PRODUCTION OF EICOSANOIDS AND ANGIOTENSIN-II IN RESISTANCE VESSELS INSPONTANEOUSLY HYPERTENSIVE RATS

1. Angiotensin II (AngII) and eicosanoids may be important in vascular remodelling and the presser response via autocrine and paracrine mech anisms. We evaluated the influences of ageing and beta-adrenoceptor st imulation on the production of vascular AngII and eicosanoids in male spontaneously hypertensive rats (SHR), aged 5, 17 and 30 weeks, and ag e-matched Wistar-Kyoto (WKY) rats. 2. All rats were weighed and their systolic blood pressure (SBP) was measured by the tail-cuff method. Me senteric arteries were isolated and perfused with Krebs'-Henseleit sol ution, The outflows of prostaglandin E-2 (PGE(2)), 6-keto-PGF(1 alpha) , thromboxane B-2 (TxB(2)) and AngII were measured by specific radioim munoassays, 3. The SEP was higher in SHR than in WKY rats in the 17-an d 30-week-old groups and increased with age. Basal levels of PGE(2) we re significantly lower in SHR than in WKY rats. The ratios of 6-keto-P GF(1 alpha), to TxB(2) and PGE(2) to TxB(2) were significantly lower i n 17-week-old SHR compared with age-matched WKY rats. Basal AngIl rele ase did not differ between SHR and WKY rats and decreased with age. Is oproterenol stimulated the release of AngII; the magnitude of the incr ement was greater in WKY rats than in age-matched SHR, These results s how that there is an imbalance in the production of vasodilator and va soconstrictor eicosanoids in the resistance vessels of SHR at ages at which hypertension developed. 4. This imbalance may contribute to the increased vasoconstrictor response and vascular remodelling in SHR, Ou r findings suggest that vascular AngII plays a role in the ageing proc ess and that beta-adrenoceptor-stimulated release of vascular AngII is impaired in SHR.