Altered Aortic Production of 6-Keto-Prostaglandin F _1αfrom Aldosterone-Salt Hypertensive Rats

Abstract

Supersensitivity of vascular smooth muscle to catecholamines in aldosterone-salt hypertensive rats appears to reside beyond the α₁-adrenoceptor. The objective of this study was to assess the norepinephrine-stimulated production of arachidonic acid metabolites by aorta from control-salt rats (CSR) and aldosterone-salt hypertensive rats (AHR) to determine whether these metabolites might contribute to the altered sensitivity. Norepinephrine increased in a time-dependent manner the production of 6-keto-prostaglandin F α₁ (6-keto-PGF α₁), thromboxane B₂ (TXB₂) and prostaglandin E₂ (PGE₂) by the aortae of CSR. Production was an α₁-adrenoceptor-mediated event since it was inhibited greatly by prazosin but not by yohimbine. Basal values of the metabolites did not differ for 6-keto-PGF α₁ and TXB₂, but were higher in AHR compared with CSR for PGE₂. The norepinephrine concentration-response curve for 6-keto-PGF α₁ was shifted significantly to the right for the AHR group compared with CSR (EC₅₀ = 2.30 + 0.55 and 0.29 ± 0.07 µ M, respectively) indicating decreased production of norepinephrine-stimulated prostaglandin I₂ in AHR. The norepinephrine-stimulated TXB₂ concentration-response curves for AHR and CSR were similar. Indomethacin was an effective inhibitor of TXB₂and 6-keto-PGF ₁α production in both. Norepinephrine-stimulated contraction was significantly affected by indomethacin in CSR but not in AHR. Whereas we observed an attenuation of a norepinephrine-stimulated vasodilatory substance in aortae of AHR compared with CSR, the effect of attenuation on vascular activity is presently unclear.