SOMATOSTATIN ANTAGONIZES ANGIOTENSIN-II EFFECTS ON MESANGIAL CELL CONTRACTION AND GLOMERULAR-FILTRATION

The effects of somatostatin (ST) on the regulation of the glomerular filtration rate have not been extensively studied. The present experiments were designed to analyze this possible relationship. ST alone did not modify the planar cell surface area (PCSA) of cultured rat mesangial cells (CRMC), but it prevented and reversed the reduction in PCSA induced by 10 nm angiotensin II (Ang II) in a dose- and time-dependent manner. ST (1 mum) completely prevented and reversed the increase in the myosin light chain phosphorylation induced by 10 nm Ang II. Incubation with pertussis toxin (PT, 0.5 mug/ml) inhibited the effect of ST on the Ang II-dependent changes in PCSA, but this effect was not inhibited by the blockade of the vasodilatatory prostaglandins (indomethacin, 10 mum) or nitric oxide (L-N-methyl-arginine, 0.2 mm) synthesis. 2',5'-dideoxyadenosine (DDA, 0.1 mm), an adenylate cyclase blocker, and methylene blue (MB, 30 mum), a soluble guanylate cyclase blocker, did not interfere with the ST inhibitory effect on the Ang II-dependent reduction in PCSA of rat mesangial cells. ST also blocked the reduction in PCSA induced by phorbol myristate acetate (PMA, 300 nm). ST was also able to prevent and revert the Ang II dependent reduction in glomerular cross-sectional area of isolated rat glomeruli, also in a dose- and time-dependent fashion. Finally, intravenous administration of ST (200 ng/kg body wt as a bolus plus a continuous injection of 25 ng/min/kg body wt) partially blocked the reduction in GFR (measured as C(In)) and RPF (measured as C(PAH)) and the increase in filtration fraction induced by the intravenous administration of Ang II (1.7 mug/min/kg body wt) in anesthetized rats. In summary, these results suggest that ST could antagonize the renal actions of Ang II, increasing the GFR and RPF decreased by Ang II, and this effect could be dependent, at least partially, on a direct relaxing effect of ST on mesangial cells.