CHANGES IN VASCULAR WALL PRODUCTION OF PROSTACYCLIN AND THROMBOXANE A₂ IN SPONTANEOUSLY HYPERTENSIVE RATS DURING MATURATION AND THE CONCOMITANT DEVELOPMENT OF HYPERTENSION

Abstract

The purpose of this study was to clarify how the metabolism of vascular prostacyclin (PGI₂) and thromboxane (TX) A₂ in spontaneously hypertensive rats (SHR) is involved in aging and development of hypertension. We removed the aortic walls from 5-week-old and 20 to 25-week-old SHR and age-matched Wistar Kyoto rats (WKY). At 5 weeks of age, there was no significant difference in basal and maximal (arachidonic acid 0.1mM) 6-keto-PGF_1α Production between SHR and WKY, but the TXB₂ generation in the SHR aortic wall was markedly enhanced as compared with that in WKY. At 20 to 25 weeks of age, the SHR aortic wall synthesized about I .5 times more 6-keto-PGF_1α In the basal condition and twice as much as in the maximal condition as did the WKY wall. However there was no significant difference in TXB₂ production between SHR and WKY. Age-dependent increase of vascular 6-keto-PGF_1α was greater in SHR than in WKY. Moreover, the maximal/basal 6-keto-PGF_1α Production ratio increased with age in SHR, but not in WKY. The synthesis of vascular TXB₂ was enhanced with age in WKY, but did not change with age in SHR. These data suggest that not only the enhanced basal generation of vascular 6-keto PGF_1α but also a much greater reservoir of 6-keto-PGF_1α Synthesis in SHR was induced by both hypertension and maturity. The increased production of vascular TXB₂ in young SHR may affect the development of hypertension.