T: Thromboxane and vascular smooth muscle cell growth in genetically hypertensive rats. Hypertension 1988;12:46—51

SUMMARY The vascular wall has the capacity to produce thromboxane A2. However, the role of vascular thromboxane A2 is still uncertain. In this study, we examined the relationship between vascular thromboxane A2 generation and vascular smooth muscle cell growth in spontaneously hypertensive rats (SHR). Vascular thromboxane A2 generation was significantly enhanced by 49 % in 5-week-old and by 117 % in 15-week-old SHR as compared with age-matched Wistar-Kyoto rats (WKY). Thromboxane A2 generation was also significantly enhanced by 59 % hi the cultured vascular smooth muscle cells of SHR when compared with production in WKY. Vascular smooth muscle cells of SHR exhibited a significantly shortened doubling time (by 32%) and greater [3H]thymldlne uptake (by 56%), as compared with those of WKY. OKY 046 (10"! M), a thromboxane synthase inhibitor, significantly tempered the rapid vascular smooth muscle cell growth hi SHR by 9 % for doubling time and by 10 % for [3H]thymidine uptake. OKY 046 did not Influence the doubling time of WKY. Conversely, a stable analogue of thromboxane A2 dose-dependently stimulated the [3H]thymidine uptake by vascular smooth muscle cells of WKY, and, at a concentration of 10" ' M, shortened the doubling time of vascular smooth muscle cells of WKY by 11%, whereas it showed slight effects on SHR. These data indicate that vascular thromboxane A2 is involved hi the regulatory mechanism of vascular smooth muscle cell growth and that enhanced vascular thromboxan