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 of tertatolol on the incorporation of 3H-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 28 h, and 3H-thymidine was added during the last 4 h. Trichloroacetic acid-precipitable counts per well were divided by the mean number of cells in representative wells from the same experiment. The effect of tertatolol on angiotensin II (10(-6) mmol/l)-induced HMC contraction was also assessed by measuring the planar surface area of individual cells. In serum-free media, tertatolol did not significantly alter the incorporation of 3H-thymidine after 28 h of incubation in HMC. When tertatolol was added in the presence of 1% serum, 3H-thymidine incorporation was significantly reduced, compared to 1% serum alone. Tertatolol 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 reduction in planar surface area of HMC induced by angiotensin II. The inhibitory 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 3H-thymidine incorporation in HMC in the presence of tertatolol. In conclusion, tertatolol inhibits HMC proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
Shultz
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P
Renal Section (IIIJ), VA Medical Center, Minneapolis, Minn 55417.
Raij
L
L
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D011412:Propanolamines / Q000494:pharmacology*; D013876:Thiophenes
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D011412:Propanolamines; D013876:Thiophenes; C005632:tertatolol