Angiotensin II mediates cell hypertrophy in vascular smooth muscle cultures from hypertensive Ren-2 transgenic rats by an amiloride- and furosemide-sensitive mechanism.
We have reported that cultured vascular smooth muscle cells (VSMC) from hypertensive Ren-2 transgenic rats (TGR) are constitutively hypertrophic when compared to matched cells from normotensive Sprague-Dawley rats (SD), by a mechanism involving the endogenous production of angiotensin II (AII). In the present work, we analyzed the possible involvement of two Na+ transport mechanisms in TGR-VSMC hypertrophy. In both SD- and TGR-VSMC, AII increased both cell size, by a furosemide- and amiloride-sensitive mechanism, and Na+/K+/2Cl- cotransport activity, by an amiloride-sensitive mechanism. Under basal unstimulated conditions, TGR-VSMC showed higher cell size and Na+/K+/2Cl- cotransport activity than SD-VSMC. Under these same conditions, losartan, furosemide, or amiloride reduced cell size only in TGR-VSMC. Similarly, basal cotransport activity was reduced by losartan and amiloride to levels similar to those observed in SD-VSMC. We conclude that hypertrophy of TGR-VSMC is dependent on the endogenous production of AII and mediated by increased Na(+)-H+ exchange and Na+/K+/2Cl- cotransport activities.
Peiró
C
C
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
Angulo
J
J
Llergo
J L
JL
Rodríguez-Mañas
L
L
Marín
J
J
Sánchez-Ferrer
C F
CF
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D001692:Biological Transport / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D005263:Femoral Artery; D005665:Furosemide / Q000494:pharmacology; D006579:Heterozygote; D006973:Hypertension / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D006984:Hypertrophy; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000096:biosynthesis / Q000235:genetics*; D012413:Rubidium / Q000378:metabolism
D000804:Angiotensin II; D010042:Ouabain; D005665:Furosemide; D012083:Renin; D012413:Rubidium