Papillary collecting tubule synthesis of prostaglandin E2 in Dahl rats.
Isolated kidneys of Dahl salt-sensitive rats (DS) excrete sodium less readily than those of Dahl salt-resistant rats (DR). The collecting tubule is an important source of papillary prostaglandin E2 and is a site of significant sodium reabsorption. We cultured renal papillary collecting tubule cells from 5-week-old, prehypertensive DS and DR on a low salt diet and also after 14 weeks of high salt feeding, and we measured prostaglandin E2 synthetic capacity. Unstimulated renal papillary collecting tubule cells from 5-week-old DS produced 62 +/- 5% less prostaglandin E2 than did comparable cells from DR (p less than 0.001). The cells from DS also synthesized less prostaglandin E2 after stimulation with the calcium ionophore A23187 (67 +/- 6% of control; p less than 0.001) or the addition of exogenous arachidonate (74 +/- 7% of control; p less than 0.01). Urinary prostaglandin E2 excretion was also diminished in the 5-week-old DS compared with their salt-resistant counterparts (18.1 +/- 1.3 vs 23.9 +/- 1.7 ng/24 hr; p less than 0.025). After high salt feeding, the DS became hypertensive but the DR remained normotensive. Renal papillary collecting tubule cells cultured from these DS continued to produce less prostaglandin E2 than those from control rats, both in the basal state (60 +/- 12% of control; p less than 0.09) and after stimulation with ionophore (62 +/- 2% of control; p less than 0.002). In these older animals, the DS continued to underexcrete prostaglandin E2 compared with the DR (29.7 +/- 3.2 vs 42.2 +/- 6.1 ng/24 hr; p less than 0.08). The underproduction of prostaglandin E2 in the papillary collecting tubule of DS may play a role in their inadequate renal natriuretic capacity and contribute to the onset and maintenance of salt-induced hypertension in this strain.
Department of Medicine, Case Western Reserve University, Cleveland, Ohio.
G M
GM
Reid
R G
RG
Appel
M J
MJ
Dunn
D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D009318:Natriuresis; D011458:Prostaglandins E / Q000096:biosynthesis*; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011919:Rats, Inbred Strains / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D012965:Sodium Chloride / Q000008:administration & dosage
D011458:Prostaglandins E; D012965:Sodium Chloride; D012964:Sodium; D015232:Dinoprostone