Carin Larsson

Arachidonic acid increases and indomethacin decreases plasma renin activity in the rabbit

Abstract Plasma renin activity (PRA) was measured in rabbits before and after infusion of the prostaglandin precursor, arachidonic acid (C20:4) and of the prostaglandin synthesis inhibitor, indomethacin. Non-hypotensive doses of C20:4 (10–15 μg/kg/min) increased PRA from 45 ± 7.3 to 91 ± 16 ng/ml/hr ( n = 6, p n = 4, p

Regional differences in the formation and metabolism of prostaglandins in the rabbit kidney

Abstract The biosynthesis and metabolism of prostaglandins was studied in three microscopically defined regions of rabbit kidney, the cortex, the outer and the inner medulla. PGE 2 formation was highest in the inner medulla, but significant biosynthesis occured also in the cortex. Metabolism of prostaglandins by 15-hydroxyprostaglandin dehydrogenase occured predominantly in the cortex with levels 10 times those seen in the inner medulla. The results thus demonstrate a clearcut dissociation between the sites of biosynthesis and metabolism in the kidney. The function of the cortical PGDH might be either to inactive prostaglandins formed in medulla or to protect medullary PG receptors from high levels of circulating prostaglandins.

Prostaglandin E2-9-ketoreductase as a mediator of salt intake-related prostaglandin-renin interaction

PREVIOUS studies have revealed a close relationship between the prostaglandin (PG) and the renin–angiotensin systems in the kidney1–4 and we assume that both systems are intimately involved in the regulation of salt and volume homeostasis and of blood pressure. Changes in NaCl and water balance were found to be important determinants of the activity and function of the renin–angiotensin system5 and it has been suggested that PG synthesis is also modified by these variables2,6,7. One factor influencing the pathway and, thus, the consequences of altered PG formation is the enzyme PGE2-9-ketoreductase, which catalyses the interconversion of the antagonistically acting PGE2 and PGF2α (ref. 8). First direct evidence is presented here that PGE2-9-ketoreductase activity is under the control of NaCl ingestion. We suggest that this enzyme is an important mediator of salt intake-related prostaglandin–renin interaction.

Increase of free arachidonic acid by furosemide in man as the cause of prostaglandin and renin release

Arachidonic acid (C20 :4) plasma renin activity (PRA), PGF2alpha, and sodium excretion were determined before and after furosemide in men. C20 : 4 and PRA increase (p less than 0.005) within 10 min after furosemide, PRA then decreased again whereas C20 : 4 levels remained elevated. Maximal exretion of PGF2alpha and sodium occurred 30-60 min after furosemide. Indomethacin prevented the rise of C20 : 4, PRA and PGF2alpha after furosemide, leaving sodium excretion unaltered. The release of C20 : 4 is assumed to be the primary mechanism of furosemide to increase PG biosynthesis and renin release.

The sequence of the early steps in the metabolism of prostaglandin E1.

Abstract The pathway in the metabolism of prostaglandins E 1 in kidney, spleen and liver from swine is 1) oxidation of the 15-hydroxyl group to a ketone, 2) reduction of the Δ 13 -double bond and partly 3) stereospecific reduction of the 15-keto group to dihydro-prostaglandin E 1 (15 S).

Increased juxtamedullary blood flow on stimulation of intrarenal prostaglandin biosynthesis.

Abstract Regional blood flow distribution in the rabbit kidney was studied with radioactive microspheres before and during infusion of sodium arachidonate (C20:4). C20:4 (15–25 μg/kg/min) increased the ratio of juxtamedullary to superficial cortical blood flow by 12 ± 2.3% (n = 7) and caused an increase of 50 ± 15% (n = 5) in the output of urinary prostaglandins, mainly prostaglandin E2. Indomethacin (10–20 mg/kg) given before the C20:4 infusion (n = 4) decreased the ratio of juxtamedullary to superficial cortical blood flow by 22 ± 7% and decreased the output of urinary prostaglandins. The results provide evidence for a role of prostaglandin E2 as an intrarenal hormone regulating the inner cortical and medullary circulation of blood flow.

Reduction by indomethacin of furosemide effects in the rabbit

The effects of furosemide on urine flow, sodium and potassium excretion and on plasma renin activity (PRA) were studied in anesthetized rabbits with and without pretreatment with indomethacin 5 mg/kg. Furosemide caused a 10-fold increase in urine flow and in sodium excretion, and a 2-3 fold increase in PRA. Pretreatment with the prostaglandin synthesis inhibitor, indomethacin, reduced the effects of furosemide on diuresis and on electrolyte excretion by over 80% (p less than 0.01) and PRA did not increase over the initial level. The results suggest that the effects of furosemide on PRA and on urinary sodium excretion may be related to the intrarenal activation of the prostaglandin system.

Indomethacin and diclofenac sodium increase sodium and water excretion after extracellular volume expansion in the rabbit

The renal effects of an acute extracellular fluid volume expansion (50 ml Ringer/kg body weight/60 min) were studied in aldosterone-treated (100 microgram/kg), anesthetized rabbits with and without pretreatment with either indomethacin (3.0 mg/kg) or diclofenac sodium (3.0 mg/kg), two different inhibitors of renal prostaglandin (PG) biosynthesis. In controls (n = 7), the volume expansion increased urine flow from 1.5 +/- 0.24 to 6.1 +/- 0.5 (S.E.) ml/min/100 g kidney weight and sodium excretion from 0.15 +/- 0.03 to 0.99 +/- 0.10 mmol/min/100 g. PAH and inulin clearance increased by 42 and 58%, respectively, while plasma renin activity and urinary excretion of PGF2 alpha-like immunoreactivity were reduced (P less than 0.05). In animals pretreated with indomethacin (n = 6) or diclofenac sodium (n = 6), the diuresis and the natriuresis following volume expansion were significantly increased about two-fold over controls, whereas PAH and inulin clearance, plasma renin activity and hematocrit did not differ from controls. Both drugs were found to reduce urinary excretion of PGF2 alpha-like immunoreactivity by 75--95% througout the experiment. The results indicate that diclofenac sodium, indomethacin and extracellular volume expansion enhance sodium and water excretion partly by suppression of a PG sensitive reabsorption process in the kidney.