title: Acute and subacute prostaglandin and ANG II inhibition on glomerulotubular dynamics in rats.
abstract: Prostaglandins (PG) and angiotensin II (ANG II) contribute to regulation of glomerular microcirculation. Acute vs. chronic physiological alterations of glomerular hemodynamics that result from inhibition of either PG or ANG II, or both, and their interaction were examined. Four groups of Munich-Wistar rats were submitted to the following micropuncture studies in euvolemic conditions for measurements of glomerular hemodynamics and tubular fluid reabsorption: 1) an untreated control group, 2) 4- to 6-day inhibition of both PG and angiotensin-converting enzyme activity with meclofenamate and MK-421 (enalapril), 3) 4- to 6-day treatment with enalapril followed by acute PG inhibition in the second measurement period, 4) 4- to 6-day PG inhibition followed by acute enalapril treatment in the second period. Dual 4- to 6-day treatment decreased single-nephron filtration rate (SNGFR, 24 +/- 2 vs. 33 +/- 2 nl/min in control; P less than 0.05) as a result of decreases in single-nephron plasma flow (SNPF) and glomerular hydrostatic pressure gradient (delta P). Treatment with enalapril alone for 4-6 days did not reduce SNGFR and SNPF; however, delta P decreased. Acute addition of meclofenamate did not alter these factors. SNGFR was decreased with 4- to 6-day treatment of meclofenamate from 33 +/- 2 in control to 25 +/- 1 nl/min (P less than 0.05). Acute treatment with enalapril in the 4- to 6-day meclofenamate-treated rats increased SNGFR to values not different from control. The results demonstrated that glomerular hemodynamic alterations consequent to inhibition of ANG II and PG systems differ between chronic and acute treatments. Therefore, interpretation of the role of individual hormonal systems in the control of glomerular hemodynamics should be approached with caution, since effects may be altered by duration of treatment and involvement of other vasoactive systems.
authors.affiliation: Department of Medicine, University of California, San Diego School of Medicine, La Jolla 92093.
authors.forename: B J
authors.initials: BJ
authors.lastname: Tucker
authors.forename: R C
authors.initials: RC
authors.lastname: Blantz
mesh_terms: D000042:Absorption; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007678:Kidney Glomerulus / Q000098:blood supply*; D007684:Kidney Tubules / Q000098:blood supply*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008138:Loop of Henle / Q000378:metabolism; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009399:Nephrons / Q000502:physiology; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D011448:Prostaglandin Antagonists; D000804:Angiotensin II; D008469:Meclofenamic Acid; D004656:Enalapril