Effects of loop diuretics on angiotensin II-stimulated vascular smooth muscle cell growth.
BACKGROUND
Torasemide and furosemide are diuretics that inhibit the Na(+), K(+), 2Cl(-) co-transporter localized in cells from the ascending limb of the loop of Henle. The effects of torasemide and furosemide on cell growth induced by angiotensin II (Ang II) were investigated in cultured vascular smooth muscle cells (VSMCs) obtained from the aorta of adult spontaneously hypertensive rats (SHR).


METHODS
Cell growth was determined by DNA and protein synthesis as measured by [3H]thymidine and [3H]leucine incorporation, respectively. Proliferation of VSMCs was measured using a non-radioactive colorimetric cell proliferation assay.


RESULTS
Ang II (10(-7) M) signficantly increased DNA and protein synthesis and cell proliferation in VSMCS: These effects were completely abolished by the Ang II type 1 receptor antagonist irbesartan (10(-6) M). Ang II-induced [3H]leucine incorporation was reduced in a dose-dependent way by torasemide (IC(50) value: 7.7+/-0.8x10(-7) M) but not by furosemide. Neither torasemide nor furosemide modified Ang II-stimulated [3H]thymidine incorporation or proliferation in VSMCs.


CONCLUSIONS
These results indicate that torasemide, but not furosemide, inhibits Ang II-induced protein synthesis in VSMCs from SHR. Thus, it is suggested that the capacity of torasemide to block this trophic action of Ang II in rat VSMCs is not mediated by inhibition of the Na(+), K(+), 2Cl(-) co-transport mechanism.
Muñiz
P
P
Division of Cardiovascular Pathophysiology, School of Medicine, University of Navarra, Pamplona, Spain.
Fortuño
A
A
Zalba
G
G
Fortuño
M A
MA
Díez
J
J
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology*; D005665:Furosemide / Q000494:pharmacology*; D000077405:Irbesartan; D007930:Leucine / Q000378:metabolism; D008138:Loop of Henle / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012964:Sodium / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters; D013449:Sulfonamides / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D000077786:Torsemide
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D002352:Carrier Proteins; D002712:Chlorides; D004232:Diuretics; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D028021:Sodium-Potassium-Chloride Symporters; D013449:Sulfonamides; D013777:Tetrazoles; D000804:Angiotensin II; D005665:Furosemide; D012964:Sodium; D007930:Leucine; D000077405:Irbesartan; D011188:Potassium; D013936:Thymidine; D000077786:Torsemide