Glomerular mesangial cell contractility in vitro is controlled by an angiotensin-prostaglandin balance.
Rat renal mesangial cells possess morphological and functional features of smooth muscle cells in culture, such as intracellular myosin filaments, A II receptors and a contractile response to A II. Furthermore, they represent the main glomerular site of PGE2 synthesis. In the presence of A II (50 nM), their PGE2 production rate was significantly increased, this effect being potentiated by arachidonic acid (3 micrograms/ml). After a prior inhibition of arachidonic acid metabolism by cyclooxygenase inhibitors (indomethacin 1 microM or naproxen 0.02 microM) or by a cyclo- and lipoxygenase inhibitor (phenidone 670 microM), the percentage of cells contracting in response to various A II concentrations (10 pM to 10 nM) was significantly enhanced as compared to the basal conditions. On the contrary, the percentage of cells presenting a contractile response to A II in the presence of exogenous PGE2 (50 ng/ml) or of arachidonic acid (3 micrograms/ml) was significantly decreased. These modifications were not related to some changes in the A II receptor properties of the cells, i.e. the number of receptor sites and their affinity constant. The data demonstrate that the contractile response of glomerular mesangial cells is modulated by the PGE2 content of their incubation medium. Since their own PGE2 production rate is enhanced in the presence of A II, this cellular response may represent a local regulatory mechanism of their contractile properties.
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000166:cytology*; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D008858:Microscopy, Phase-Contrast; D009288:Naproxen / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D011458:Prostaglandins E / Q000096:biosynthesis; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; D011458:Prostaglandins E; D011720:Pyrazoles; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D016718:Arachidonic Acid; D009288:Naproxen; C015429:phenidone; D015232:Dinoprostone; D007213:Indomethacin