Modulation by prostaglandin synthesis inhibitors of the action of exogenous angiotensin II on glomerular ultrafiltration in the rat.
We studied the effects of angiotensin II (A II) infusion, with and without inhibition of prostaglandin (PG) synthesis, on the determinants of glomerular ultrafiltration in 27 plasma volume-expanded Munich-Wistar rats. The effects of PG inhibition alone and infusion of vehicle alone also were investigated. With a pressor dose of A II single nephron (SN) GFR and total GFR did not change significantly, despite declines in both glomerular plasma flow rate (QA) and the ultrafiltration coefficient (Kf), due to an offsetting rise in the transcapillary hydraulic pressure difference (deltaP). Afferent and efferent arteriolar resistances (RA and RE) increased by approximately 100% above control during A II infusion. Inhibition of PG synthesis alone and infusion of vehicle alone similarly failed to affect SNGFR and total GFR, and only slight changes occurred in the determinants of glomerular ultrafiltration in these rats. When A II infusion was accompanied by inhibition of PG synthesis, however, profound declines in SNGFR and total GFR were seen, due to further reductions in QA and 2-fold greater increases in RA and RE than occurred with the same dose of A II alone. The A II-induced fall in Kf was not affected by simultaneous PG inhibition. Thus, endogenous PGs attenuate the vasoconstrictor actions of A II on the superficial renal microvasculature and minimize changes in QA, SNGFR, and total GFR. It is likely that an interaction between A II and PG may be important in pathophysiological conditions in which endogenous A II levels are elevated.
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins; D002196:Capillaries / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects*; D007687:Kidney Tubules, Proximal / Q000187:drug effects; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009399:Nephrons / Q000187:drug effects; D009997:Osmotic Pressure; D010953:Plasma Volume; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D001798:Blood Proteins; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D000804:Angiotensin II; D008469:Meclofenamic Acid; D007213:Indomethacin