Increased proliferation fate and phosphoinositide turnover in cultured smooth muscle cells from spontaneously hypertensive rats.

We cultured smooth muscle cells from matched sections of thoracic aortas of 20-week-old, male, spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats and compared their rates of proliferation and phosphoinositide metabolism. After seeding at initially identical densities, smooth muscle cells from SHR grow at significantly faster (P less than 0.001) rates than those from WKY rats, so that after 10 days in culture, the cell density of SHR-derived cells (3.10 +/- 0.32 x 10(5) cells/cm2) was double that of WKY-derived cells (1.59 +/- 0.28 x 10(5) cells/cm2). Following prolonged steady-state labelling in culture, incorporation of [3H]-myo-inositol into phosphatidylinositolbiphosphate (PIP2) was greater (P less than 0.01) in SHR smooth muscle cells (10.3 +/- 1.4%) than in those from WKY (6.9 +/- 1.4%). Incorporation of [3H]-myo-inositol into inositol triphosphate was also increased (P less than 0.01) in SHR (20.2 +/- 7.3%) relative to WKY cells (11.5 +/- 5.2%), while that into glycerophosphoinositol was lower (P less than 0.01) in SHR (46.5 +/- 8.0%) than in WKY (51.3 +/- 7.8%). Enhanced smooth muscle cell growth and altered phosphoinositide metabolism may be causally or consequentially involved in enhanced vasoconstriction and vascular hypertrophy in SHR.