor by the activator of PKC phorbol ester. The combination of PKC activation and 8-BrcGMP infusion, however, stimulated chloride secretion in perfused glands from 94 +/- 30 to 506 +/- 61 microeq. h(-1). g(-1), a level comparable to that observed in glands blocked with procaine. Several parallel pathways appear to be synergistic in activating chloride secretion stimulated by CNP in the rectal gland.We studied the modes of activation of the salt-secreting rectal gland of the spiny dogfish, Squalus acanthias, by the native cardiac peptide CNP. The stimulatory action of CNP in isolated perfused glands is inhibited by 10 mM procaine, presumably by blocking release of vasoactive intestinal peptide (VIP) from nerves. Procaine reduces the slope of the dose-response curve of human CNP and that of shark CNP (each P < 0.0001). CNP increases short-circuit current in cultured rectal gland cells from 4.8 ± 1.6 to 27.0 ± 7.8 μA/cm2. It also stimulates the secretion of chloride in isolated perfused glands in the presence of 10 mM procaine from 72 ± 31 to 652 ± 173 μeq ⋅ h-1 ⋅ g-1. These results suggest that CNP has a direct cellular action not mediated by the neural release of VIP. The residual stimulation of perfused glands in the presence of procaine was almost completely inhibited by staurosporine [10 nM; an inhibitor of protein kinase C (PKC)] from 652 ± 173 to 237 ± 61 μeq ⋅ h-1 ⋅ g-1. Although CNP stimulates guanylyl cyclase in shark rectal gland, chloride secretion of perfused glands was not elicited by 8-bromoadenosine-cGMP (8-BrcGMP) alone nor by the activator of PKC phorbol ester. The combination of PKC activation and 8-BrcGMP infusion, however, stimulated chloride secretion in perfused glands from 94 ± 30 to 506 ± 61 μeq ⋅ h-1 ⋅ g-1, a level comparable to that observed in glands blocked with procaine. Several parallel pathways appear to be synergistic in activating chloride secretion stimulated by CNP in the rectal gland.

Role of guanylyl cyclase receptors for CNP in salt secretion by shark rectal gland

The role of C-type natriuretic peptide (CNP) and its guanylyl cyclase-linked receptors in mediating salt secretion by the rectal gland of the spiny dogfish shark ( Squalus acanthias) was investigated using HS-142-1, a competitive inhibitor of the binding of natriuretic peptides to their guanylyl cyclase receptors. CNP binds to receptors and activates guanylyl cyclase in rectal gland membranes in a way that is inhibited by HS-142-1. Guanylyl cyclase activation in rectal gland membranes is far more sensitive to CNP than to atrial natriuretic peptide, whereas the reverse is true for membranes derived from mammalian (rabbit) renal collecting duct cells. HS-142-1 inhibited the stimulatory effect of CNP on ouabain-inhibitable oxygen consumption by rectal gland tubules. In explanted rectal glands continuously perfused with blood from intact donor sharks, HS-142-1 inhibited the increase in salt secretion normally provoked by infusing isotonic saline solutions into the donor animal. These results strongly support the view that CNP released into the systemic circulation in response to volume expansion mediates the secretion of chloride by the rectal gland via receptors linked to guanylyl cyclase.The role of C-type natriuretic peptide (CNP) and its guanylyl cyclase-linked receptors in mediating salt secretion by the rectal gland of the spiny dogfish shark (Squalus acanthias) was investigated using HS-142-1, a competitive inhibitor of the binding of natriuretic peptides to their guanylyl cyclase receptors. CNP binds to receptors and activates guanylyl cyclase in rectal gland membranes in a way that is inhibited by HS-142-1. Guanylyl cyclase activation in rectal gland membranes is far more sensitive to CNP than to atrial natriuretic peptide, whereas the reverse is true for membranes derived from mammalian (rabbit) renal collecting duct cells. HS-142-1 inhibited the stimulatory effect of CNP on ouabain-inhibitable oxygen consumption by rectal gland tubules. In explanted rectal glands continuously perfused with blood from intact donor sharks, HS-142-1 inhibited the increase in salt secretion normally provoked by infusing isotonic saline solutions into the donor animal. These results strongly support the view that CNP released into the systemic circulation in response to volume expansion mediates the secretion of chloride by the rectal gland via receptors linked to guanylyl cyclase.

Chloride transport and its inhibition by thiocyanate in gills of seawater teleosts.

Abstract 1. Intraperitoneal injections of sodium thiocyanate (0·14 to 0·20 mM per 100 g body wt) reduced chloride efflux across the gill by about 50% in seawater specimens of Anguilla rostrata and Pseudopleuronectes americanus. In Fundulus heteroclitus adapted to seawater, however, no inhibitory effect of thiocyanate could be detected. 2. Neither sodium perchlorate nor sodium iodide inhibited chloride efflux in Anguilla rostrata. Phloretin injected intravenously in Pseudopleuronectes americanus was likewise without effect on chloride flux. 3. Tracer quantities of 35SCN are accumulated against an electrochemical gradient by freshwater Anguilla rostrata and extruded against an electrochemical gradient by saltwater fish, suggesting that thiocyanate is transported by a mechanism similar or identical to that responsible for the active transport of chloride by teleost gills.

Aldosterone Effects on Renal Function in the Isolated Perfused Rat Kidney

The excretion of potassium and the reabsorption of sodium were studied in isolated perfused kidneys of adrenalectomized rats following the administration of aldosterone. Aldosterone (10-7&l