PRODUCTION OF EICOSANOIDS AND ANGIOTENSIN II IN RESISTANCE VESSELS IN SPONTANEOUSLY HYPERTENSIVE RATS

SUMMARY 1. Angiotensin II (Angll) and eicosanoids may be important in vascular remodelling and the pressor response via autocrine and paracrine mechanisms. We evaluated the influences of ageing and β‐adrenoceptor stimulation on the production of vascular Angll and eicosanoids in male spontaneously hypertensive rats (SHR), aged 5,17 and 30 weeks, and age‐matched Wistar‐Kyoto (WKY) rats. 2. All rats were weighed and their systolic blood pressure (SBP) was measured by the tail‐cuff method. Mesenteric arteries were isolated and perfused with Krebs'‐Henseleit solution. The outflows of prostaglandin E2 (PGE2), 6‐keto‐PGF1α, thromboxane B2 (TxB2) and AngII were measured by specific radioimmunoassays. 3. The SBP was higher in SHR than in WKY rats in the 17‐and 30‐week‐old groups and increased with age. Basal levels of PGE2 were significantly lower in SHR than in WKY rats. The ratios of 6‐keto‐PGF1α to TxB2 and PGE2 to TxB2 were significantly lower in 17‐week‐old SHR compared with age‐matched WKY rats. Basal Angll release did not differ between SHR and WKY rats and decreased with age. Isoproterenol stimulated the release of Angll; the magnitude of the increment was greater in WKY rats than in age‐matched SHR. These results show that there is an imbalance in the production of vasodilator and vasoconstrictor 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. Our findings suggest that vascular Angll plays a role in the ageing process and that β‐adrenoceptor‐stimuIated release of vascular Angll is impaired in SHR.