Altered aortic production of 6-keto-prostaglandin F1 alpha from aldosterone-salt hypertensive rats.

Supersensitivity of vascular smooth muscle to catecholamines in aldosterone-salt hypertensive rats appears to reside beyond the alpha 1-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 F1 alpha (6-keto-PGF1 alpha), thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) by the aortae of CSR. Production was an alpha 1-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-PGF1 alpha and TXB2, but were higher in AHR compared with CSR for PGE2. The norepinephrine concentration-response curve for 6-keto-PGF1 alpha was shifted significantly to the right for the AHR group compared with CSR (EC50 = 2.30 +/- 0.55 and 0.29 +/- 0.07 microM, 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 TXB2 and 6-keto-PGF1 alpha 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.