Arachidonate metabolites and the control of glomerular function.
The glomerulus is a dynamic structure capable of regulating the glomerular filtration rate (GFR) by mesangial contraction, thereby decreasing Kf. The mesangium contracts in response to angiotensin II (AII) and arginine vasopressin (AVP), both of which are potent stimuli of vasodilatory prostaglandin (PG) production. We studied interactions among these opposing factors in glomeruli. Normal rat glomeruli synthesized PGF2 alpha greater than PGE2 greater than 6-keto-PGF1 alpha = thromboxane (Tx) B2. Rat glomerular epithelial and mesangial cells, although capable of producing these four cyclooxy-genase end products, responded to AVP and AII stimulation with a preferential increase of PGE2, which suggests an intraglomerular feedback system between constrictor and dilator factors. Whole glomeruli, when incubated in AII, decreased in size, with a maximum decrement of surface area at 10(-10) M AII. In these glomerular contraction studies, preincubation with either arachidonate or PGE2 decreased the contractile response to AII, whereas PG inhibition enhanced the glomerular contractile response. Stable endoperoxide analogs also contracted glomeruli. In the acute phase of nephrotoxic serum nephritis (NSN) there were marked increments in glomerular production of TxA2, which correlated temporally with decrements of GFR and filtration fraction. Inhibition of TxA2 synthesis normalized GFR and filtration fraction 1-3 h after induction of NSN. These studies suggest not only an important physiological feedback role of vasodilatory PGs, as modulators of AII-induced glomerular contraction, but also a direct mesangial contractile effect of the arachidonate metabolite TxA2.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000502:physiology*; D002478:Cells, Cultured; D007678:Kidney Glomerulus / Q000502:physiology*; D009393:Nephritis / Q000503:physiopathology; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D013931:Thromboxanes / Q000096:biosynthesis*
D001095:Arachidonic Acids; D011453:Prostaglandins; D013931:Thromboxanes; D000804:Angiotensin II; D016718:Arachidonic Acid