TERTATOLOL - A BETA-BLOCKER WITH UNIQUE EFFECTS ON HUMAN GLOMERULAR CELL-FUNCTION

Tertatolol is a beta-blocker with unique renal vasodilatatory effects, mainly at the level of the microcirculation. Since many vasodilatory agents inhibit human mesangial cell (HMC) proliferation, the effects o f tertatolol on the incorporation of H-3-thymidine in HMC were studied . Tertatolol plus mitogens (either fetal calf serum, platelet-derived growth factor (PDGF) or bovine thrombin) were incubated with HMC for 2 8 h, and H-3-thymidine was added during the last 4 h. Trichloroacetic acid-precipitable counts per well were divided by the mean number of c ells in representative wells from the same experiment. The effect of t ertatolol on angiotensin Il (10(-6) mmol/l)-induced HMC contraction wa s also assessed by measuring the planar surface area of individual cel ls. In serum-free media, tertatolol did not significantly alter the in corporation of H-3-thymidine after 28 h of incubation in HMC. When ter tatolol was added in the presence of 1 % serum, H-3-thymidine incorpor ation was significantly reduced, compared to 1 % serum alone. Tertatol ol also inhibited 3H incorporation when PDGF and thrombin were used as the stimulus. The increase in cell number normally seen after 7 days in serum was also reduced by tertatolol. Tertatolol inhibited the redu ction in planar surface area of HMC induced by angiotensin II. The inh ibitory effect of tertatolol on HMC proliferation was also potentiated by ritanserin and MDL 72222, 5HT2 and 5HT3 antagonists, respectively. Conversely, the 5HT1A agonist 8-OH-DPAT did not modify the H-3-thymid ine incorporation in HMC in the presence of tertatolol. In conclusion, tertatolol inhibits HMC proliferation. The mechanism cannot be explai ned by beta-blockade or stimulation of 5-HT1A receptors, and still rem ains unclear.