Endogenous angiotensin II and cell hypertrophy in vascular smooth muscle cultures from hypertensive Ren-2 transgenic rats.
We investigated the possible role of a tissular renin-angiotensin system in promoting the growth of vascular smooth muscle cells (VSMCs) from hypertensive transgenic rats (TGRs) with the mouse renin gene Ren-2. Mean arterial pressure values were 99.4 +/- 2.8 and 186.7 +/- 5.0 mm Hg for control Sprague-Dawley rats (SDs) and TGRs, respectively (p < 0.05). The tunica media of femoral arteries obtained from hypertensive TGRs was found to be thickened compared to that of age-matched normotensive SDs. Angiotensin II could be detected by dot blot and immunocytochemistry and quantified by radioimmunoassay in transgenic VSMCs, but not in control SD ones. Under serum-free conditions, VSMCs derived from TGRs showed a higher protein content than those derived from SDs (337 +/- 19 vs. 269 +/- 14 pg/cell, p < 0.05, n = 3). Under the same basal conditions, the mean planar cell surface area was significantly higher in TGR VSMCs than in SD ones (4,764 +/- 204 vs. 4,074 +/- 238 micron 2, p < 0.05). In addition, TGR VSMCs showed an enhanced [14C]-leucine uptake but SD VSMCs did not (13,188 +/- 663 vs. 7,633 +/- 713 dpm/well, p < 0.05). VSMCs showed a concentration-dependent proliferative response to fetal calf serum (FCS) that was more marked in TGRs than in SDs. In the absence of FCS, c-fos and c-jun mRNAs were expressed only in transgenic cultures. From the present results, we can hypothesize that cultured TGR VSMCs are able to synthesize angiotensin II that, being almost exclusive into the cells, contributes to produce VSMC growth in the absence of FCS stimulation.
Peiró
C
C
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, España.
Rodríguez-López
A M
AM
Angulo
J
J
Regadera
J
J
Marín
J
J
Sánchez-Ferrer
C F
CF
López-Novoa
J M
JM
D000804:Angiotensin II / Q000032:analysis*; D000818:Animals; D030801:Animals, Genetically Modified; D001794:Blood Pressure / Q000502:physiology; D002455:Cell Division; D048429:Cell Size; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005263:Femoral Artery; D005786:Gene Expression Regulation; D016762:Genes, fos; D016758:Genes, jun; D006973:Hypertension / Q000378:metabolism / Q000473:pathology*; D006984:Hypertrophy; D007150:Immunohistochemistry; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000235:genetics*; D017540:Tunica Media / Q000473:pathology
D000804:Angiotensin II; D012083:Renin